Zeta potential response of human erythrocyte membranes to the modulators of Gardos channel activity under low rate ß-radiation. / Reaktsiia dzeta potentsiala membran éritrotsitov cheloveka na moduliatory aktivnosti Gardos kanalov na fone ß-izlucheniia maloi moshchnosti.

OBJECTIVE: Study of human erythrocyte DP response under modification by activators and blockers of the functional state of Ca2+-dependent K+ channels under low rate ß-radiation. MATERIALS AND METHODS: Erythrocytes were isolated from the donor blood. The zeta potential was computed from the value of the cell electrophoretic mobility. The investigated drugs preliminary introduced in cellular suspensions, and then aliquote of 90Sr(NO3)2 solution to get the final activity concentration of 44,4kBq⋅l-1. RESULTS: The radioisotope radiation of 90Sr/90Y (RR, 15 µGy⋅h-1) increases an absolute value of erythrocyte membranes DP (DPab), and its action is reversible. It specifies the effect is mediated by non-ionizing part of the RR. Dibutyril-cAMP dose-independent increases DPab of erythrocyte membranes in the concentration range of 1-100 мкМ, but RR does not amplify this effect. Anaprilin increases dose-independent DPab in concentrations 10 and 100 µÐœ. The effect of maximal concentration of anaprilin (100 µÐœ) decreases by RR. Clotrimazol increases DPab of erythrocyte membranes in the concentration range of 0,1-10 µÐœ relatively control, while its maximal concentration - decreases, and the minimal level does not reliably influence on this index The action of сlotrimazol on DP in concentrations of 10-100 µÐœ is abolished by RR, and is not changed in the range of 0,1-1,0 µÐœ. Nitrendipine raises DPab of erythrocyte membranes in all of range of concentrations, and RR amplifies the effect of the drug. CONCLUSIONS: 1. There is a threshold of the biological action on cells for the ionizing component of radioisotope radiation determined by efficiency of operation their antioxidant system.2. At dose rates below a threshold, the action of ionizing radiation is mediated by its non-ionizing component, and is reversible, and therefore is determined only in the field of radiation.

[Biochemical mechanisms of fluorine action]. / Biokhimicheskie mekhanizmy deistviia ftora.

Biochemical mechanisms of fluorine ion action accounting for the biological role and significance of fluorine for vital activity of the organism are investigated. Results of these investigations are generalized. This trace element is shown to participate at least in two vitally important systems of the organism: the adenylate cyclase system which accounts for the cell response to neuroendocrinological information and the immune protection system providing antimicrobic resistance. Available data permit considering that cytotoxic fluorine action is based on the ability to hinder protein synthesis in eukaryotes and to stimulate peroxidation processes of biomembrane lipids. Inorganic fluorine compounds are recommended to be used with the treatment-and-prophylactic purpose for certain pathologic states, associated with its insufficient or excessive arrival into the organism.

[Morpho-functional state of biomembranes after treatment with alkyl derivatives of 2,4-dinitrophenol]. / Morfofunktsional'noe sostoianie biomembran pri vozdeistvii alkilproizvodnykh 2,4-dinitrofenola.

The morphofunctional state of the rat liver biomembranes is studied under conditions of the peroral effect of alkyl dinitrophenols: dinitroorthocresole and secondary 2,4-dinitro-6-butylphenol. It is established that free radicals and products of peroxide lipid oxidation (diene conjugates, hydroperoxides, final products reacting with 2-thiobarbituric acid) are very important for realization of the membrane-tropic action of the above compounds. Possible mechanisms of development of the membrane-damaging action of these xenobiotics and their effect on the state of the mitochondrial respiratory chain are discussed. The membrane-tropic effect of alkyl dinitrophenols is confirmed by the results of electron-microscopic studies.

[Structural rearrangement in leukocyte membranes under the effect of quercetin and linoleic acid hydroxamate]. / [Strukturnye perestroiki v membranakh leikotsitov pri deistvii kvertsetina i gidroksamata linolevoi kisloty.

The character of structural rearrangements in leukocyte membranes affected by 5-lipoxygenase inhibitors: quercetin and linoleic acid hydroxamate, has been investigated. Quercetin has been shown to induce the translocation of tryptophanyls and tyrosyls from membrane protein inner regions to their surface. Linoleic acid hydroxamate produces the analogous transition of tyrosine residues only. Quercetin brings out disturbances of surface membrane proteins as was registered by ANS fluorescent parameters. It is likely able to arise from the increase of protein hydration. The linoleic acid hydroxamate elevates the quantity of ANS binding sites on the membrane surfaces without any change in their structural features. This effect is likely induced by the surface charge modification of the leukocyte membranes. The linoleic acid hydroxamate increases the level of protein descent into the lipid matrix and decreases the polarity and microviscosity of hydrophobic regions of the latter.

