[Transamination in the mechanism of protection of mitochondria from Ca2+ overload].

A high sensitivity of the succinate-dependent uptake of Ca2+ by mitochondria to (1) the transamination (TA) substrates glutamate (GLU) and alpha-ketoglutarate (KGL) and (2) the inhibitor of TA aminooxyacetate (AOA) was revealed. The effect of the TA substrates on Ca2+ uptake depends on the ratio (1:10 mM) of their concentrations: 1 mM GLU activates and 10 mM KGL decreases this activation by 35-46%, whereas AOA suppresses the Ca2+ capacity by 60% and the inhibitor of succinate oxidation malonate, by 80-90%. A similarity in the limiting action of KGL and phosphoenolpyruvate (PEP), two sources of oxaloacetate (OAA) and GTP, on Ca2+ capacity was revealed. The differences in the effects of KGL and GLU and the similarity in the effects of KGL and PEP on succinate oxidation are explained by the effect of OAA and GTP on this oxidation. The alternating inflow of OAA in coupled processes of TA, pyruvate cycle, and tricarboxylic acids cycle provides the reciprocal activation and cyclic recurrence of Ca2+ uptake, i. e., protection from the chronic exhausting activation of Ca2+-regulated dehydrogenases, the overload of Ca2+-outgoing channels, and the excessive production of free radicals in mitochondria. The reciprocal regulation of Ca2+ uptake by TA is considered as a mechanism of the maintenance of Ca2+ homeostasis and protection of mitochondria against Ca2+ overload.

[Correlation between succinate-dependent Ca2+ accumulation and transamination in the heart and the liver mitochondria of experimental animals].

Glutamate (GLU) and alpha-ketoglutarate (KGL), the substrates involved in transamination, have reciprocal effects on succinate-dependent respiration, NADH reduction, as well as on the accumulation and stable retention of Ca2+ in heart and liver mitochondria and homogenates from experimental animals. The succinate-dependent Ca2+ accumulation was shown to be highly sensitive to changes of the concentration ratios of GLU and KGL within the range 1:10 mM. GLU activated this process by transamination of oxalacetate (OAA) to aspartate. The predomination of KGL blocked the activating effect of GLU. The predomination of GLU eliminated the block produced by KGL or phosphoenolpyruvate (sources of OAA and GTP) but did not eliminate the Ca2+ accumulation-suppressing effect of aminoacetate, inhibitor of transaminases.

[Assessment of energy-dependent Ca2+ transport in myocardial mitochondria in the ventricular fibrillation: potential diagnostic implication]. / Otsenka énergozavisimogo transporta Ca+ v mitokhondriiakh serdechnoi myshtsy pri fibrilliatsii zheludochkov: diagnosticheskie vozmozhnosti metoda.

The method of evaluation of ATP synthesis from ADP and Ca2+ transport in myocardial mitochondria has been developed. The addition of glutamate to the homogenisation media improved the parameters studied. It was shown that the Ca2+ transport test is highly informative and sensitive for the estimation of heart muscle energetic state.

[Liver mitochondria in antigenic stress in rats]. / Mitokhondrii pecheni v realizatsii antigennogo napriazheniia organizma u krys.

The penomenon of reciprocal regulation of succinate dehidrogenase activity in rat liver mitochondria was elicited in antigenic strain induced by the administration of activated lymphocytes from animals with allotransplated heart. Two coupled but opposite changes (simultaneous activation and inhibition) in succinate depended ATP synthesis and calcium transport occur. The inhibition was correlated with the activation of synthetic processes in hepatocytes. Similar changes were provoked by epinephrine (either administered i.p. or released endogenously under immobilization stress and in myocardium infarction) as well as in patients with stomach tumor. The physiological significance of the reciprocal regulation of succinate dehydrogenase is discussed.

[Physiologic activation of peroxidation by negative air ions]. / Fiziologicheskaia aktivatsiia perekisnogo okisleniia otritsatel'nymi aéroionami.

The effect of negative air ions (NAI) was investigated on physiological processes of peroxidative oxidation in mitochondria preserving their native structure organization in associations in rat liver homogenate. Tchijevsky lustre generating superoxide was served as a source of NAI. The investigated objects were put into solutions pretreated with NAI flow. An increase of peroxide induced Ca2+ release from mitochondria loaded with the cation was found. Under prolonged action of NAI flow on homogenates kept in ice followed by incubation in media pretreated with NAI an elevation of products of peroxide lipid oxidation (POL) was found in case of their low initial level and decrease of POL products in case of their high initial level. The range of changes is considerably less than under pathogeneous rise of POL. The discovered mild activation of peroxidative oxidation within physiological range of POL concentrations is considered as a primary physico-chemical mechanism of beneficial biological action of NAI.

