Role of p53 in the cellular response following oleic acid accumulation in Chang liver cells

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• 作者：Eun-Jung Park ; Ah Young Lee ; Seung-Hee Chang ; Kyeong-Nam Yu ; Jae-Ho Kim ; Myung-Haing Cho
• 关键词：Oleic acid ; Autophagy ; p53 ; Lipophagy ; ATP
• 刊名：Toxicology Letters
• 出版年：3 January, 2014
• 年：2014
• 卷：224
• 期：1
• 页码：114-120
• 全文大小：1737 K

文摘

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 24 h after OA exposure, cell viability decreased slightly and was coupled with a reduction in mitochondrial Ca²⁺ 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.