Exploring the effects of tert-butylhydroperoxide induced liver injury using proteomic approach

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• 作者：Chien-Heng Shen ; Shui-Yi Tung ; Wen-Shih Huang ; Chien-Chang Lu ; Ko-Chao Lee ; Yung-Yu Hsieh ; Pey-Jium Chang ; Hwey-Fang Liang ; Jiann-Hwa Chen ; Tseng-Hsi Lin ; Meng Chiao Hsieh ; Hsing-Chun Kuo
• 关键词：t-BHP ; ETFA ; ROS ; IRE1-alpha/TRAF2 ; JNK1/2 ; NF魏B
• 刊名：Toxicology
• 出版年：28 February, 2014
• 年：2014
• 卷：316
• 期：Complete
• 页码：61-70
• 全文大小：2989 K

文摘

Tert-butyl hydroperoxide (t-BHP), an organic lipid hydroperoxide analog, has been demonstrated to exert pro-oxidant effects to evaluate mechanisms involving oxidative stress in hepatocyte cells and rat liver. Herein, we present an investigation of the event of molecular mechanism of t-BHP related acute liver injury. A proteomic approach was used to identify proteins which are differentially expressed in liver cells following t-BHP treatment and the mechanism of its action in apoptotic and endoplasmic reticulum stress pathways. Our results demonstrate that the t-BHP treatment of liver cells increased cell cytoxicity and apoptosis. t-BHP dose-dependent induction of cell apoptosis and stained liver sections relieved the acute rat liver injury were accompanied by sustained phosphorylation of JNK1/2 and p65. In addition, there were 13 differentially displayed proteins between the t-BHP-induced and untreated were assayed and validated in vivo. Furthermore, we demonstrated that t-BHP induced human Chang liver cell viability and apoptosis properties by up-regulating the levels of ETFA (electron transfer flavoprotein subunit alpha). This study demonstrated that there was an increase in the cellular levels of ETFA in the t-BHP induction in viability and apoptosis via the activation of JNK1/2 and NF魏B signaling modules. NAC administration and shRNA ETFA conferred resistance to t-BHP-increased ETFA and CHOP expression via IRE1-alpha/TRAF2 complex formation, activation of JNK1/2 and p50. We concluded that the mechanism of t-BHP-induced an apoptosis cascade and endoplasmic reticulum stress in hepatocyte cells by up-regulation of ETFA, providing a new mechanism for liver injury.