The role of lipid microviscosity changes in inactivation of the opioid receptors of brain synaptic...

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Abstracts / Chemistry and Physics of Lipids 149S (2007) S23–S49 S33 PO 26 The role of lipid microviscosity changes in inactivation of the opioid receptors of brain synaptic membranes Elena Maltseva , Olga Belokoneva Institute of Biochemical Physics of Russian Academy of Sciences, Russia The fluidity of membrane lipids takes part in regulation of the membrane-bound receptors. The binding activity of the opioid receptors detected by antagonist-naloxone is stabilized by unsaturated fatty acids, acidic phospho- lipids and ionol (4-methyl-2,6-ditretbutylphenol). To understand the mechanism of spontaneous inactivation of membrane-bound opioid receptors it was studied the changes of lipid microviscosity during incubation of rat brain synaptosomes (at 37 C) in the presence of various effectors such as the unsaturated fatty acids (arachidonic, palmitic and linoleic) and synthetic antioxidants—ionol and phenozan K (potassium salt of 4-hydroxy-3,5-ditret-butyl-phenylpropoinic acid).The lipid microviscosity was studied by EPR-technique on the computerized spectrometer Bruker-200D using two spin-probes: 2,2,6,6-tetra-methyl-4-capryloyl- oxipiperidine-1-oxyl(1) and 5,6-benzo-2,2,4,4-tetra- methyl-1,2,3,4-tetra-hydro-gamma-carbolin-3-oxyl(2), preferentially localized in the surface and annular membrane lipids correspondingly. The value of micro- viscosity was estimated by rotational correlation time (T c ) of spin probes using formula for fast-rotated radi- cals. It was shown that these unsaturated acids increased T c 2 during incubation time (1 h), the effect of linoleic acid is more (20%)than others; ionol and, especially, phenozan K decreased T c 2. All effectors (but not phenozan K) increased T c 1 compared with control (linoleic acid—in more extent as well); but the values of T c 1 decline exponentially during incubation in all cases. It was obtained the correlation between changes of T c 1 and rates of receptors inactivation, which can be described by an empirical equation. It was proposed that destabilization of the opioid receptors caused by increasing lipid fluidity of synaptic membranes. doi:10.1016/j.chemphyslip.2007.06.074 PO 27 Effects of Minerval on fatty acid and phospholipid composition in mice tissues and human glioma cells Maria Laura Martin , Gwendolyn Barcel´ o-Coblijn, Maria Ant ` onia Noguera, Silvia Ter´ es, Pablo V. Escrib´ a Laboratory of Molecular Cell Biomedicine, Department of Biology, Institut Universitari d’Investigaci´ o en Ci` encies de la Salut (IUNICS), University of the Balearic Islands, Spain Minerval (2-hydroxy oleic acid) is a potent antitumor drug, whose actions are related to its effects on the membrane lipid structure and the function of important membrane proteins. Changes in membrane lipid com- position alter membrane structure, protein–membrane interactions and cell signaling. In order to investigate whether Minerval treatments modify membrane lipid composition, we determined changes in phospholipid mass, phospholipid fatty acid composition, and choles- terol mass in livers, hearts and brains of mice treated with 600 mg/(kg day) of Minerval for 10 days. We also analyzed membrane lipids in human glioma cell lines (U118 and SF-767) treated with Minerval. Animals and cells treated were compared with the corresponding untreated controls. We observed that brain phospholipid composition was not significantly altered by Minerval treatment while brain cholesterol content decreased in treated mice. On the other hand, Minerval treatments induced increases in the levels of monounsaturated fatty acids, mainly C18:1. To understand the effect of Min- erval on protein function, we analyzed its effect on the localization of signaling peripheral proteins. For this pur- pose, SF-767 cells were treated with Minerval (200 M) for 1 and 24 h. Minerval induced reductions of PKC con- tent in the soluble fraction and increase in the membrane fraction, which is associated with an increase in PKC activity. These results show the impact that Minerval has on membrane structure and protein function and might shed light on the knowledge of the antitumoral properties of this molecule. doi:10.1016/j.chemphyslip.2007.06.075

Transcript of The role of lipid microviscosity changes in inactivation of the opioid receptors of brain synaptic...