[Structural changes in membranes of proliferating leukocytes L-41 as affected by low doses of ionizing radiation]. / Strukturnye izmeneniia v membranakh proliferiruiushchikh leikotsitov L-41 pod deistviem nizkikh doz ioniziruiushchego izlucheniia.

The dose-dependent effects of gamma-radiation on the leucocyte cultures L-41 has been investigated. Irradiation by the dose of 0.25 Gy stimulates the cell proliferation while that by the doses of 1.0 and 2.0 Gy inhibits this process. In this dose range the radiohormesis effects characterizing structural organization of the probed membranes have been also registered for fluorescence parameters. The zone of qualitative transition of response of the cell membranes to radiation is individual for various effects. The action of radiation in the doses of 0.25 and 0.50 Gy induces a decrease of ANS fluorescence intensity and a decrease of membrane protein immersion in the lipid bilayer of leukocyte membranes. The values of these parameters rise at the doses of 1.0 and 2.0 Gy that reflects different directions of structural changes in various membrane regions. The irradiation in the range of 0.25-1.0 Gy induces the increase of microviscosity in deep regions of membrane lipid matrix while at the dose 2.0 Gy it causes its decrease. Radioactive radiation does not change the membrane protein conformation of leukocytes and polarity of lipid bilayer hydrophobic zones as recorded by fluorescent methods used.

[Effect of 1,8-ANS on structural characteristics of cardiomyocytes sarcolemma]. / Vliianie sufana na strukturnye svoistva plazmaticheskoi membrany kardiomiotsitov.

The effect of sufan on structure properties of the rat cardiomyocyte sarcolemma was investigated. Fluorescence methods involving the probing with 1-anilino-8-naphthalene-sulfonate or pyrene and the self-fluorescence of membrane proteins was used. Effect of sufan on the cardiomyocyte sarcolemma structure has been determined to provoke the conformational disturbances. These are the compaction of membrane proteins and translocation of their tryptophanyls from the surface to the interior of macromolecules. This process was accompanied by the increase of a protein plunge into the lipid matrix. Sufan induces a decrease of the microviscosity without a change of the polarity index in hydrophobic region of the lipid bilayer. These mechanisms have been supposed to be significant for the exhibition of sufan cardioactive properties.

[Structural effects in membranes after exposure to methyl (embiquin) and metaxylyl derivatives of chloroalkylamines]. / Strukturnye éffekty v membranakh pri vozdeistvii metil'nogo (émbikhin) i metaksil'nogo proizvodnykh khloralkilaminov.

Chloroaklylamine derivatives are studied for their effect on the structural organization of mitochondrion and microsome membranes of the cattle liver. The antitumoural preparation--embiquin is shown to increase microviscosity of hydrophobic zones of a lipid matrix of mitochondrial membranes and to decrease the quantity of immobilized cytochrome C, whereas it has no effect on microsomal membranes. It is established that the replacement of a methyl substituent in the nitrogen atom of chloroalkylamines by the metaxylyl one evokes no qualitative differences in the character of disturbances of the structural properties of mitochondrial membranes, however it induces structural perturbations in the microsomal membranes.

Character of structural disturbances caused by chloroalkylamines in the model and erythrocyte membranes.

beta, beta-Dichlorodiethylamine is proved not to induce structural disturbances in phosphatidylcholine liposomes and erythrocyte membranes which is registered by fluorescence methods. Methyl-beta, beta-dichlorodiethylamine and metaxylyl-beta, beta-dichlorodiethylamine cause the increase in microviscosity of lipid bilayer hydrophobic areas in both erythrocyte membranes and liposomes. Besides, polarity of the latter also decreases, and the metaxylyl derivative alkylates nucleophilic centers of phospholipid phosphate groups in liposomes. Erythrocyte membranes, being treated by beta, beta-dichlorodiethylamine derivatives, the increase in the membrane protein hydrophobicity is registered as well as the decrease in their immersion in the lipid bilayer.

[Structural effects in the sarcolemma of the cardiomyocytes under the action of modulators of the polyphosphoinositide system]. / Strukturnye éffekty v sarkolemme kardiomiotsitov pri deistvii moduliatorov polifosfoinozitidnoi sistemy.

