Stabilization of synaptic membranes by alpha-tocopherol against the damaging action of phospholipases. Possible mechanism of biological action of vitamin E.

Using fluorescent and ESR-spin probes, the effects of phospholipases A2, C and D on rat brain synaptosomal membranes were investigated. It was shown that the exposure of synaptosomal membranes to phospholipases A2, C and D results in their depolarization and an increase of the negative surface potential. In the case of phospholipases A2 and C, these changes are associated with a decrease of the microviscosity of the membrane lipid bilayer. alpha-Tocopherol stabilizes synaptosomal membranes against the damaging action of the phospholipases. This stabilization consists in the reconstitution of the transmembrane potential and an increase of microviscosity of the phospholipase-treated membranes. The stabilizing effect of alpha-tocopherol is due to the binding of phospholipid hydrolysis products, but not to the inhibition of phospholipases. The observed stabilization of synaptosomal membranes by alpha-tocopherol is regarded as a possible mechanism of biological action of vitamin E on biomembranes.

[The ATP content of the neutrophils and whole blood in the inhabitants of regions in the Altai Territory subjected to nuclear testing exposure]. / Soderzhanie ATF v neitrofilakh i tsel'noi krovi u zhitelei raionov Altaiskogo kraia, podvergshikhsia vozdeistviiu iadernykh ispytanii.

The bioluminescent method was used in the studies of the influence of ionizing irradiation and/or xenobiotics on the content of ATP in RBC and neutrophils of rats, and in whole blood and neutrophils of 80 examined women of Altai Region exposed to ionizing radiation during a series of nuclear tests in Semipalatinsk in 1949-1965. Deviations from the normal ATP content were measured with due to account of the natural variability of a given metabolite. For rats, deviations from the content of ATP in erythrocytes were short-term, those in neutrophils were long-term. For people, a statistically significant increase in the content of ATP in neutrophils as compared to the control was observed. A non-linear correlation between the content of ATP in neutrophils and the calculated dose of radiation was observed. An increase in the ATP content in whole blood, with regard to the control, was not statistically significant for all groups of examined persons.

[Comparative study of the effect of inhibitors of monoamine oxidase and ftorafur on the growth of de-differentiated astrocytoma]. / Sravnitel'noe izuchenie deistviia ingibitorov monoaminoksidazy i ftorafura na rost dedifferentsirovannoi astrotsitomy

To evaluate the possible antitumour effect of intensified deposition of serotonin in the region of localization of the tumour caused by a pharmacological preparation studies of the effect of inhibitors of monoamine oxidase transamine and N2N2-dibenzylhydrazide of DL-malic acid on rat's cerebellum tumour de-differentiated by astrocytoma (strain No 101/12) were carried out. The effect of inhibitors of monoamine oxidase was compared with that of antiblastic preparation of phthorafur. Differences in the mechanisms of action of pharmacological agents referred to above are shown. It was established that inhibitors of monoamine oxidase administered against the background of the developing tumour caused a considerable reduction in its weight and prononced dystrophic and necrotic changes.

[The indices of free-radical oxidation in the umbilical cord blood and placenta of inhabitants of the Altai Territory]. / Pokazateli svobodnoradikal'nogo okisleniia v plazme pupovinnoi krovi i platsente zhitel'nits Altaiskogo kraia.

Free-radical processes were studied in the umbilical blood and placenta of women from the regions of the Altai Territory, which were affected to different extents by nuclear tests on the Semipalatinsk grounds in 1949-1965. The data was obtained, which suggest changes of free-radical processes, from studied materials from women in labor in the regions most affected by the consequences of tests. The activity of erythrocytic superoxide dismutase was decreased, thus suggesting the formation of structural-functional defects of the erythrocytes. The data corresponds to the results obtained earlier when studying free-radical processes in the venous blood samples from female residents of the Altai Territory.

[Parameters of free radical oxidation in blood plasma of women from the Altai region]. / Pokazateli svobodnoradikal'nogo okisleniia v plazme krovi zhitel'nits Altaiskogo kraia.

We studied the indices of free radical-mediated processes in blood plasma of women from the Altai district affected by the nuclear weapon tests at the Semipalatinsk ground in 1949-1962 and 1965. The data obtained suggest modifications of free radical-mediated processes in inhabitants of the regions most affected by the tests. A significant decrease in the activity of erythrocytic superoxide dismutase indicates structural and functional disturbances of the erythrocytes.

