title: Targeting Pin1 Protects Mouse Cardiomyocytes from High-Dose Alcohol-Induced Apoptosis.
abstract: Long-term heavy alcohol consumption is considered to be one of the main causes of left ventricular dysfunction in alcoholic cardiomyopathy (ACM). As previously suggested, high-dose alcohol induces oxidation stress and apoptosis of cardiomyocytes. However, the underlying mechanisms are yet to be elucidated. In this study, we found that high-dose alcohol treatment stimulated expression and activity of Pin1 in mouse primary cardiomyocytes. While siRNA-mediated knockdown of Pin1 suppressed alcohol-induced mouse cardiomyocyte apoptosis, overexpression of Pin1 further upregulated the numbers of apoptotic mouse cardiomyocytes. We further demonstrated that Pin1 promotes mitochondria oxidative stress and loss of mitochondrial membrane potential but suppresses endothelial nitric oxide synthase (eNOS) expression in the presence of alcohol. Taken together, our results revealed a pivotal role of Pin1 in regulation of alcohol-induced mouse cardiomyocytes apoptosis by promoting reactive oxygen species (ROS) accumulation and repressing eNOS expression, which could be potential therapeutic targets for ACM.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Inpatient Abdominal Ultrasonography, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Zizhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D000431:Ethanol / Q000633:toxicity*; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000431:Ethanol; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse