Insulin-like growth factor I retards apoptotic signaling induced by ethanol in cardiomyocytes

Apoptosis of cardiac muscle cells may contribute to the development of cardiomyopathy and heart failure, Alcohol (ethanol) abuse is a major cause of cardiomyopathy, but its underlying mechanism remains unknown. To determine whether ethanol causes apoptosis in cardiac muscle and whether insulinlike growth factor I(IGF I) improves cardiac muscle survival upon ethanol exposure, we have defined the effects of ethanol and IGF I in primary cardiomyocytes, Ethanol decreased cell viability in dose-response manner from 0.2% to 1%. In contrast, ethanol (0.2-1%) did not alter viability of cardiac fibroblasts. To assess the occurrence of apoptosis, DNA fragmentation was determined with quantitation of nucleosomes, Nucleosomes were increased in ethanol-treated cells, thus confirming the apoptotic effects of ethanol. The pro-apoptotic Bar protein and Caspase 3 are important proteins of apoptotic signaling. The content of Bar and the activities of Caspase 3 were increased upon ethanol exposure. IGF I partially suppressed fax induction, Caspase 3 activation, DNA fragmentation, and increased cardiomyocyte survival. The effects of IGF I on ethanol-induced apoptosis can be inhibited with a chemical inhibitor of PI 3 Kinase (LY-294002), suggesting that anti-apoptotic actions of IGF I involves PI 3 Kinase, These results may have important implications on further understanding the pathogenesis of alcoholic heart disease and the development of new strategies to treat alcoholic cardiomyopathy. (C) 2000 Elsevier Science Inc. All rights reserved.