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Transcript of Radiation Protection: Radiation Toxicology: neuraminidase enzymes, neuraminidase inhibitors.
RADIATION PROTECTION RADIATION TOXICOLOGY NEURAMINIDASE ENZYMES NEURAMINIDASE INHIBITORS
DMITRI POPOV MD (RUSSIA) PHD RADIOBIOLOGYADVANCED MEDICAL TECHNOLOGY AND SYSTEMS INC CANADA
RADIATION TOXICOLOGY
bull Radiation Protection Radiation Toxicology neuraminidase enzymes neuraminidase inhibitorsbull Dmitri Popovbull Full-text Research Proposal middot Feb 2016bull Add resourcesbull File name RadiationToxicologyNeuroamidazepptx
DOI 1013140RG221439336962
NEURAMINIDASE HTTPSENWIKIPEDIAORGWIKINEURAMINIDASEbull Neuraminidase enzymes are glycoside hydrolase enzymes (EC 32118)
that cleave the glycosidic linkages of neuraminic acids Neuraminidase enzymes are a large family found in a range of organisms The best-known neuraminidase is the viral neuraminidase a drug target for the prevention of the spread of influenza infection The viral neuraminidases are frequently used as antigenic determinants found on the surface of the Influenza virus Some variants of the influenza neuraminidase confer more virulence to the virus than others Other homologs are found in mammalian cells which have a range of functions bull At least four mammalian sialidase homologs have been described in the
human genome (see NEU1 NEU2 NEU3 NEU4)
NEURAMINIDASE
bull There are two major classes of Neuraminidase that cleave exo or endo poly-sialic acidsbull Exo hydrolysis of α-(2rarr3)- α-(2rarr6)- α-(2rarr8)-glycosidic
linkages of terminal sialic acid residues
bull Endo hydrolysis of (2rarr8)-α-sialosyl linkages in oligo- or poly(sialic) acids[2]
NEURAMINIDASE
bull Schauer R (1982) Chemistry metabolism and biological functions of sialic acids Adv Carbohydr Chem Biochem Advances in Carbohydrate Chemistry and Biochemistry 40 131ndash234 doi101016S0065-2318(08)60109-2 ISBN 978-0-12-007240-8PMID 6762816
NEURAMINIDASE
bull Cabezas JA (August 1991) Some questions and suggestions on the type references of the official nomenclature (IUB) for sialidase(s) and endosialidase Biochem J 278 (Pt 1) 311ndash2 doi101042bj2780311
NEURAMINIDAZE
bull Sialidase 1 (lysosomal sialidase) also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene
NEURAMINIDASE
bull The protein encoded by this gene encodes the lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids In the lysosome this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as protective protein) Mutations in this gene can lead tosialidosis[3]
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
RADIATION TOXICOLOGY
bull Radiation Protection Radiation Toxicology neuraminidase enzymes neuraminidase inhibitorsbull Dmitri Popovbull Full-text Research Proposal middot Feb 2016bull Add resourcesbull File name RadiationToxicologyNeuroamidazepptx
DOI 1013140RG221439336962
NEURAMINIDASE HTTPSENWIKIPEDIAORGWIKINEURAMINIDASEbull Neuraminidase enzymes are glycoside hydrolase enzymes (EC 32118)
that cleave the glycosidic linkages of neuraminic acids Neuraminidase enzymes are a large family found in a range of organisms The best-known neuraminidase is the viral neuraminidase a drug target for the prevention of the spread of influenza infection The viral neuraminidases are frequently used as antigenic determinants found on the surface of the Influenza virus Some variants of the influenza neuraminidase confer more virulence to the virus than others Other homologs are found in mammalian cells which have a range of functions bull At least four mammalian sialidase homologs have been described in the
human genome (see NEU1 NEU2 NEU3 NEU4)
NEURAMINIDASE
bull There are two major classes of Neuraminidase that cleave exo or endo poly-sialic acidsbull Exo hydrolysis of α-(2rarr3)- α-(2rarr6)- α-(2rarr8)-glycosidic
linkages of terminal sialic acid residues
bull Endo hydrolysis of (2rarr8)-α-sialosyl linkages in oligo- or poly(sialic) acids[2]
NEURAMINIDASE
bull Schauer R (1982) Chemistry metabolism and biological functions of sialic acids Adv Carbohydr Chem Biochem Advances in Carbohydrate Chemistry and Biochemistry 40 131ndash234 doi101016S0065-2318(08)60109-2 ISBN 978-0-12-007240-8PMID 6762816
NEURAMINIDASE
bull Cabezas JA (August 1991) Some questions and suggestions on the type references of the official nomenclature (IUB) for sialidase(s) and endosialidase Biochem J 278 (Pt 1) 311ndash2 doi101042bj2780311
NEURAMINIDAZE
bull Sialidase 1 (lysosomal sialidase) also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene
NEURAMINIDASE
bull The protein encoded by this gene encodes the lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids In the lysosome this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as protective protein) Mutations in this gene can lead tosialidosis[3]
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASE HTTPSENWIKIPEDIAORGWIKINEURAMINIDASEbull Neuraminidase enzymes are glycoside hydrolase enzymes (EC 32118)
that cleave the glycosidic linkages of neuraminic acids Neuraminidase enzymes are a large family found in a range of organisms The best-known neuraminidase is the viral neuraminidase a drug target for the prevention of the spread of influenza infection The viral neuraminidases are frequently used as antigenic determinants found on the surface of the Influenza virus Some variants of the influenza neuraminidase confer more virulence to the virus than others Other homologs are found in mammalian cells which have a range of functions bull At least four mammalian sialidase homologs have been described in the
human genome (see NEU1 NEU2 NEU3 NEU4)
NEURAMINIDASE
bull There are two major classes of Neuraminidase that cleave exo or endo poly-sialic acidsbull Exo hydrolysis of α-(2rarr3)- α-(2rarr6)- α-(2rarr8)-glycosidic
linkages of terminal sialic acid residues
bull Endo hydrolysis of (2rarr8)-α-sialosyl linkages in oligo- or poly(sialic) acids[2]
NEURAMINIDASE
bull Schauer R (1982) Chemistry metabolism and biological functions of sialic acids Adv Carbohydr Chem Biochem Advances in Carbohydrate Chemistry and Biochemistry 40 131ndash234 doi101016S0065-2318(08)60109-2 ISBN 978-0-12-007240-8PMID 6762816
NEURAMINIDASE
bull Cabezas JA (August 1991) Some questions and suggestions on the type references of the official nomenclature (IUB) for sialidase(s) and endosialidase Biochem J 278 (Pt 1) 311ndash2 doi101042bj2780311
NEURAMINIDAZE
bull Sialidase 1 (lysosomal sialidase) also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene
NEURAMINIDASE
bull The protein encoded by this gene encodes the lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids In the lysosome this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as protective protein) Mutations in this gene can lead tosialidosis[3]
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASE
bull There are two major classes of Neuraminidase that cleave exo or endo poly-sialic acidsbull Exo hydrolysis of α-(2rarr3)- α-(2rarr6)- α-(2rarr8)-glycosidic
linkages of terminal sialic acid residues
bull Endo hydrolysis of (2rarr8)-α-sialosyl linkages in oligo- or poly(sialic) acids[2]
NEURAMINIDASE
bull Schauer R (1982) Chemistry metabolism and biological functions of sialic acids Adv Carbohydr Chem Biochem Advances in Carbohydrate Chemistry and Biochemistry 40 131ndash234 doi101016S0065-2318(08)60109-2 ISBN 978-0-12-007240-8PMID 6762816
NEURAMINIDASE
bull Cabezas JA (August 1991) Some questions and suggestions on the type references of the official nomenclature (IUB) for sialidase(s) and endosialidase Biochem J 278 (Pt 1) 311ndash2 doi101042bj2780311
NEURAMINIDAZE
bull Sialidase 1 (lysosomal sialidase) also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene
NEURAMINIDASE
bull The protein encoded by this gene encodes the lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids In the lysosome this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as protective protein) Mutations in this gene can lead tosialidosis[3]
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASE
bull Schauer R (1982) Chemistry metabolism and biological functions of sialic acids Adv Carbohydr Chem Biochem Advances in Carbohydrate Chemistry and Biochemistry 40 131ndash234 doi101016S0065-2318(08)60109-2 ISBN 978-0-12-007240-8PMID 6762816
NEURAMINIDASE
bull Cabezas JA (August 1991) Some questions and suggestions on the type references of the official nomenclature (IUB) for sialidase(s) and endosialidase Biochem J 278 (Pt 1) 311ndash2 doi101042bj2780311
NEURAMINIDAZE
bull Sialidase 1 (lysosomal sialidase) also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene
NEURAMINIDASE
bull The protein encoded by this gene encodes the lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids In the lysosome this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as protective protein) Mutations in this gene can lead tosialidosis[3]
