Perfluorooctanoic acid induces apoptosis through the p53-dependent mitochondrial pathway in human hepatic cells: A proteomic study
Perfluorooctanoic acid induces apoptosis through the p53-dependent mitochondrial pathway in human hepatic cells: A proteomic study
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全氟辛酸通过 p53 依赖性线粒体途径诱导人肝细胞凋亡：一项蛋白质组学研究
DOI：
10.1016/j.toxlet.2013.09.002
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发表时间：
2013-11-25
影响因子：
3.5
通讯作者：
Shen, Heqing
中科院分区：
文献类型：
--
作者：
Huang, Qingyu;Zhang, Jie;Shen, Heqing
全氟辛酸（PFOA）是最常用的全氟化合物之一，接触它会对健康产生许多不利影响。然而，涉及PFOA毒性的分子机制仍然没有得到很好的表征。在本研究中，流式细胞仪分析显示，PFOA诱导氧化应激，细胞周期阻滞和凋亡的人非肿瘤肝细胞（L-02）。此外，我们还研究了PFOA对L-02细胞蛋白质组的影响，旨在从蛋白质组水平探讨PFOA肝毒性的机制。在28个对PFOA有显著差异表达的蛋白质中，24个下调，4个上调。蛋白质组学研究表明，GRP 78、HSP 27、CTSD和hnRNPC等蛋白质的抑制可能参与了p53的激活，从而导致L-02细胞凋亡。通过p53依赖性线粒体途径诱导细胞凋亡进一步表明是PFOA胁迫下L-02细胞中发生的关键毒理学事件之一。我们希望这些数据将揭示PFOA介导的人类肝细胞毒性的分子机制，并从这些研究中可以开发出指示PFOA暴露的有用生物标志物。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated compounds, and exposure to it has been associated with a number of adverse health effects. However, the molecular mechanisms involved in PFOA toxicity are still not well characterized. In the present study, flow cytometry analysis revealed that PFOA induced oxidative stress, cell cycle arrest and apoptosis in human non-tumor hepatic cells (L-02). Furthermore, we investigated the alterations in protein profile within L-02 cells exposed to PFOA, aiming to explore the mechanisms underlying PFOA hepatotoxicity on the proteome level. Of the 28 proteins showing significant differential expression in response to PFOA, 24 were down-regulated and 4 were up-regulated. This proteomic study proposed that the inhibition of some proteins, including GRP78, HSP27, CTSD and hnRNPC may be involved in the activation of p53, which consequently triggered the apoptotic process in L-02 cells. Induction of apoptosis via the p53-dependent mitochondrial pathway is further suggested as one of the key toxicological events occurring in L-02 cells under PFOA stress. We hope these data will shed new light on the molecular mechanisms responsible for PFOA-mediated toxicity in human liver cells, and from such studies useful biomarkers indicative of PFOA exposure could be developed. (C) 2013 Elsevier Ireland Ltd. All rights reserved.