Lentivirus-mediated RNA Interference Targeting I2PP2A Attenuated Trichloroethylene-induced Cytotoxicity in Human L-02 Liver CeUs
Occupational exposure to trichloroethylene (TCE) could cause severe hepatotoxicity. However, the mechanisms of hepato-toxicity caused by TCE remained poorly understood. We have reported by proteomic study that TCE up-regulated the expression of the inhibitor 2 of protein phosphatase 2A (I2PP2A) in human L-02 liver cells. In order to further determine the potential role of I2PP2A in TCE-induced toxicity, we used the techniques of siRNA, Westem-blot analysis, protein phosphatase activity and apoptosis assay to explore whether I2PP2A is involved in TCEinduced cytotoxicity in L-02 liver cells. First, we constructed L-02 cells stably expressing shRNA against I2PP2A by using lentivirus transfection, and found that the activity of PP2A in the stable I2PP2A siRNA L-02 cells was increased by approximately 20% compared to the control cells. We treated the L-02 cells and the stable I2PP2A siRNA L-02 cells with 2. 0mol/L for 24h and found that increased apoptosis caused by TCE were partially attenuated in the stable I2PP2A siRNA L-02 cells. The inhibition of PP2A activity as well as increased activity of casapse-3 induced by TCE in L-02 cells was both partially reversed in the stable I2PP2A siRNA L-02 cells. These data for the first time demonstrated that upregulation of I2PP2A could mediate, at least in part, TCE-induced hepatotoxicity through inhibition of PP2A activity and caspase-3-mediated pathway, and suggested that I2PP2A could be a crucial molecule leading to TCE hepatotoxicity.
Xifei YANG Wenxu HONG Desheng WU Xinfeng HUANG Zhixiong ZHUANG
Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
国际会议
天津
英文
146-148
2011-09-20（万方平台首次上网日期，不代表论文的发表时间）