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASE
bull Cabezas JA (August 1991) Some questions and suggestions on the type references of the official nomenclature (IUB) for sialidase(s) and endosialidase Biochem J 278 (Pt 1) 311ndash2 doi101042bj2780311
NEURAMINIDAZE
bull Sialidase 1 (lysosomal sialidase) also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene
NEURAMINIDASE
bull The protein encoded by this gene encodes the lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids In the lysosome this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as protective protein) Mutations in this gene can lead tosialidosis[3]
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDAZE
bull Sialidase 1 (lysosomal sialidase) also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene
NEURAMINIDASE
bull The protein encoded by this gene encodes the lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids In the lysosome this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as protective protein) Mutations in this gene can lead tosialidosis[3]
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASE
bull The protein encoded by this gene encodes the lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids In the lysosome this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as protective protein) Mutations in this gene can lead tosialidosis[3]
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
bull Sialidase-2 is an enzyme that in humans is encoded by the NEU2 genebull This gene belongs to a family of glycohydrolytic enzymes
which remove sialic acid residues from glycoproteins and glycolipids Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase Its cytosolic localization was demonstrated by cell fractionation experiments
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASE
bull Sialidase-3 is an enzyme that in humans is encoded by the NEU3 gene bull This gene product belongs to a family of glycohydrolytic
enzymes which remove sialic acid residues from glycoproteins and glycolipids It is localized in the plasma membrane and its activity is specific for gangliosides It may play a role in modulating the ganglioside content of the lipid bilayer
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASE
bull This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipidsbull Sialidase-4 is an enzyme that in humans is encoded by
the NEU4 gene
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
VIRAL NEURAMINIDASE
bull Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replicationbull When influenza virus replicates it attaches to the interior cell surface using
hemagglutinin a molecule found on the surface of the virus that binds to sialic acid groups Sialic acids are found on various glycoproteins at the host cell surface and the virus exploits these groups to bind the host cell In order for the virus to be released from the cell neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
VIRAL NEURAMINIDASE
bull Since the cleavage of the sialic groups is an integral part of influenza replication blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenzabull A single hemagglutinin-neuraminidase protein can combine
neuraminidase and hemagglutinin functions such as in mumps virus and human parainfluenza virus
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
VIRAL NEURAMINIDASE
bull Hemagglutinin or haemagglutinin (British English) refers to a substance that causes red blood cells (RBCs) to agglutinate This process is called hemagglutination or haemagglutinationbull Antibodies[1] and lectins[2] are commonly known
hemagglutinins
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASE
bull Bacterial neuraminidase is type of neuraminidase and a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa Its function is to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which type 4 pilli (attachment factors) bind preferentiallybull httpsenwikipediaorgwikiBacterial_neuraminidase
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASE
bull Many respiratory pathogens including Hemophilus influenzae Streptococcus pneumoniae and Pseudomonas aeruginosa express neuraminidases that can cleave alpha23-linked sialic acids from glycoconjugates As mucosal surfaces are heavily sialylated neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASE
