title: High-dose alcohol induces reactive oxygen species-mediated apoptosis via PKC-β/p66Shc in mouse primary cardiomyocytes.
abstract: Cardiac dysfunction caused by excessive alcohol consumption is a specific disease, alcoholic cardiomyopathy (ACM). High-dose alcohol has been found to induce oxidation stress and apoptosis in cardiomyocytes, but the signaling link between alcohol-induced oxidation stress and apoptosis in cardiomyocytes remains to be elucidated. To address the issue, we exposed primary cardiomyocytes from neonatal mouse hearts to high doses of alcohol (50mM, 100mM, and 200 mM). We found that alcohol induced dose-dependent phosphorylation of p66shc, and reactive oxygen species (ROS) production increased in parallel with phosphorylation levels of p66shc. Exposure to alcohol also led to loss of mitochondrial membrane potential and cytochrome c release. Depletion of p66Shc and inhibition of protein kinase C-β (PKC-β) successfully reversed all the effects and suppressed alcohol-induced apoptosis in cardiomyocytes. Collectively, our study provides a molecular basis for signaling transduction of alcohol-induced oxidation stress and apoptosis of cardiomyocytes, which may facilitate the prevention and treatment of ACM.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yayan
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chi
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. Electronic address: xinxueguan0451@163.com.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002310:Cardiomyopathy, Alcoholic / Q000201:enzymology / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress; D010766:Phosphorylation; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000431:Ethanol; C099154:ruboxistaurin; D045304:Cytochromes c; D064546:Protein Kinase C beta
keywords: Alcoholic cardiomyopathy; Apoptosis; Cardiomyocyte; Protein kinase C-β; Reactive oxygen species; p66shc