[The physiological significance of regulation by catecholamines, second messengers and enzyme inducers of glutathione metabolism]. / Fiziologicheskoe znachenie reguliatsii katekholaminami, vtorymi posrednikami i induktorami fermentov metabolizma glut5ationa.

Stress, catecholamines (CA), cAMP and protein-kinase A do not affect superoxide dismutase, catalase, thioredoxin reductase, thiol transferase and glutathione reductase (GR). However, they activate glutathione peroxidase and glutathione transferase (GT) in a number of organs and inhibit renal gamma-glutamyl transferase. Ca2+ ions activate GT through calmodulin. CA were found to stimulate GSH transport from liver to blood and GT phosphorylation by protein kinase C. This suggests a regulation of the GSH metabolism by hormones and a second messenger. This regulation favours metabolism of active O2 substances (including protection from peroxide stress and leukotriene C4 synthesis), supporting of SH-proteins in reduced state, xenobiotics detoxication. GT and GR induction can play an important role in the mechanism of anti-peroxide action of butylhydroxytoluene.

[Regulation of various isoenzymes of glutathione transferases of protein kinase A and cAMP]. / Reguliatsiia razlichnykh izofermentov glutationtransferazy proteinkinazoi A i cAMP.

Activation of purified glutathione transferase (CE 2.5.1.18) from the rabbit liver by cAMP-dependent protein kinase (protein kinase A) and activation of glutathione transferase from the rat liver and heart by cAMP preparations have been studied. A comparison of glutathione transferase activation on different substrates and the results of the inhibitor analysis of the activation phenomenon have shown that the second (mu) family of glutathione transferase isoenzymes (subunits, 3, 4, 6) is the most probable object of regulation. The first (alpha) family (subunits 1 and 2) and isoenzyme 5-5 are not probably regulated.

[The effect of phenobarbital, ionol and cAMP on the activity of glutathione metabolism enzymes in rodents]. / Vliianie fenobarbitala, ionola i cAMP na aktivnost' fermentov metabolizma glutationa u gryzunov.

The phenobarbital and ionol administration to rats and mice increases considerably the glutathione transferase, glutathione reductase and gamma-glutamyl transferase activities in the liver. The induction of these enzymes has been observed in a number of experiments in the heart and kidney but it was less pronounced. A correlation was established between the induction of glutathione transferase, glutathione reductase and gamma-glutamyl transferase, their changes in mice and rats, phenobarbital and ionol effects. The stimulatory effect of cAMP on glutathione transferase in the liver (and in a number of experiments in the heart) increased against a background of the both agents. The cAMP-dependent activation of glutathione peroxidase was retained in the heart but in some series experiments it disappeared in the liver and kidney. Mechanisms of the long-term (induction) and short-term (cAMP) elevation of the glutathione transferase and glutathione peroxidase activities functioned independently and often in concord. It is suggested that induction of glutathione metabolism enzymes may play an important role in biological effects of ionol.

[Classification of drugs by biochemical mechanism of action]. / Klassifikatsiia lekarstv po biokhimicheskim mekhanizmam deistviia.

Biochemical drugs classification is proposed. Drugs are divided into 6 classes, according to their action on: 1) signal-transduction systems, 2) other components of plasmatic membranes, 3) intracellularly, 4) gene therapy, 5) extracellularly, 6) invasive agents. Concrete biochemical mechanisms of action of every class drugs are considered and described.

[Study of mechanisms of regulation of disulphide reductase in mouse liver]. / Issledovanie mekhanizmov reguliatsii disul'fidreduktaznoi sistemy pecheni myshi

An increase in activity of disulphide reductase system (DRS) in supernatant of liver tissue was caused by 3',5'-AMP, ATP, GTP, UTP, Mg2+, Ca2+, EDTA, protamine, noradrenaline and F-. The effect was connected with arsenite resistant fraction of DRS. After rapid homogenization the effect of noradrenaline disappeared and the effects of ATP, GTP, UTP and Ca2+ were distinctly decreased. Treatment with adsorbents prevented the effects of 3',5,-AMP, ATP and EDTA and markedly decreased the effects of protamine and Mg2+. A protein inhibitor of protein kinase prevented completely the activation of DRS with 3',5'-AMP, ATP, GTP, UTP and noradrenaline and distinctly decreased the effect of protamine, Mg2+ and Ca2+ but did not alter the influence of EDTA. Addition of 2',3'-AMP blocked the effect of 3',5-AMP, ATP and Mg2+ but did not influence the effect of protamine and EDTA. The data obtained suggest that protein kinase participated in activation of DRS by most of the regulators.

[Catecholamines: biochemistry, pharmacology, physiology, clinical aspects]. / Katekholaminy: biokhimiia, farmakologiia, fiziologiia, klinika.

