Peroksinitrit literasi
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eroxynitrite-induced membrane lipid peroxidation: the cytotoxicpotential of superoxide and nitric oxide.Radi R, Beckman JS, Bush KM, Freeman BA.
Source
Department of Anesthesiology, ni!ersity of Ala"ama, Birmingham #$%##.
A"stract
&ndothelial cells, macrophages, neutrophils, and neuronal cells generate supero'ide
()%*+ and nitric o'ide (.)+ -hich can com"ine to form pero'ynitrite anion ()))*+.
ero'ynitrite, kno-n to o'idi/e sulfhydryls and to yield products indicati!e of hydro'yl
radical (.)0+ reaction -ith deo'yri"ose and dimethyl sulfo'ide, is sho-n herein to induce
mem"rane lipid pero'idation. ero'ynitrite addition to soy"ean phosphatidylcholine
liposomes resulted in malondialdehyde and con1ugated diene formation, as -ell as
o'ygen consumption. 2ipid pero'idation -as greater at acidic and neutral p0, -ith no
significant lipid pero'idation occurring a"o!e p0 3.$. Addition of ferrous (Fe4%+ or ferric
(Fe4#+ iron did not enhance lipid pero'ide formation o!er that attri"uta"le to pero'ynitrite
alone. Diethylenetetraminepentacetic acid (D5A+ or iron remo!al from solutions "y ion*
e'change chromatography decreased con1ugated diene formation "y %$*$67. 8ron did
not play an essential role in initiating lipid pero'idation, since D5A and iron depletion of
reaction systems -ere only partially inhi"itory. 8n contrast, desferrio'amine had an e!en
greater concentration*dependent inhi"itory effect, completely a"olishing lipid
pero'idation at %66 microM. 5he strong inhi"itory effect of desferrio'amine on lipid
pero'idation -as due to direct reaction -ith pero'ynitrous acid in addition to iron
chelation. 9e conclude that the con1ugate acid of pero'ynitrite, pero'ynitrous acid()))0+, and:or its decomposition products, i.e., .)0 and nitrogen dio'ide (.)%+,
initiate lipid pero'idation -ithout the re;uirement of iron. 5hese o"ser!ations
demonstrate a potential mechanism contri"uting to )%*(*+and .)*mediated cytoto'icity.
eroxynitrite-mediated protein nitration and lipidperoxidation in a mouse model of traumatic brain injury .0all &D, Detloff MR, Johnson K, Kupina
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5he role of reacti!e o'ygen*induced o'idati!e damage to lipids (i.e., lipid pero'idation,
2+ and proteins has "een strongly supported in pre!ious -ork. Most nota"ly, a num"er
of free radical sca!engers and lipid antio'idants ha!e "een demonstrated to "e
neuroprotecti!e in traumatic "rain in1ury (5B8+ models. 0o-e!er, the specific sources of
reacti!e o'ygen species (R)S+, the time course of o'idati!e damage and its relationship
to post*traumatic neurodegeneration in the in1ured "rain ha!e "een incompletely defined.5he present study -as directed at an in!estigation of the role of the R)S, pero'ynitrite
()+, in the acute pathophysiology of 5B8 and its temporal relationship to
neurodegeneration in the conte't of the mouse model of diffuse head in1ury model. Male
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administration on diaphragmatic force*generating capacity in @+ intact diaphragm muscle
fi"er "undles (to model the effects produced "y e'posure of muscles to e'tracellular
pero'ynitrite+ and %+ single skinned diaphragm muscle fi"ers (to model the effects of
intracellular pero'ynitrite on contractile protein function+ "y e'amining the effects of "oth
pero'ynitrite and a pero'ynitrite*generating solution, #*morpholinosydnonimine, on force
!s. p
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0ydrogen pero'ide is generated in numerous "iological processes and is implicated as
the main transmitter of redo' signals. Although a strong o'idant, high acti!ation energy
"arriers make it unreacti!e -ith most "iological molecules. 8t reacts directly -ith thiols,
"ut for lo-*molecular*-eight thiols and cysteine residues in most proteins, the reaction is
slo-. 5he most fa!ored reactions of hydrogen pero'ide are -ith transition metal centers,
selenoproteins, and selected thiol proteins. 5hese include proteins such as catalase,glutathione pero'idases, and pero'iredo'ins, -hich, as -ell as pro!iding antio'idant
defense, are increasingly "eing considered as targets for signal transmission. 5his
o!er!ie- descri"es the main "iological reactions of hydrogen pero'ide and takes a
kinetic approach to identifying likely targets in the cell. 8t also considers diffusion of
hydrogen pero'ide and constraints to its acting at locali/ed sites.
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