[Dual reciprocal regulation of the succinate oxidation system in heart and liver mitochondria in pathological conditions]. / Dvoinaia retsiproknaia reguliatsiia sistemy okisleniia suktsinata v mitokhondriiakh serdtsa i pecheni v usloviiakh patologii.

The phenomenon of the dual reciprocal regulation of succinate dependent 2H+/Ca2+ exchange was studied in heart and liver mitochondria of experimental animals (allogenic heart transplantation in rat; myocardium infarction in rabbits; pulmonary arteria coarctation in dogs) and in liver bioptates from patients with stomach ulcer. Under pathology two coupled but opposite changes (simultaneous activation and inhibition) in succinate dependent Ca2+ transport occur. The inhibition of Ca2+ transport was detected by its elimination with glutamate, being mostly pronounced after cycle of ADP phosphorylation added to suspension of mitochondria. The treatment of animal with 2-oxoglutarate abolished this inhibition. This was not observed in healthy animals. The described phenomenon can prevent hyperactivation of succinate oxidation under strong pathological (distress) influences.

[Optimization of energy-dependent processes in mitochondria from rat liver and brain after inhalation of negative air ions]. / Optimizatsii énergozavisimykh protsessov v mitokhondriiakh pecheni i mozga krys posle vdykhaniia otritsatel'nykh aéroionov.

The effect of negative air ions (NAI) inhalation by rats on energy reactions of mitochondria in homogenates of liver and brain was studied. The influence of NAI was investigated under activation of animals by administration of physiological dose of adrenaline. Adrenaline administration induced hyperactivation of the rate of phosphorylating oxidation of succinic acid in liver and brain mitochondria which was accompanied by oxalacetate inhibition of succinate dehydrogenase (SDH) as well as excessive Ca2+ accumulation in liver mitochondria. These changes connected with a decrease of coefficient of phosphorylation efficiency ADP/O and uncoupler stimulation of respiration evidenced decrease of energy control of respiration in mitochondria. NAI inhalation diminished the rate of hyperactivated respiration and abolished excessive Ca2+ accumulation. These changes together with ADP/O coefficient and DNP stimulation increase evidence improvement of energy control of respiration which provide more moderate function of the respiratory chain under activation by adrenaline. Animals were excited by adrenaline administration. This effect was abolished by NAI inhalation, animals relaxed, some fell asleep. The data evidence sensitivity of mitochondrial processes in internal organs to inhalation of NAI and show participation of mitochondria in realization of physiological effects of NAI.

[Predicting heart failure by intravital study of the mitochondrial energy function in patients with heart defects]. / Prognoz serdechnoi nedostatochnosti po dannym prizhiznennogo izucheniia énergeticheskoi funktsii mitokhondrii u bol'nykh porokami serdtsa.

The mitochondrial energy system (respiration and oxidative phosphorylation) was studied in 144 patients by a lifetime method for polarographic recording of respiration of tissue sections in myocardial biopsy specimens. The application of new biochemical criteria for assessing the energy system of mitochondria increases the accuracy of diagnosis of latent heart failures in the presence of cardiac malformations.

[Liver mitochondrial participation in the body adaptation reactions in a rat heart transplant]. / Uchastie mitokhondrii pecheni v adaptatsionnykh reaktsiiakh organizma pri peresadke serdtsa u krys.

Alterations in coupling of respiration and phosphorylation as well as in energy-dependent transport of calcium in liver mitochondria of recipient were studied in dynamics of antigenic response to rat heart transplantation. As compared with the normal state the reactions studied varied in opposite directions, towards activation (hyperergic step) within 1-4 days after the heart transplantation and to decrease in their activity (hyperergic step) within 6-10 days; the latter period was characterized by development of the state similar to pathological one. Increased in amount of endogenous succinic acid as well as in succinate dehydrogenase activity were apparently among the other factors responsible for activation of energy metabolism in the hyperergic state. The reactions of liver mitochondria studied were identified as unspecific adaptation of the recipient liver tissue, which might be used for diagnosis of early steps of rejection crisis.