Catecholamines (CAs) realise activity of certain cerebral neurons, sympathoadrenal system and peripheral cells producing dopamine. CAs control metabolism, template biosynthesis, cytological, physiological and psychological processes. During recent 10-15 years complex employment of various interdisciplinary approaches (including molecular biology techniques) resulted in some important achievements. Cellular transporters and 10 individual receptors were discovered and studied. Basic mechanisms of CA signal transduction into nucleus and mitochondria, regulation of gene expression, hyperplasia, hypertrophy and biological oxidation have been recognised. It was found that besides central neurotransmitter action DA also acts as peripheral auto- and paracrinic hormone. CA participate in pathogenesis of many illnesses and in the defence mechanisms of a body. CA and related substances are effective and widely used drugs.

[Amino acids and their metabolites in blood and urine of children with minimal cerebral dysfunction]. / Aminokisloty i ikh metabolity v krovi i moche pri minimal'noi tserebral'noi disfunktsii u detei.

The following changes were found in children in the minimal cerebral dysfunction: the hypoaminoacidemia and hypoaminoaciduria with decrease of glutamate and aspartate, their amides, methionine and serine in the blood and urine; decrease of lysine, taurine, tyrosine, catecholamines and serotonin in the blood; increase of GABA and glycine in the blood; increase of xanthurenate, proline and cysteine in the urine. The ratio excitatory/inhibitory mediatory amino acids decreased significantly. The ratio essential/nonessential amino acids and concentrations of amino acids, transporting by x-AG, beta and A/ASC systems, decrease in the blood; majority of transporting systems in the kidney functions augmently. Disturbances of amino acids metabolism disappear or decrease in successful treatment.

[Effect of emotional stress on the activity of enzymes of glutathione metabolism]. / Vliianie émotsional'nogo stressa na aktivnost' fermentov metabolizma glutationa.

Emotional stress during 20 min induced the stimulation of the glutathione peroxidase activity in heart, liver and kidney tissues and the activation of glutathione-S-transferase in heart and liver tissues. gamma-Glutamyl transferase activity was inhibited in liver and kidney tissues. The alterations were gradually decreased in heart greater than or equal to liver greater than kidney. Both catecholamines (in vivo) and cAMP (in vitro) produced the same effects. Close correlation between the stress and cAMP actions on the glutathione metabolizing enzymes was found. No changes of glutathione reductase activity was observed in all the tissues studied.

[Activity of enzymes of glutathione metabolism and regulation by cAMP in human tumors]. / Aktivnost' fermentov metabolizma glutationa i ikh reguliatsiia tsAMF v opukholiakh cheloveka.

Tumors were studied in 38 patients, tissues located far away from tumor being used as control. Breast and stomach tumors revealed relatively high levels of glutathione reductase, glutathione-S-transferase (I) and, particularly, gamma-glutamyl transferase (II). The said changes were not observed in colorectal tumors. Gamma-glutamyl transferase (II) may be used as a marker for breast and stomach malignancies in man but it is not a universal and absolutely specific marker for all tumors. The activity of glutathione peroxidase (III) either did not change or decreased. The activating effect of cAMP on III and I remained generally unchanged in all tumors studied.

[The effect of emotional-painful stress, hypoxia, and adaptation to it on the activity of enzymes for metabolizing glutathione and concentration of glutathione in rat organs]. / Vliianie émotsional'no-bolevogo stressa, gipoksii i adaptatsii k nei na aktivnost' fermentov metabolizma glutationa i kontsentratsiiu glutationa v organakh krys.

The stress activates glutathione peroxidase in the heart, liver, and kidney, glutathione transferase in the heart and liver, inhibits gamma-glutamyl transferase in the liver; the activity of glutathione reductase and the content of reduced glutathione were unchanged. Two-four-minute hypercapnic hypoxia unchanged the activity of glutathione metabolic enzymes. The activity of the above enzymes decreases in some organs at the death caused by 2-15-minute hypoxia. Long-term intermittent adaptation to hypobaric hypoxia lowers the activity of glutathione peroxidase, -transferase and -reductase. The biological value of the two types of enzymatic responses may be different: stress-induced activation of glutathione metabolic enzymes can enhance resistance to stress and xenobiotics; however, their inhibition during hypoxic adaptation may produce the opposite effect.

[Influence of alpha-lipoic acid on liver glutathione system of healthy and Ehrlich ascites carcinoma transplanted mice].

Influence of alpha-lipoic acid (LA) on liver glutathione system of Ehrlich ascites carcinoma (EAC) transplanted mice was studied. LA causes multidirectional influence on glutathione system of healthy mice. EAC transforms LA influence, strengthening prooxidative effects more expressed at introduction in early terms after inoculation of the tumor. The mechanism explaining realization of LA prooxidative effects as a result of interaction with glutathione system is suggested.

