Uspekhi Fiziologicheskikh Nauk最新文献

An exposure of the organism to several episodes of mild hypoxia results in the development of brain hypoxic/ischemic tolerance, as well as cross-tolerance to the stressful factors of psychoemotional nature. Such kind of preconditioning by mild hypoxia functions as “alarm signalization” by I.P. Pavlov, preparing the organism and, in particularly, brain to the forthcoming harmful event. Dose-dependent action of hypoxia on the brain can be considered as one particular case of the general phenomenon termed hormesis, or neurohormesis. Endogenous defense processes launched by the hypoxic preconditioning and leading to the development of cerebral tolerance are associated with activation of intracellular signal cascades, transcriptional factors, regulatory proteins and expression of pro-adaptive genes and their products in the susceptible brain regions. Important mechanism of systemic adaptation induced by hypoxic preconditioning includes modifications of pituitary-adrenal axis aimed at enhancement of its adaptive resources. All these components are involved in the neuroprotective processes in three sequential phases - initiation, induction, and expression. Important role belongs also to epigenetic mechanisms controlling the activity of pro-adaptive genes. In contrast to the preconditioning, hypoxic postconditioning is comparatively novel phenomenon and therefore its mechanisms are less studied. The involvement of hypoxia-inducible factor HIF-1, and non-specific protective processes as up-regulation of anti-apoptotic factors and neurotrophines.

Kirov State Medical Academy, Kirov The results of the 20-years studies of the presence in blood serum and other body fluids of endogenous modulators of adrenergic and M-cholinergic impact a A COMPONENT of humoral element of autonomic nervous system. The article is devoted to the endogenous sensitizer of beta-adrenergic receptor (ESBAR) - water-soluble low molecular weight substances, analogues of which are histidine, tryptophan, tyrosine, mildronat and preduktal. It is shown, that separate dilutions of human serum and animal (as a source of ESBAR) and ESBAR - analogues ways to enhance the effectiveness of activation of beta-adrenoceptors (AR) of smooth muscle (uterus, coronary and renal arteries, trachea, stomach), myocardium and erythrocytes and platelets (respectively influenced of histidine and tryptophan). It is reported? that content of ESBAR in human serum (according to the titers of its dilution) depends on the sex and the presence of somatic diseases, and at women are also on the stage of reproduction and obstetric complications It is discussed hossible mechanisms of ESBAR action, its physiological role, including as a component of beta-adrenoreceptor myometrium inhibitory mechanism, as well as the prospect of the use of analogues ESBAR, including for the prevention of preterm labor, and for the treatment of bronchial asthma, coronary heart disease, hypertension and heart failure.

The quality of mother-infant relationship in the early postnatal period influences the neurophysiology and behavior of adult animals via epigenetic mechanisms. The most studied target of long-term effects of early life events on physiology and behavior is hypothalamic-pituitary-adrenal axis, in particular, epigenetic programming of glucocorticoid receptor gene expression. Inhibition of histone deacetylases is a tool for epigenetic modulation of nervous system plasticity. Using this approach, it was demonstrated that epigenetic mechanisms play an important role in physiological and behavioral modifications. It is also promising tool for reversing the negative effects of disturbances in the mother-infant relationship early in life. To date, however, the use of histone deacetylase inhibitors is widespread in adult animals, while studies in the early postnatal period are still scarce despite their relevance.

Based on the process needs, motivations and emotions, are describing molecular, cellular and systemic mechanisms of goal-direction motivated behavior. Goal-direction behavior is impossible without the orientation in space and forming a cognitive map. This process implements the hippocampus, via the neocortical connections. The hippocampus is linked to the amygdala, which is involved in the implementation of emotional behavior and organizing emotionally intense cognitive map or context of the environment.

