title: Role of p53 in the cellular response following oleic acid accumulation in Chang liver cells.
abstract: Abnormal accumulation of fatty acids triggers the harmful cellular response called lipotoxicity. In this study, we investigated the cellular response following accumulation of oleic acid (OA), a monounsaturated fatty acid, in human Chang liver cells. OA droplets were distributed freely in the cytoplasm and/or degraded within lysosomes. OA exposure increased ATP production and concomitantly dilated mitochondria. At 24h after OA exposure, cell viability decreased slightly and was coupled with a reduction in mitochondrial Ca(2+) concentration, the alteration in cell viability was also associated with the generation of reactive oxygen species and changes in the cell cycle. Moreover, OA treatment increased the expression of autophagy- and apoptotic cell death-related proteins in a dose-dependent manner. Furthermore, we investigated the role of p53, a tumor suppressor protein, in the cellular response elicited by OA accumulation. OA-induced changes in cell viability and ATP production were rescued to control levels when cells were pretreated with pifithrin-alpha (PTA), a p53 inhibitor. By contrast, the expressions of LC3-II and perilipin, proteins required for lipophagy, were down-regulated by PTA pretreatment. Taken together, our results suggest that p53 plays a key role in the cellular response elicited by OA accumulation in Chang liver cells.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Kyeong-Nam
authors.initials: KN
authors.lastname: Yu
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D019301:Oleic Acid / Q000378:metabolism / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019301:Oleic Acid; D000255:Adenosine Triphosphate
keywords: ATP; Autophagy; Lipophagy; Oleic acid; p53