Lentivirus-mediated silencing of I2PP2A through RNA interference attenuates trichloroethylene-induced cytotoxicity in human hepatic L-02 cells
作者单位：Key Laboratory of Modern Toxicology of ShenzhenMedical Key Laboratory of Health ToxicologyShenzhen Center for Disease Control and Prevention
会议名称：《2012深圳市预防医学会学术研讨会》
会议日期：2012年
学科分类：100405[医学-卫生毒理学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 10[医学]
基 金：supported by the NSFC(the National Natural Science Foundation of China) the Upgrade Scheme of Shenzhen Municipal Key Laboratory[CXB201 005260068A] the Key project of the Shenzhen Science and Technology Plan
关 键 词：12PP2A Protein phosphatase(PP) 2A Trichloroethylene(TCE) siRNA
摘 要：Trichloroethylene(TCE) is a common chemical pollutant that exists in air,soil,and drinking *** exposure is known to cause severe hepatotoxicity,however,the mechanisms underlying TCE hepatotoxicity remain poorly *** a previous proteomics study,we found that TCE exposure up-regulated the expression of the inhibitor 2 of protein phosphatase 2A(12PP2A),a potent and specific endogenous inhibitor of protein phosphatase(PP) 2A,in human hepatic L-02 ***,we employed lentivirusmediated RNA interference(RNAi) to knock down 12PP2A expression in L-02 ceils and explored the potential role of 12PP2A in TCE-induced *** found that TCE treatment of L-02 cells causes decreased cell viability,increased apoptosis and elevated 12PP2A mRNA and protein ***-treated L-02 ceils were also found to have significantly reduced PP2A ***-mediated 12PP2A knockdown partially prevented the decrease in viability and increased apoptosis induced by TCE treatment. Knockdown of 12PP2A in TCE-treated L-02 cells also suppressed the inhibition of PP2A activity and prevented caspase-3 *** data for the first time demonstrate that the up-regulation of 12PP2A 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.