The influence of activators (Ca(2+)-channels stimulator BAY K 8644 and phospholipase C stimulator fMLP) and inhibitors (Ca(2+)-channels blocker verapamil and alpha 1-adrenoceptors blocker prazosin) of the polyphosphoinositide system on cardiomyocytes sarcolemma, was studied. The structural effects of the PPI modifiers seem to be one of the mechanisms of the PPI physiological activity at the membrane level.

[Effect of the fatty component of the food ration on the ionic permeability of bilaminar phosphatidylcholine membranes]. / Vliianie zhirovogo komponenta pishchevogo ratsiona na ionnuiu pronitsaemost' bisloinykh fosfatidilkholinovykh membran.

Five molecular types of phosphatidyl-cholines, viz. that of the chicken egg and of four others, isolated from the liver of rats fed on rations with qualitatively different fats, were used in forming double-layer membranes. A gas-chromatographic analysis established distinctive differences in the fatty acids composition of phosphatidylcholines obtained from the rat liver. The degree of their oxidation was controlled by determining the level of dienic conjugates. No relationship between the permeability for inorganic ions and the composition of the phosphatidyl-cholines fatty acids could be established. It appears that in phosphatidyl-choline membranes at the basis of ionic permeability there lies some other mechanism than in the case of uncharged low-molecular substances.

[Effect of retinol and alpha-tocopherol on the stability of phosphatidylcholine bilayer membranes]. / Vliianie retinola i alpha-tokoferola na stabil'nost' fisloinykh fosfatidilkholinovykh membran.

The modifying action of retinol and alpha-tocopherol on the stability of bilayer phosphatidyl choline membranes was studied under control of their oxidation. The membranous stability was determined by the time during which the value of the ionic conduction of the membrane in a stationary condition remained unchanged. It was shown that the stability of the membranes modified by the addition of retinol and alpha-tocopherol was not a monotonous function of the modifier concentration in the membrane (but it was achieved through maximum). The ionic conduction of bilayer membranes modified by vitamines was constant with all the tested concentrations at which the bilayers were formed while high concentrations of cholesterol decreased appreciably the ionic conduction.

[Effect of the total replacement of fats in the diet with a phospholipid concentrate on oxidative phosphorylation in liver mitochondria and the lipid composition of the plasma and liver in rats]. / Vliianie polnoi zameny zhirov v ratsione fosfolipidnym kontsentratom na okislitel'noe fosforilirovanie v mitokhondriiakh pecheni i lipidnyi sostav plazmy i pecheni u krys.

Experimental rats were given rations with 100% substitution of fats for phospholipid concentrate, during 1 and 3 months. It was found that such rations produced hypolipidemic and hypocholesterolemic effects, that were most pronounced at the end of the experiment. A control ration with sunflower oil containing high levels of unsaturated fatty acids induced accumulation of lipid peroxides in the hepatic tissue and blood plasma of the animals fed with the ration during 3 months. The ration containing the phospholipid concentrate did not produce such an effect. The data obtained have evidenced a positive influence of the phospholipid concentrate on the lipid metabolism parameters studied.

[Biological value of the meat from animals implanted with betazine and diiodotyrosine and its effect on the body]. / Biologicheskaia tsennost' miasa zhivotnykh, implantirovannykh betazinom i diiodtirozinom, i ego vliianie na organizm.

The biological value of beef and pork of the animals implanted with antithyroid preparations did not differ from that of controls in varying tests. A long-term feeding of rats with diets containing meat of young bulls and pigs, implanted with betazine and diiodotyrosine, did not influence the content of free and bound cholesterol and total phospholipids in the liver, and produced no effect on the intensity of oxidative phosphorylation in the mitochondria which was proved by the results of the morphological, histochemical and ultrastructural investigations.

[Participation of proteinkinase CK2 in regulation of human erythrocytes plasma membrane redox system activity: relative contribution of ca(2+)-dependent and ca(2+)-independent mechanisms of its activation].

Involvement of protein kinase CK2 (2.7.11.1) in modulation of live cells trans-plasma membrane electron transport was first discovered. Using human erythrocytes a decrease of plasma membrane redox system (PMRS) activity is shown under the action of specific protein kinase CK2 inhibitors. Using inhibitory analysis the activity regulation of human erythrocytes PMRS by Ca(2+)-dependent and Ca(2+)-independent mechanisms were investigated. It was shown that functional Ca(2+)-antagonists (nitrendipine and calmidazolium) significantly increased, and functional Ca(2+)-agonists to some extent reduced or did not affect the trans-plasma membrane electron transport in these cells.

