| Lentivirus-mediated silencing of I2PP2A through RNA interference attenuates trichloroethylene-induced cytotoxicity in human hepatic L-02 cells. | |
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MedLine Citation:
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PMID: 22245669 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Trichloroethylene (TCE) is a common chemical pollutant that exists in air, soil, and drinking water. TCE exposure is known to cause severe hepatotoxicity; however, the mechanisms underlying TCE hepatotoxicity remain poorly understood. In a previous proteomics study, we found that TCE exposure up-regulated the expression of the inhibitor 2 of protein phosphatase 2A (I2PP2A), a potent and specific endogenous inhibitor of protein phosphatase (PP) 2A, in human hepatic L-02 cells. Here, we employed lentivirus-mediated RNA interference (RNAi) to knock down I2PP2A expression in L-02 cells and explored the potential role of I2PP2A in TCE-induced cytotoxicity. We found that TCE treatment of L-02 cells causes decreased cell viability, increased apoptosis and elevated I2PP2A mRNA and protein levels. TCE-treated L-02 cells were also found to have significantly reduced PP2A activity. Lentivirus-mediated I2PP2A knockdown partially prevented the decrease in viability and increased apoptosis induced by TCE treatment. Knockdown of I2PP2A in TCE-treated L-02 cells also suppressed the inhibition of PP2A activity and prevented caspase-3 activation. These data for the first time demonstrate that the up-regulation of I2PP2A could mediate, at least in part, TCE-induced liver cell toxicity through the inhibition of PP2A activity and caspase-3-mediated pathway, and suggest that I2PP2A may play a crucial role in mediating TCE hepatotoxicity. |
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Authors:
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Xifei Yang; Yingzhi Jiang; Jie Li; Wen-Xu Hong; Desheng Wu; Xinfeng Huang; Haiyan Huang; Li Zhou; Lingqing Yang; Jianhui Yuan; Zhixiong Zhuang; Jianjun Liu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-8 |
Journal Detail:
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Title: Toxicology letters Volume: - ISSN: 1879-3169 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Ireland Ltd. |
Affiliation:
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Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Health Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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