Page 1: The role of lipid microviscosity changes in inactivation of the opioid receptors of brain synaptic membranes

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shed light on the knowledge of the antitumoral properties

Abstracts / Chemistry and Ph

O 26he role of lipid microviscosity changes in

nactivation of the opioid receptors of brainynaptic membranes

lena Maltseva, Olga Belokoneva

Institute of Biochemical Physics of Russian Academy ofciences, Russia

he fluidity of membrane lipids takes part in regulationf the membrane-bound receptors. The binding activityf the opioid receptors detected by antagonist-naloxones stabilized by unsaturated fatty acids, acidic phospho-ipids and ionol (4-methyl-2,6-ditretbutylphenol). Tonderstand the mechanism of spontaneous inactivationf membrane-bound opioid receptors it was studiedhe changes of lipid microviscosity during incubationf rat brain synaptosomes (at 37 ◦C) in the presencef various effectors such as the unsaturated fatty acidsarachidonic, palmitic and linoleic) and syntheticntioxidants—ionol and phenozan K (potassium salt of-hydroxy-3,5-ditret-butyl-phenylpropoinic acid).Theipid microviscosity was studied by EPR-techniquen the computerized spectrometer Bruker-200D usingwo spin-probes: 2,2,6,6-tetra-methyl-4-capryloyl-xipiperidine-1-oxyl(1) and 5,6-benzo-2,2,4,4-tetra-ethyl-1,2,3,4-tetra-hydro-gamma-carbolin-3-oxyl(2),

referentially localized in the surface and annularembrane lipids correspondingly. The value of micro-

iscosity was estimated by rotational correlation timeTc) of spin probes using formula for fast-rotated radi-als. It was shown that these unsaturated acids increasedc − 2 during incubation time (1 h), the effect of linoleiccid is more (20%)than others; ionol and, especially,henozan K decreased Tc − 2. All effectors (but nothenozan K) increased Tc − 1 compared with controllinoleic acid—in more extent as well); but the valuesf Tc − 1 decline exponentially during incubation in allases. It was obtained the correlation between changesf Tc − 1 and rates of receptors inactivation, which cane described by an empirical equation. It was proposed

hat destabilization of the opioid receptors caused byncreasing lipid fluidity of synaptic membranes.

oi:10.1016/j.chemphyslip.2007.06.074

Lipids 149S (2007) S23–S49 S33

PO 27Effects of Minerval on fatty acid andphospholipid composition in mice tissues andhuman glioma cells

Maria Laura Martin, Gwendolyn Barcelo-Coblijn,Maria Antonia Noguera, Silvia Teres, Pablo V. Escriba

Laboratory of Molecular Cell Biomedicine,Department of Biology, Institut Universitarid’Investigacio en Ciencies de la Salut (IUNICS),University of the Balearic Islands, Spain

Minerval (2-hydroxy oleic acid) is a potent antitumordrug, whose actions are related to its effects on themembrane lipid structure and the function of importantmembrane proteins. Changes in membrane lipid com-position alter membrane structure, protein–membraneinteractions and cell signaling. In order to investigatewhether Minerval treatments modify membrane lipidcomposition, we determined changes in phospholipidmass, phospholipid fatty acid composition, and choles-terol mass in livers, hearts and brains of mice treatedwith 600 mg/(kg day) of Minerval for 10 days. We alsoanalyzed membrane lipids in human glioma cell lines(U118 and SF-767) treated with Minerval. Animals andcells treated were compared with the correspondinguntreated controls. We observed that brain phospholipidcomposition was not significantly altered by Minervaltreatment while brain cholesterol content decreased intreated mice. On the other hand, Minerval treatmentsinduced increases in the levels of monounsaturated fattyacids, mainly C18:1. To understand the effect of Min-erval on protein function, we analyzed its effect on thelocalization of signaling peripheral proteins. For this pur-pose, SF-767 cells were treated with Minerval (200 �M)for 1 and 24 h. Minerval induced reductions of PKC con-tent in the soluble fraction and increase in the membranefraction, which is associated with an increase in PKCactivity. These results show the impact that Minerval hason membrane structure and protein function and might

of this molecule.

doi:10.1016/j.chemphyslip.2007.06.075