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Registration Number

0216U003072, 0110U000694 , R & D reports

Title

Molecular chaperon as a universal regulators of stress-indused signalling pathways cardiomyocytes

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Head

Sidorik L.L.,

Registration Date

12-01-2016

Organization

Institute of Molecular Biology and Genetics

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A large array of data obtained from studies in vitro and in vivo, indicating the leading role of apoptosis in morphogenesis of the heart and the pathophysiology of cardiovascular diseases. For the heart is typical recently described a unique type of programmed cell death infarction - the so-called "apoptosis interrupted or incomplete", characterized caspase cascade without visible changes in the kernel. Among the key regulators of apoptosis caspase inhibitors identified, growth factors, calcium and oxidants, Bcl-2 family of proteins and anti-stress proteins (heat shock proteins, molecular chaperones). Established that the correct protein folding depends on the functioning of specialized family vysokokonservatyvnyh anti-stress proteins - molecular chaperones (HSPs). HSPs overexpression is a powerful tool tsytoprotektsiyi, including the cardiovascular system. Another important anti-apoptosis pathway that supports the livelihoods kardiomyotsytiv is primarily associated with the activation of insulin receptor that triggers the PI3K / PDK / AKT / mTOR / p70S6K protein kinase cascade. p70S6K kinase is an important regulator of the speed and efficiency of biosynthesis of proteins critical in the physiological adaptation to stress infarction, in which the activated PI3K-way. Akt1 proteinkinaza when activated causes myocardial protection from ischemia in vivo. Akt1 is activated PI3K kinazoy and plays an important role in the vital activity of cells - blocking caspase function which - providing apoptosis program. We investigated the structural and functional aspects of molecular chaperones Hsp60 vzayemodiyiyi and Hsp90 r70S6K1 of kinases Akt1 and methods of co-imunopetsypitatsiyi and pool-Down analysis and quantitative changes in the level and cellular localization of these proteins in the hearts of mice model of experimental myocarditis progression-shaped and DKM- such methods imunoblotynhu pathology and immunohistochemistry. There were no significant changes in the expression of Akt1 in both cases, no pathologies at the gene or protein level. However, we found significant and credible changes in the level of Akt1 phosphorylation in the myocardium of mice in the final stage of heart failure progression inducible (DCM-like disease). The first time the changes in expression and cellular localization of Hsp60 and shaperoninu r70S6K1 kinase, Akt1 in the heart of model mice with the progression of heart failure on inducible models of both phases of experimental heart failure. It is shown that Hsp60 levels were significantly higher in the final stage of myocarditis progression than DCM; for Hsp90 - on the contrary, which may indicate the involvement of chaperones differences in the regulation of cardiac myocytes in progression syhnalinhu two phases CH. Based on the obtained our data and literature data suggested working model to attract shaperoninu Hsp60 and chaperone Hsp90 in regulation of stress-induced syhnalinhu cardiomyocytes in progression CH by creating dynamic functional complexes of kinase p70S6K1, on the one hand, and of Akt1 kinase, on the other, that, in turn, can determine what type of programmed cell death is induced in cardiomyocytes.

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І.В. Крупська
Бобик В.І.
Вігонтіна О.Г.
Заєць В.М.
Маркелова О.Ю.
Яковенко Л.Ф.

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2020-04-02