Nagibin V. Mechanisms of rat neonatal cardiomyocytes death in culture at modeling of anoxia-reoxygenation: the role of the proteasomal proteolysis.

This work is dedicated to the study of rat neonatal cardiomyocytes death in culture at modeling of anoxia-reoxygenation and to the methods of its prevention especially endogenous cardioprotection. It was shown that not only necrotic cell death but also some types of programmed cell death (as apoptosis and autophagic cell death) occur in cardiomyocytes culture at anoxia-reoxygenation modeling. The trying to decrease general myocardium injury by preventing of programmed types of cell death leads to dramatic increase in the number of necrotic cardiomyocytes and is not perspective way in cardioprotection. We first showed that all types of proteolytic activities of proteasome are decreased at anoxia and not completely restored at reoxygenation. The use of proteasomal inhibitors on this culture leads to the development of apoptotic and autophagic cell death programs. The role of the proteasome in the preconditioning and postconditioning development is investigated, and it was shown that small doses of proteasomal inhibitors can reproduce positive effects of these cardioprotective phenomena (decreasing of the number of necrotic and apoptotic but not autophagic cell death). We also have done the method of ischemic postconditioning reproducing in the rat neonatal cardiomyocytes culture. The new properties of well-known cardioprotector biophlavonoid quercetine and its water soluble form "Corvitine" are studied. It was shown that these biophlavonoids can inhibit proteasomal activity and as well as specific inhibitors of proteasome can be used to the pharmacologic reproducing of endogenous cardioprotection phenomena.