Epoxyeicosatrienoic acids protect cardiac cells during starvation by modulating an autophagic response.

Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase metabolites of arachidonic acid involved in regulating pathways promoting cellular protection. We have previously shown that EETs trigger a protective response limiting mitochondrial dysfunction and reducing cellular death. Considering it is unknown how EETs regulate cell death processes, the major focus of the current study was to investigate their role in the autophagic response of HL-1 cells and neonatal cardiomyocytes (NCMs) during starvation. We employed a dual-acting synthetic analog UA-8 (13-(3-propylureido)tridec-8-enoic acid), possessing both EET-mimetic and soluble epoxide hydrolase (sEH) inhibitory properties, or 14,15-EET as model EET molecules. We demonstrated that EETs significantly improved viability and recovery of starved cardiac cells, whereas they lowered cellular stress responses such as caspase-3 and proteasome activities. Furthermore, treatment with EETs resulted in preservation of mitochondrial functional activity in starved cells. The protective effects of EETs were abolished by autophagy-related gene 7 (Atg7) short hairpin RNA (shRNA) or pharmacological inhibition of autophagy. Mechanistic evidence demonstrated that sarcolemmal ATP-sensitive potassium channels (pmKATP) and enhanced activation of AMP-activated protein kinase (AMPK) played a crucial role in the EET-mediated effect. Our data suggest that the protective effects of EETs involve regulating the autophagic response, which results in a healthier pool of mitochondria in the starved cardiac cells, thereby representing a novel mechanism of promoting survival of cardiac cells. Thus, we provide new evidence highlighting a central role of the autophagic response in linking EETs with promoting cell survival during deep metabolic stress such as starvation.

[Role of trehalose and glycogen in the survival of aging Saccharomyces cerevisiae cells]. / Rol' tregalozy i glikogena v podderzhanii zhiznesposobnosti stareiushchikh kletok Saccharomyces cerevisiae.

The role of the storage carbohydrates trehalose and glycogen in the survival of aging Saccharomyces cerevisiae cells was studied. Culture aging for one week did not reduce cell viability. During this period, the cells accumulated the storage carbohydrates and raised the activity of the glycolytic enzymes hexokinase and phosphofructokinase. However, further aging led to a drastic drop in cell viability and to a decrease in the cellular content of trehalose and glycogen and in the activity of hexokinase and phosphofructokinase. The possible reasons for these changes are discussed.

Inhibition of Krebs cycle and activation of glyoxylate cycle in the course of chronological aging of Saccharomyces cerevisiae. Compensatory role of succinate oxidation.

We investigated oxidative processes in mitochondria of Saccharomyces cerevisiae grown on ethanol in the course of chronological aging. We elaborated a model of chronological aging that avoids the influence of exhaustion of medium, as well as the accumulation of toxic metabolites during aging. A decrease in total respiration of cells and, even more, of the contribution of respiration coupled with ATP-synthesis was observed during aging. Aging is also related with the decrease of the contribution of malonate-insensitive respiration. Activities of citrate-synthase (CS), alpha-ketoglutarate dehydrogenase (KGDH) and malate dehydrogenase (MDH) were threefold decreased. The activity of NADP-dependent isocitrate dehydrogenase (NADP-ICDH) decreased more significantly, while the activity of NAD-dependent isocitrate dehydrogenase (NAD-ICDH) fell even greater, being completely inactivated on the third week of aging. In contrast, succinate dehydrogenase (SDH), enzymes of glyoxylate cycle (GCL) (isocitrate lyase (ICL) and malate synthase (MLS)), and enzymes of ethanol oxidation (alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ACDH)), were activated by 50% or more. The behavior of oxidative enzymes and metabolic pathways are apparently inherent to a more viable, long-lived cells in population, selected in the course of chronological aging. This selection allows cells to reveal the mechanism of their higher viability as caused by shunting of complete Krebs cycle by glyoxylate cycle, with a concomitant increased rate of the most efficient energy source, namely succinate formation and oxidation. Thiobarbituric-reactive species (TAR species) increased during aging. We supposed that to be the immediate cause of damage of a part of yeast population. These data show that a greater succinate contribution to respiration in more active cells is a general property of yeast and animal tissues.

[Effect of a low concentration of hydrogen peroxide on metabolism of blood cells]. / Vliianie nizkoi kontsentratsii perekisi vodoroda na metabolizm kletok krovi.