[Effect of hydrocortisone on alpha-glycerophosphate dehydrogenase activity in KOX-1 and mouse glioblastoma EPNT-5 cells]. / Vliianie gidrokortizona na aktivnost' alpha-glitserofosfatdegidrogenazy v kletkakh KOX-1 i glioblastomy myshi EPNT-5.

A comparative cytochemical investigation for alpha-glycerophosphate dehydrogenase (alpha-GPhD) activity in transplanted cellular line of mouse glioblastoma (EPNT-5) and KOX-1 was performed under normal conditions and under hydrocortisone effect. In glioblastoma EPNT-5 cells a high alpha-GPhD activity was revealed. The enzymatic activity was found to correspond to the dynamics of cell multiplication. Under the effect of hydrocortisone, alpha-GPhD activity demonstrated a two-fold increase, while alpha-GPhD activity in KOX-1 cells was very low, and hydrocortisone did not induce its increase. The data obtained supported the view on the glial nature of the transplanted cpHT-5 line and demonstrated that the glial elements preserved their specific peculiarities at a prolonged cultivation.

[Alpha-tocopherol protects beta-adrenoreceptors of the rat brain from damaging effects of phospholipase A2]. / alfa-tokoferol zashchishchaet beta-adrenoretseptory mozga krys ot povrezhdaiushchego deistviia fosfolipazy A2.

The effect of synaptosomal membrane phospholipid hydrolysis by phospholipase A2 and alpha-tocopherol upon the state of beta-adrenergic receptors has been studied. The damaging action of phospholipase A2 on beta-adrenergic receptors, consisting in the decrease of specific binding of 3H-dihydroalprenolol at the expense of diminishing receptor affinity and Bmax was demonstrated. It was shown, that alpha-tocopherol protects beta-adrenergic receptors from damaging effect of phospholipase A2.

[Change in cerebral beta-adrenoreceptors in experimental neurosis]. / Izmenenie sostoianiia beta-adrenoretseptorov golovnogo mozga pri éksperimental'nom nevroze.

Pathological and adaptive-compensatory alterations of rat cerebral cortical beta-adrenergic receptors have been demonstrated using the model of experimental neurosis developing as a result of chronic emotional painful stress. After the first week of stress increases of both Kd and Bmax occur; both indexes reach control levels after 3 weeks of neurotization. The changes of cortical beta-adrenoreceptors accompany transient fall of cholesterol-to-phospholipid ratio and decrease of free radical lipid oxidation in brain cortex. The normalization of all cerebral parameters after 3 weeks of stress coincides with the activation of lipid peroxidation in blood serum.

[Effects of alpha tocopherol and free fatty acids on physical properties of lipid matrix and adenylate cyclase activity in rat brain synaptosomes]. / Deistvie alfa-tokoferola i svobodnykh zhirnykh kislot na fizicheskie svoistva lipidnogo matriksa i aktivnost' adenilattsiklazy sinaptosomommozga krys.

Using modification of physical state of synaptosome lipid matrix by free fatty acids and alpha-tocopherol it was shown that fluidity of lipid matrix isn't limiting regulating factor for the activity of alpha-adrenergic aden late cyclase. From the point of view that state of annular lipids is different from the state of lipid bilayer in synaptosomes we suggest that composition of annular lipids regulates alpha-adrenergic adenylate cyclase system in rat neuronal membranes.

[Transport of ions into human erythrocytes in various forms of hemolytic anemia: a correlation analysis]. / Transport ionov v éritrotsitakh cheloveka pri razlichnykh formakh gemoliticheskoi anemii: korreliatsionnyi analiz.

The activity of Na+, K(+)-ATPase (ouabain-inhibited 86Rb influx), Na+, K+ cotransport (ouabain-insensitive furosemide-inhibited 86Rb or 22Na influx), Na+/Na+ exchange (ouabain-insensitive phloretin-inhibited 22Na influx) and Na+/Li+ exchange (ouabain-insensitive Na0(+)-depended Li+ efflux) as well as the passive permeability of the erythrocyte membrane for Na+, K+ and Li+ have been studied in patients with primary (microspherocytosis, hemoglobinopathy) and secondary (autoimmune) hemolytic anemia. The activities of the Na+, K(+)-pump and Na+, K(+)-cotransport were increased in patients with microspherocytosis-by 45% and 70%, respectively. In patients with hemoglobinopathy the Na+/Li+ exchange and passive permeability for K+ were increased 2-3-fold in comparison with the control with the control group. The increased passive permeability for K+ may partly be due to the increased K+, Cl(-)-cotransport. In patients with autoimmune anemia the 3-fold increase in the passive permeability for monovalent cations and the 2-fold increased activity of Na+, K+ cotransport were found. There was no significant correlation between the Na+/Na+ and Na+/Li+ exchange which suggests that the cellular mechanisms of activity control in those ion transport systems differ essentially. No correlation was found between the passive permeability for Na+ and K+ either. These data indicate that simple diffusion (leakage) is not the only pathway for the passive permeability of the erythrocyte membrane for monovalent cations.

