title: Insulin-like growth factor I retards apoptotic signaling induced by ethanol in cardiomyocytes.
abstract: 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 insulin-like growth factor I (IGF 1) 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 Bax protein and Caspase 3 are important proteins of apoptotic signaling. The content of Bax and the activities of Caspase 3 were increased upon ethanol exposure. IGF I partially suppressed Bax 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.
authors.affiliation: Villa Park High School, CA, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: P H
authors.initials: PH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003470:Culture Media; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051028:bcl-2-Associated X Protein
chemical_list: D053148:Caspase 3; D020169:Caspases; D002867:Chromones; D003470:Culture Media; D004791:Enzyme Inhibitors; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D009025:Morpholines; D009707:Nucleosomes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C505410:Casp3 protein, rat