The article describes the role of transposable elements in the ontogenesis of eukaryotes. Adaptive and controlled transposition of mobile elements occurs at different stages of development of an organism, causing dramatic changes in the regulation of gene expression, representing a cascade of reactions inherited genome evolutionary fixed at the species level. At this cascade of reactions involved regulatory system of tissue-specific expression of proteins splice variants in connection with the role of adaptive genes mosaic structure to numerous transpositions and the interconnectedness of mechanisms their evolutionary stabilization. Important role in the transposition of mobile elements and their interaction with groups of genes play epigenetic mechanisms - DNA methylation, histone modification, the expression of non-coding RNA. The genome structures responsible for the epigenetic regulation can have a transposons origin. In contrast to the previously established hypotheses on transpositions of mobile elements in the ontogenesis as a chaotic process, causing the destabilization of genotype, with a modern viewpoint, this mechanism has a species-specific patterns, formed evolutionarily. Mechanisms of the evolutionary transformation of genomes by natural selection create a relatively stable complex regulatory epigenetic characteristics of transpositions in the process of individual development, acting among individuals of the same species. The stability of the complex genomic information regulation in ontogenesis provides a specific set of transposons. Changing this regulation set transposons can cause fatal for the development of events. Dysregulation of transposons, not involved in the developmental restructuring, can give the inheritance of these changes. The aging process is a consequence of the evolutionary relationship of species-specific features of the regulation of mobile elements in ontogenesis, aimed at continuity and continuous increase in living matter for maximum adaptability. In the overall scheme of ontogenetic development process can be described as a way to implement the established evolutionary genomic information in time by means of gradually stabilized complex interaction of regulators of transpositions of mobile elements of the genome with a differentiated pattern of gene expression and regulation of splicing variants of their products. These transpositions vary with each cell division, especially by implementing the expression of sets of genes, the products of which affect the nature of the further transposition and change of regulation in the subsequent stages of development of an organism.

Hormones of stress, glucocorticoids, regulate numerous physiological processes and functions. These hormonal effects involve diverse mechanisms of action. Glucocorticoid receptors (GRs) are transcription factors which regulate gene expression by canonical mechanism of the hormone action through interaction with specific nucleotide sequence (GRE) in the regulatory region of the gene. The effects of the canonical mechanism develop for several hours. Non-genomic rapid effects of the hormone emerged in seconds- minuets and supposed to be associated with yet not identified receptor in the plasma membrane. In addition to these slow and rapid hormonal actions, one more slow non-canonical mechanism of glucocorticoid action become increasingly evident. This mechanism is based on protein-protein interactions of GRs with other transcription factors. The main modern concepts of canonical, non-canonical and membrane mechanisms of hormone action are discussed in the review.

In recent decades, it has been found the existence of a new class of biologically active substances - gaseous mediators (gasotransmitters), performing in the cells the signaling function and with high specificity involved in the intercellular and intracellular communication. This review characterizes the main gasotransmitters: nitric oxide, carbon monoxide, hydrogen sulfide, sulfur dioxide and polysulfides. Their physiological role and involvement in the pathogenesis of diseases is described. Basic information about main gasotransmitters is generalized in the original table. Nitrate-Nitrite background, which is a chemical background of the existence of modern man, affects the intra- and intercellular signaling system, alters the ultrastructure of neurons, neuron-neuron and neuron-glia interaction, eliminates the effects of endogenous gasotransmitters and affects the average life expectancy. In accordance with the principle of cyclicity is proposed and substantiated the hypothesis of the existence of “hydrogen sulfide cycle”, combining three sulfur-containing gasotransmitters. It is suggested that the cyclic organization of gasotransmitters in the cells and the whole body can be due to the existence of a global principle of cyclicity, which can spread its influence on almost all the structural and functional levels in the animate and inanimate nature.

Cell-to-cell communications and autocrine/paracrine regulations are mediated by an extracellular signaling network involving secretion of a variety of different factors, hormones, neurotransmitters, and other signaling molecules that are recognized in an extracellular medium by multiple molecular receptors operating in the plasma membrane of cells. Most of plasma membrane receptors belong to the superfamily of heptahelical receptors, many of which are coupled by G-proteins to adenylate cyclase responsible for cAMP production in the cell cytoplasm. The canonical role of cAMP in cell physiology is to serve as a second messenger and universal regulator of intracellular processes. Meanwhile, increasing body of evidence leaves little doubts that stimulated cells can release cAMP into intercellular space, where it may serve as signaling molecule in cell-to-cell communications and autocrine regulations. This review considers the basic concept on mechanisms of intracellular and extracellular signaling with cAMP as the second and first messenger.

Literature and our data suggest the regulatory action of a number of biologically active substances (catecholamines, cardiac glycosides, β-blockers, angiotensin-converting-enzyme inhibitor) on the growth and proliferation of heart cells. By using of organotypic tissue culture has proved that the basis of this regulation is the ability of test substances, receptor- or transducer-mediated signaling to modulate the function of Na⁺, K⁺-ATPase. There is a delay in the development of vascular smooth muscle in the late postnatal period in rats with the blockade of the sympathetic nervous system in the prenatal period. The relationship between vascular remodeling and contractile activity is described. It seems that one of the causes of high blood pressure is a remodeling of the cardiovascular system, which precedes the development of hypertension.