Hydrogen peroxide is known to posses a wide range of physiological effects towards functional activity of cells. We have investigated the influence of H2O2 on the activity of glycolys in the native blood cells. Adding of hydrogen peroxide up to final concentration 50 microM led to decrease of activity some glycolytic enzymes. H2O2 inhibited consumption of glucose by blood cells. Despite the fact that H2O2 is well known as prooxidant, we observed decrease of the level of thiobarbituric acid reactive species in the blood cells after their incubation in the presence of hydrogen peroxide for 2 hours. Based on these data we supposed that effects of hydrogene peroxide occur via signal transduction pathways.

[Arsenite-induced lipid peroxidation in Saccharomyces cerevisiae]. / Arsenit kak induktor processov perekisnogo okisleniia lipidov v kletkakh drozhzhei Saccharomyces cerevisiae.

The ability of sodium arsenite at concentrations of 10(-2), 10(-4), and 10(-6) M to induce lipid peroxidation in Saccharomyces cerevisiae cells was studied. Arsenite at the concentrations 10(-2) and 10(-4) M enhanced lipid peroxidation and inhibited the growth of yeast cells. Enhanced lipid peroxidation likely induced oxidative damage to various cellular structures, which led to suppression of the metabolic activity of cells. Arsenite at the concentration 10(-6) M did not activate lipid peroxidation in cells. All of the tested arsenite concentrations inhibited the activity of alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase in cells. The inference is made that the toxicity of arsenite may be related to its stimulating effect on intracellular lipid peroxidation.

[Intersystemic functional integration under the action on the body of electromagnetic factors]. / Mezhsistemnaia funktsional'naia integratsiia pri deistvii na organizm faktorov élektromagnitnoi prirody.

Frequency zones of the brain electrical activity, heart rate and respiration were studied through certain parameters characterised by individual asymmetry and low but stable intersystemic integration. Chronic electromagnetic irradiation reduced a resistance against an emotional stress as manifested in a "decay" of individual spatial-temporal infrastructure of informational parameters of the EEG, heart rate and respiration.

[An ethological approach in the study of nonverbal communication in man and chimpanzee]. / Etologicheskii podkhod v izuchenii neverbal'noi kommunikatsii u cheloveka i shimpanze.

The nonverbal communication of man and chimpanzee has been studied. Sexual dimorphism of nonverbal communication patterns, which is connected with the definite contexts of behavior are revealed. Possible ways of evolution in communication systems i shown. This analysis will permit to apply the data of ethological investigation of nonverbal behavior as sexual marker in diagnosis of different groups of mentally ill patients.

[Treatment of fractures of long tubular bones associated with cranio-cerebral injuries]. / Lechenie perelomov dlinnykh trubchatykh kostei, sochetannykh s cherepno-mozgovoi travmoi.

Based on an analysis of treatment of 166 patients with fractures of long tubular bones associated with cranio-cerebral trauma the authors discuss tactics of treatment of injuries of the locomotor apparatus. In patients with critical cranio-cerebral traumas at the early period of trauma disease of the brain fractures should be treated by sparing methods, Ilizarov's apparatus included. The operations on the bones should be performed on indications not earlier than 3-4 weeks after trauma.

[Schizophrenic syndromes and efficacy of unilateral electroconvulsive therapy]. / Sindromy shizofrenii i éffektivnost' unilateral'noi élektrosudorozhnoi terapii.

The authors compared the efficacy of unilateral electroconvulsive therapy in schizophrenia in relation to the leading syndrome and the place of electrode application. In controlling the affective and catatonic syndromes the best effect was achieved when the electrodes were applied to the non-dominant hemisphere. In delirious, hallucinatory-delirious and hallucinatory syndromes, the maximal effect was achieved by the application of electrodes to the dominant hemisphere. The relationship between the effect of local electroconvulsive therapy and the semiotics of the syndromes allows making the most rational use of unilateral electroconvulsive therapy in the differential treatment of schizophrenia.

[Age and the tempo of the progression of alcoholism in patients with a history of alcoholic delirium]. / Vozrastnoi patomorfoz tempa progredientnosti alkogolizma u bol'nykh, perenesshikh alkogol'nyi delirii.

The differentiation of psychotic and non-psychotic forms of alcoholism on the basis of the epidemiological data on some clinical characteristics of alcohol pathology over the period of 1975-1982 has shown that the pathomorphism of the clinical manifestations of alcoholism and alcoholic psychosis depends on a complex of social and biological factors. A more considerable involvement of biological factors in determining the age of the onset of alcohol psychoses has been demonstrated. The clinico-anthropometric and clinico-statistical studies of 230 alcoholics of two age groups with a history of delirium tremens has prompted the conclusion as to a considerable influence of the age factor on the change in the clinical picture of the disease and its progression.