title: Uncoupling protein 2 regulates palmitic acid-induced hepatoma cell autophagy.
abstract: Mitochondrial uncoupling protein 2 (UCP2) is suggested to have a role in the development of nonalcoholic steatohepatitis (NASH). However, the mechanism remains unclear. Autophagy is an important mediator of many pathological responses. This study aims to investigate the relationship between UCP2 and hepatoma cells autophagy in palmitic acid- (PA-) induced lipotoxicity. H4IIE cells were treated with palmitic acid (PA), and cell autophagy and apoptosis were examined. UCP2 expression, in association with LC3-II and caspase-3, which are indicators of cell autophagy and apoptosis, respectively,was measured. Results demonstrated that UCP2 was associated with autophagy during PA-induced hepatic carcinoma cells injury. Tests on reactive oxygen species (ROS) showed that UCP2 overexpression strongly decreases PA-induced ROS production and apoptosis. Conversely, UCP2 inhibition by genipin or UCP2 mRNA silencing enhances PA-induced ROS production and apoptosis. Autophagy partially participates in this progress. Moreover, UCP2 was associated with ATP synthesis during PA-induced autophagy. In conclusion, increasing UCP2 expression in hepatoma cells may contribute to cell autophagy and antiapoptotic as result of fatty acid injury. Our results may bring new insights for potential NASH therapies.
authors.affiliation: Department of Pathophysiology, Capital Medical University, 10 You An Men Wai Xi Tou Tiao, Beijing 100069, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Pathophysiology, Capital Medical University, 10 You An Men Wai Xi Tou Tiao, Beijing 100069, China.
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Capital Medical University, 10 You An Men Wai Xi Tou Tiao, Beijing 100069, China.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Capital Medical University, 10 You An Men Wai Xi Tou Tiao, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007473:Ion Channels; D039823:Iridoids / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D024101:Mitochondrial Proteins; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000473:pathology; D019308:Palmitic Acid / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D039823:Iridoids; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D019308:Palmitic Acid; C007834:genipin; D053148:Caspase 3