[Catecholamines and their metabolites in children with Asperger and Kanner syndromes].

Children with Asperger and Kanner syndromes in the stable state demonstrate similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine and by an increase in dopamine and homovanylic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome in the aggravated state plasma MHPG increases, excretion of tyrosine decreases and excretion of normetanephrine increases. The observed imbalance in dopamine and epinephrine/norepinephrine systems justifies combined analysis of changes in catecholamines and their metabolites levels as the most informative approach in the study of the effect of autistic disorders.

[Nuclear glutathione and its functions].

During recent years the nuclear localization of glutathione has been confirmed and this fraction has been quantitatively determined. The nuclear GSH and the enzymes of its metabolism realize independent and important functions. They considerably differ from functions of hyaloplasmic and mitochondrial GSH. Glutathione interacts with regulatory pathways, involved into signal transmission into the nucleus.

[Glutathione system. I. Synthesis, transport, glutathione transferases, glutathione peroxidases].

Studies of glutathione system in all basic trends have been extended considerably during recent 10-15 years. A series of new metabolic enzymes has been discovered. Many of them are polyfunctional and their new activities have been recognized. The enzymes interact with hormones and signal transduction systems. The studies of intracellular, intercellular and inter organs transports have been considerably advanced. The important achievement consist in unmasking new functions not only by selective substances-analytics but also by gene engineering methods as well.

[Glutathione system. II. Other enzymes, thiol-disulphide metabolism, inflammation and immunity, functions].

The great significance of glutathione as a redox regulator and the reducing carrier has been established. There is a clear necessity for subdivision of an independent mitochondrial glutathione subsystem. The data on a specificity of glutathione metabolism in different organs are accumulated. The significance of glutathione system for inflammation and immunity has been proved. The investigations of glutathione system for elucidation of pathogenesis of diseases and its diagnostics are used in medicine.

[The blood glutathione system in cerebral vascular diseases and its treatment with alpha-lipoic acid].

The changes of glutathione metabolism are rare in dyscirculatory encephalopathy and ischemic stroke (IS) of mild severity. The frequent and considerable changes have been revealed in IS of moderate and high severity as well as in hemorrhagic stroke. An increase of activities of glutathione peroxidase and glutathione transferase is the most typical. The increase of enzyme activity was not observed at the beginning of treatment after 3 days and in patients with severe degree of disease who died later. A standard therapy decreased the quantity and/or expression of changes of the glutathione metabolism in patients with IS of moderate and high severity while the addition of alpha-lipoic acid (alpha-LA) led to the complete normalization in IS of moderate severity and normalization of most parameters in IS of high severity. The increase of functional activity of the glutathione system at the early stage of treatment of IS and the favorable changes during the treatment, in particular after the addition of alpha-LA, were correlated with the improvement of neurological status assessed with the NIHSS. It has been confirmed that the glutathione system plays an important role in the tolerance to brain ischemia.

Mitochondrial glutathione.

Many functions of mitochondrial GSH are significantly different from those of cytosolic GSH. This review considers the peculiarity of functions of mitochondrial GSH and enzymes of its metabolism, especially glutathione peroxidase 4, glutaredoxin 2, and kappa-glutathione transferase.

[Glutathione system in erythrocytes and plasma in viral hepatitis].

In all 5 acute (AVHs) and chronic viral hepatites (CVHs) there was the increase of erythrocyte activities of glutathione peroxidase (GPx) and glutathione reductase (GR), and the decrerase in GSH concentration. In blood plasma there was accumulation of GPx, glutathione S-transferase (GST) and y-glutamyl transferase (gammaGT). GSH and GR increased in plasma only in AVHs. In CVH C erythrocyte GST increased. Evidently changes in the erythrocyte glutathione system are reactions to oxidative stress and in blood plasma they are consequences of inflammation and hepatocyte cytolysis. Changes were more pronounced in middle-heavy course than in the heavy one. These changes have pathogenic importance and can be used in addition to complex diagnostics. They are significantly differed from changes in chronic gall-bladder diseases. Necessity of separate investigation of glutathione system in erythrocytes and blood plasma but not in whole blood is argued.

[Glutathione system in erythrocytes and blood plasma in strokes and dyscirculatory encephalopathy].

In dyscirculatory encephalopathy and moderate ischemic stroke there are single changes of components of glutathione metabolism. In moderate and severe ischemic stroke frequent and considerable changes have been revealed. Changes in hemorrhagic stroke are also expressed. An increase of activities of glutathione peroxidase and glutathione transferase is the most typical, rarely the increase of glutathione reductase and GSH is observed. The increase of enzymes activity was absent at the delayed oneset of treatment (more than 3 days) and in severe cases patients who died later. Glutathione system is important in the tolerance to cerebral ischemia.