bull J Clin Invest 2006 Aug116(8)2297-2305bull Bacterial neuraminidase facilitates mucosal infection
by participating in biofilm productionbull Soong G1 Muir A Gomez MI Waks J Reddy B Planet P
Singh PK Kaneko Y Wolfgang MC Hsiao YS Tong L Prince A
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASES
bull Front Med (Lausanne) 2015 2 14bull Published online 2015 Mar 17 doi 103389fmed201500014bull PMCID PMC4362343bull Neuroinflammation Induced by Intracerebroventricular Injection of
Microbial Neuraminidasebull Pablo Granados-Duraacuten1 Mariacutea D Loacutepez-Aacutevalos1 Jesuacutes M Grondona1 Mariacutea
del Carmen Goacutemez-Roldaacuten1Manuel Cifuentes12 Margarita Peacuterez-Martiacuten1 Martina Alvarez3 Fernando Rodriacuteguez de Fonseca4 and Pedro Fernaacutendez-Llebrez1
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASES
bull Kelly and Greiff demonstrated in mice the high toxic effects of bacterial and viral NA when injected directly into the brain Also in humans NA activity seems to be associated with adverse prognosis in pneumococcal meningitis
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]bull 12 Kelly R Greiff D Toxicity of pneumococcal
neuraminidase Infect Immun (1970) 2115ndash7
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASES
bull OrsquoToole RD Goode L Howe C Neuraminidase activity in bacterial meningitis J Clin Invest (1971)50979ndash85101172JCI106591 bull 14 Loumlve A Rydbeck R Kristensson K Orvell C Norrby
E Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis analysis of mutants selected with monoclonal antibodies J Virol (1985) 5367ndash74
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASES
bull Finsterer J Hess B Neuromuscular and central nervous system manifestations of Clostridium perfringens infections Infection (2007) 35396ndash405101007s15010-007-6345-z
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
BACTERIAL NEURAMINIDASES
bull Kelly RT Greiff D Neuraminidase and neuraminidase-labile substrates in experimental influenza virus encephalitis Biochim Biophys Acta (1965) 110548ndash53101016S0926-6593(65)80068-6 [Cross Ref]
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor
cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma M-79 transplanted to the thigh of C3HHeJ mice When the tumors reached 4-8 mm in diameter various treatments were started X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (233) The inoculation of 1times 106of VCN-cells to the tumor-bearing animals every other day for a total of three doses caused a complete regression of 6 out of 57 tumors (105) Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (379) The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone
bull Copyright 1975 Academic Press Inc
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASES AND IMMUNOTHERAPY OF TUMORSbull Chang W Song and Seymour H Levitt (1975) Immunotherapy
with Neuraminidase-Treated Tumor Cells after Radiotherapy Radiation Research December 1975 Vol 64 No 3 pp 485-491bull Immunotherapy with Neuraminidase-Treated Tumor
Cells after Radiotherapybull Chang W Song and Seymour H Levitt
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
IMMUNOTHERAPY
bull Science 1971 Nov 5174(4009)591-3bull Immunotherapy of cancer immunospecific rejection of tumors in recipients of
neuraminidase-treated tumor cells plus BCGbull Simmons RL Rios Abull Abstractbull Firmly established methylcholanthrene fibrosarcomas in syngeneic mice will totally disappear if
the hosts are treated with living tumor cells that have been exposed to Vibrio cholerae neuraminidase in vitro The effect is magnified by the simultanieous injection of a nonspecific immunostimulant BCG The rejection of the methylcholanthrene tumor is immunospecific and can be induced only with tumor cells treated with Vibrio cholerae neuraminidase identical in type with the growing tumor
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASES
bull Biochemistry 1984 Mar 2723(7)1442-8bull Modulation of neuraminidase activity by the physical
state of phospholipid bilayers containing gangliosides Gd1a and Gt1bbull Myers M Wortman C Freire E
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
HUMAN NEURAMINIDASES
bull Lysosomal neuraminidase is present In virtually all vertebrate tissues and cell types and has been purified and characterized from many sources including placenta mammary gland brain kidney liver testis thyroid salivary gland leukocytes lymphocytes macrophages and fibroblasts
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
RADIATION AND GLYCOSYLATION
bull Biochem Biophys Res Commun 1997 Nov 17240(2)395-8bull Altered N-glycosylation of glucose transporter-1
associated with radiation-induced tumorigenesis of human cell hybridsbull Noto Y1 Iwazaki A Nagao J Sumiyama Y Redpath JL
Stanbridge EJ Kitagawa T
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
RADIATION AND GLYCOSYLATION
bull ldquoStudies on human cell hybrids between a cervical carcinoma cell line HeLa and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11 We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter GLUT1 due to altered glycosylation when compared to the nontumorigenic counterpart CGL1 In this study we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen intestinal alkaline phosphataserdquo
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
RADIATION AND GLYCOSYLATION
bull ldquoIn contrast GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration In accordance with this glycosylation change affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybridsrdquo
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
RADIATION AND GLYCOSYLATION
bull J Pharm Biomed Anal 2016 Jan 25118380-6 doi 101016jjpba201511010 Epub 2015 Nov 14bull Changes of protein glycosylation in the course of radiotherapybull Toacuteth E1 Veacutekey K2 Ozohanics O3 Jekő A3 Dominczyk I4 Widlak P4 Drahos L5bull Author informationbull Abstractbull This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing
radiation Site specific glycosylation patterns of 7 major plasma proteins were analyzed 171 glycoforms were identified and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients It was found that glycosylation of plasma proteins does change in response to partial body irradiation (sim 60 Gy) and the effects last during follow-up the abundance of some glycoforms changed more than twofold Both the degree of changes and their time-evolution showed large inter-individual variability
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
INHIBITION OF NEURAMINIDASES
bull ldquoInhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA) Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication With the use of reverse genetics technique we investigated the effect of glycans attached at Asn 94a 129 and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activityrdquo
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
INHIBITION OF NEURAMINIDASES
bull Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitorsbull Vasiliy P Mishin1dagger bull Dmitri Novikov1Dagger bull Frederick G Hayden12 andbull Larisa V Gubareva1
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIDASES
bull The two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of influenza A virus interact with cellular receptors containing terminal neuraminic acid (NeuAc) moieties HA initiates infection by binding to cellular receptors whereas NA destroys the receptors by cleaving off NeuAc moieties
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMIDASES INHIBITION
bull JOURNAL OF VIROLOGY Oct 2005 p 12416ndash12424 Vol 79 No 19 0022-538X05$08000 doi101128JVI791912416ndash124242005 Copyright copy 2005 American Society for Microbiology All Rights Reserved Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors Vasiliy P Mishin1 dagger Dmitri Novikov1 Dagger Frederick G Hayden12 and Larisa V Gubareva1 Department of Internal Medicine School of Medicine University of Virginia Charlottesville Virginia1 and Department of Pathology School of Medicine University of Virginia Charlottesville Virginia2
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIC ACID
bull Neuraminic acid (5-amino-35-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid) is a 9-carbon monosaccharide (a nonose) a derivative of a ketononose Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine (2-amino-2-deoxy-mannose) Neuraminic acid does not occur naturally but many of its derivatives are found widely distributed in animal tissues and in bacteria especially in glycoproteins and gangliosides The N- or O-substituted derivatives of neuraminic acid are collectively known as sialic acids the predominant form in mammalian cells being N-acetylneuraminic acid The amino group bears either an acetyl or a glycolyl group The hydroxyl substituents may vary considerably acetyl lactyl methyl sulfate and phosphate groups have been found