[An enzyme-mediated mechanism of sodium nitroprusside NO-donating activity in the rat aorta].

The mechanisms of NO-mediated physiological activity of sodium nitroprusside (SNP) have been investigated in isolated rat aorta segments. It was shown, that in pretreated with 1.5 mM NaCN aorta segments SNP causes slight vasoconstriction. Heme-oxidizer K3Fe(CN)6 markedly suppressed SNP-induced vasodilatation. Also it was revealed that NaCN inhibits NO2- accumulation, which was observed in buffer solution with SNP after addition of microsomal membranes isolated from rat aorta homogenates. The great importance of cell membranes heme-containing enzymes for display of SNP NO-donating activity and the possibility of SNP-released CN- involvement in suppression of SNP-induced vasodilatation is discussed.

[Sodium azide as indirect nitric oxide donor: researches on the rat aorta isolated segments].

A comparative investigations of heme-containing enzymes inhibitors NaN3 and NaCN effects on the rat aorta isolated segments tone has shown that NaN3 in the range of very low concentrations from 10(-9) to 10(-6) M displays pharmacological activity characteristic of nitric oxide (NO) donors, which is inhibited by NaCN. The value of vasodilatation, caused by NaN3, was also decreased in the presence of soluble guanylate cyclase inhibitor ODQ (10(-5) M). It was found that H2O2 injection to physiological solution containing NaN3 and horseradish peroxidase or catalase lead to NO2- accumulation in it, which was blocked by NaCN. The nonenzymic NaN3 oxidization by hydrogen peroxide was not found in control experiments. NaN3 physiological activity dependent on NO-donating properties of this traditional inhibitor of heme-containing enzymes is discussed.

[Influence of beta-radiation on human erythrocyte surface potential under eicosanoid metabolism inhibition]. / Vliianie beta-izlucheniia na poverkhnostnyi potentsial éritrotsitov cheloveka pri ingibirovanii metabolizma éikozanoidov.

The aim of the research consisted in the study of influence of beta-radiation on response of erythrocyte surface potential to inhibitors of eicosanoid metabolism enzymes (cyclo-, lipoxygenase and phospholipase A2). It was shown, that inhibitors of phospholipase A2 (quinacrine, 10-100 microM), cyclooxygenase (aspirin, 10-100 microM) and cyclo- and lipoxygenase (BW755c, 1-100 microM) lowered electrophoretic mobility (EPM) of erythrocytes by 20-30%. An analogous effect can be exerted by beta-radiation. Nonradioactive leucine in the studied concentrations cannot simulate EPM erythrocytes. Response of cellular EPM to these inhibitors depended on their concentration in the incubation medium. Addition of 14C to the incubation medium changed response of EPM of cells to inhibitors of cyclo- and lipoxygenase but not to quinacrine. However beta-radiation fully abolished the stimulative action of nonspecific activator of phospholipase A2 (Ca-independent), H2O2, on cellular EPM. Under these conditions beta-radiation enhanced EPM response to aspirin only at concentration of 100 microM. The EPM response to BW755c is reduced by irradiation at all concentrations with the exception of equal-effective one (10 microM). Data obtained evidence for modification of eicosanoid metabolism by beta-radiation, probably, as a result of phospholipase A2 inhibition, as evident from elimination by radiation of stimulated action of hydrogen peroxide on EPM. The radiation action can also affect the cyclooxygenase lipoxygenase activity ratio, this activity being mediated by cellular membrane signaling systems.

[Effect of ultra-low dose of ionizing radiation on the surface potential of erythrocytes]. / Vliianie ioniziruiushchego izlucheniia v sverkhmaloi doze na poverkhnostnyi potentsial éritrotsitov.

Effect of ionizing radiation in ultralow dose (5 microGy) on responses of erythrocyte electrophoretic motility (EPM) as a result of adrenoreceptor ligands binding (0.01-100 microM) has been investigated. The opposite directional EPM responses to agonists (adrenaline, isoprenaline) and antagonist (propranolol) of beta-adrenoreceptors was shown. At that, EPM response to the radiation coincides both with the direction and value of acting the beta-adrenoreceptor agonists depressing EPM. The EPM response to a combined action of beta-adrenoreceptors antagonist, propranolol (10 microM), and ionizing radiation is additive. The above listed is capable to evidence about the essential role of adrenoreceptors at formation of erythrocyte membrane surface charge under action of ionizing radiation in ultralow doses.