Intracellular Kinase Mechanism of the Cytoprotective Action of Adaptation to Chronic Hypoxia in Anoxia/Reoxygenation of Cardiomyocytes

On the model of anoxia/reoxygenation of isolated cardiomyocytes, we studied the role of kinases in the implementation of the cytoprotective effect of chronic continuous normobaric hypoxia (21 days on continuous exposure of rats at 12% O2). Anoxia/reoxygenation of cardiomyocytes from intact rats caused death of 16.5% cells, which was accompanied by the release of lactate dehydrogenase; in suspension of cardiomyocytes from adapted rats, only 6.8% cells died and the release of lactate dehydrogenase was lower by 60%. Incubation of cells with inhibitors of protein kinase C (chelerythrin, 10 mM), protein kinase Cδ (rottlerin, 1 μM), tyrosine kinases (genistein, 50 μM), but not with PI3K inhibitor (wortmannin, 100 nM) eliminated the cytoprotective effect of chronic continuous normobaric hypoxia. Thus, the cytoprotective effect of chronic normobaric hypoxia is realized through activation of protein kinase Cδ and tyrosine kinases, but not through PI3K.