Protective effect of autophagy in anoxia-reoxygenation of isolated cardiomyocyte?
Preconditioning and postconditioning increased numbers of living cells and decreased that of necrotic, apoptotic and autophagic cells in anoxia-reoxygenation of isolated cardiomyocytes. It was established that proteasome inhibitors prevented the necrotic and apoptotic cell death of cardiomyocytes in anoxia-reoxygenation and in such a way reproduce the effect of pharmacological preconditioning and postconditioning. In this case, the population of autophagic cardiomyocytes has not changed considerably or had a tendency of increasing compared to anoxia-reoxygenation. The data obtained showed that the specific protective effect of proteasome inhibitors could be caused by autophagy activation. In our recent experiments new data supporting this hypothesis were obtained. The inhibition of autophagy with N-3-methyladenine during anoxia-reoxygenation caused an increase in the number of necrotic cells and a decrease of the live cell population. Moreover, simultaneous inhibition of both autophagy and apoptosis (N-3-methyladenine and caspase-3 inhibitor application) in anoxia-reoxygenation led to a dramatic increase of necrotic cardiomyocytes and a concomitant decrease in the number of living cells. Thus, the process of autophagy in cardiomyocytes during anoxia-reoxygenation may lead not only to programmed cell death, but has also some protective effect. The mechanisms of this phenomenon are still in need of thorough investigation.
Dosenko
Victor E
VE
Department of Experimental Cardiology, Bogomoletz Institute of Physiology, Kiev, Ukraine. dosenko@biph.kiev.ua
Nagibin
Vasyl S
VS
Tumanovska
Lesya V
LV
Moibenko
Alexey A
AA
D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D000860:Hypoxia; D019157:Ischemic Preconditioning, Myocardial; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats
D061945:Caspase Inhibitors; D061988:Proteasome Inhibitors; C025946:3-methyladenine; D000225:Adenine; D010100:Oxygen