[Increase in the damaging effect of free fatty acids on brain synaptosomes induced by vitamin E deficiency]. / Usilenie povrezhdaiushchego deistviia svobodnykh zhirnykh kislot na sinaptosomy mozga pri defitsite vitamina E.

Using fluorescent probes it has been shown that free fatty acids cause depolarization of synaptosomes isolated from the rat brain. At the same time free fatty acids stimulated 45Ca2+ transport into synaptosomes. It has been demonstrated that synaptosomes isolated from the brain of E-deficient rats were more sensitive to the action of free fatty acids. Depolarization of synaptosomes isolated from the brain of both control and E-deficient rats were reduced by the addition of exogenous alpha-tocopherol.

[Activation of calcium transport in synaptosomes by phosphatidylinositol-specific phospholipase C]. / Aktivatsiia transporta kal'tsiia v sinaptosomakh fosfolipazoi C, spetsifichnoi k fosfatidilinozitam.

The isotope labeling method was used to study the influence of phospholipases C of different origin and specificity on Ca2+ accumulation in rat brain synaptosomes. It was found that phospholipases C specific to phosphatidylinositides (PI) stimulate Ca2+ transport into synaptosomes, while non-specific phospholipase C, which hydrolyzes different membrane lipid fractions, decreases the Ca2+ content in synaptosomes. It is supposed that the stimulating effect of PI-specific phospholipases C is determined by the activation of PI metabolism, which results in an increase in the content of some PI metabolism products serving as Ca2+ ionophores in synaptosomal membranes. The inhibition of Ca2+ uptake by synaptosomes treated with non-specific phospholipase C is thought to result from partial disruption of synaptosomal membranes.

[Protection of beta-adrenoreceptors of the rat brain during emotional-pain stress by oxidants of the steric hindrance class of phenols]. / Zashchita beta-adrenoretseptorov mozga krys pri émotsional'no-bolevom stresse antioksidantom klassa prostranstvenno-zatrudnennykh fenolov.

Adaptogenic properties of a new antioxidant-isoquinoline derivative of hindered phenol class under pain-emotional stress have been investigated. This new antioxidant was shown to have stress-protective effects, i.e. it stabilizes cerebral beta-adrenoreceptors, inhibits lipid peroxidation and stimulates anti-radical defense systems in the brain and serum, as well as normalizes vegetative functions in rats.

[Changes in the physico-chemical properties of synaptosomal membranes induced by phospholipase A2]. / Izmenenie fiziko-khimicheskikh parametrov membran sinaptosom pod deistviem fosfolipazy A2.

Using fluorescent and EPR spin probing techniques, the changes in the physico-chemical properties of rat brain synaptosomal membranes induced by phospholipase A2 were studied. It was shown that treatment of synaptosomal membranes with phospholipase A2 leads to their depolarization, increases their surface negative potential and decreases the microviscosity of the membrane lipid bilayer. The observed changes in the physicochemical properties of synaptosomal membranes induced by phospholipase A2 are discussed in terms of a possible regulatory role of lipids in the transmembrane chemical signal transfer.

[The role of lipids in the changes in the properties of the brain beta-adrenoreceptors during emotional stress]. / Rol' lipidov v izmenenii svoistv beta-adrenoretseptorov mozga pri émotsional'no-bolevom stresse.

The role of phospholipid hydrolysis by phospholipase A2 and lipid peroxidation in changes of the properties of beta-adrenoreceptors in rat brain synaptosomes in severe emotional painful stress (EPS) has been evaluated. It has been shown that EPS does not influence lipid and fatty acid content of synaptosomal membranes but significantly increases the amount of lipid peroxidation products. Activation of lipid peroxidation in EPS causes a decrease in specific binding of 3H-dihydroalprenolol. The free radical scavenger, 4-methyl-2,6-di(tret-butyl)phenol completely prevents activation of lipid peroxidation and eliminates the disturbances in ligand-receptor interactions in EPS.