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
NEURAMINIC ACID
bull Br J Pharmacol 1978 Oct64(2)301-4bull Inhibition by N-acetyl neuraminic acid of platelet thrombogenesis induced by laser injury to
rat and hamster venulesbull Born GV Kovaacutecs IBbull Abstractbull 1 In rats and hamsters under barbiturate anaesthesia laser radiation to venules about 50 micrometer in
diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min 2 This occlusion time was significantly prolonged by the intravenous injection of N-acetyl neuraminic acid (NANA) but not by D-glucuronic acid or beta-methoxyneuraminic acid in doses which had no effect on blood pH or on the condition of the animals 3 The results confirm the anti-thrombotic effect of NANA previously demonstrated with another technique
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
CYTOTOXICITY
bull The antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell whose membrane-surface antigens have been bound by specific antibodies In humans ADCC is usually mediated by IgG[citation needed] It is one of the mechanisms through which antibodies as part of the humoral immune response can act to limit and contain infection
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
CYTOTOXICITY HEMAGGLUTININS NEURAMINIDASESbull Detection of neutralizing antibodies (nAbs) to influenza A virus
hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
CYTOTOXICITYbull The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc
receptors mostly CD16 These receptors recognize and bind to the Fc portion of an antibody such as IgG which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG the Natural Killer cell releases cytokines such as IFN-γ
bull During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next the NK cells which have Fc Receptors will bind to that antibody inducing the NK cell to release proteins such as perforin and proteases known as granzymes which causes the lysis of the infected cell to hinder the spread of the virus
bull Furthermore NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface indicating a non-self cell This is because generally all nucleated cells (which excludes RBCs) of the body contain MHC I
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
HUMAN NEURAMINIDASES AND ACUTE RADIATION SYNDROMESbull Inhibiting human neuraminidases before and after irradiation
could provide a novel mechanism to prevent Acute Radiation Syndromes
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
LITERATURE
bull httpsenwikipediaorgwikiAntibody-dependent_cell-mediated_cytotoxicitybull httpwwwjbcorgcontent2754837657fullbull httpsbooksgooglecabooks
id=2IXMBQAAQBAJamppg=PA131amplpg=PA131ampdq=peroxidases+and+lysosomal+activationampsource=blampots=VZxbVXtMfMampsig=TO2JSWMpz1ZTl8Xxi_xnhFQRofgamphl=enampsa=Xampved=0ahUKEwigtuPQi97PAhVI7SYKHdgJC-0Q6AEIRDAHv=onepageampq=peroxidases20and20lysosomal20activationampf=false
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-
LITERATURE
bull httpswwwncbinlmnihgovpmcarticlesPMC4362343bull httpswwwncbinlmnihgovpmcarticlesPMC4943536bull httpswwwncbinlmnihgovpubmed26609677
- Radiation Protection Radiation Toxicology neuraminidase enzym
- Radiation toxicology
- Neuraminidase httpsenwikipediaorgwiki Neuraminidase
- Neuraminidase
- Neuraminidase (2)
- Neuraminidase
- Neuraminidaze
- neuraminidase
- Slide 9
- Neuraminidase (3)
- Neuraminidase (2)
- Viral neuraminidase
- Viral neuraminidase (2)
- Viral neuraminidase
- Bacterial neuraminidase
- Bacterial neuraminidase (2)
- Bacterial neuraminidase
- Bacterial neuraminidases
- Bacterial neuraminidases
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (2)
- Bacterial neuraminidases (3)
- Bacterial neuraminidases (4)
- Neuraminidases and immunotherapy of tumors
- Neuraminidases and immunotherapy of tumors (2)
- Immunotherapy
- Neuraminidases
- Human neuraminidases
- Radiation and glycosylation
- Radiation and glycosylation (2)
- Radiation and glycosylation (3)
- Radiation and glycosylation (4)
- Inhibition of neuraminidases
- Inhibition of neuraminidases
- Neuraminidases (2)
- Neuramidases inhibition
- Neuraminic acid
- Neuraminic acid (2)
- cytotoxicity
- Cytotoxicity hemagglutinins neuraminidases
- cytotoxicity (2)
- Human neuraminidases and Acute radiation syndromes
- literature
- Literature
-