文献类型：期刊文献

英文题名：Hexavalent chromium induces hepatocyte apoptosis via regulation of apoptosis signal-regulating kinase 1/c-Jun amino-terminal kinase signaling

作者：Jin, Lifang[1];Kom, Merveille Chancelle[1];Fu, Guoquan[1];Xie, Yixia[1];Gao, Yue[1];Shen, Jiayuan[1,2];Huang, Huarong[3];Hu, Baowei[1];Yan, Junyan[1]

机构：[1]Shaoxing Univ, Sch Life Sci, Shaoxing 312000, Zhejiang, Peoples R China;[2]Shaoxing Univ, Affiliated Hosp, Dept Pathol, Shaoxing, Zhejiang, Peoples R China;[3]Hangzhou Normal Univ, Coll Life & Environm Sci, Hangzhou, Peoples R China

年份：2022

卷号：37

期号：6

起止页码：1288

外文期刊名：ENVIRONMENTAL TOXICOLOGY

收录：SCI-EXPANDED(收录号：WOS:000755098900001)、、EI(收录号：20220711646687)、Scopus(收录号：2-s2.0-85124611199)、WOS

基金：Natural Science Foundation of Zhejiang Province

语种：英文

外文关键词：ASK1; GS-444217; hepatocytes; hexavalent chromium [Cr(VI)]; JNK

外文摘要：With the spread of hexavalent chromium (Cr(VI)) contamination, Cr(VI)-induced hepatotoxicity has attracted increasing attention in recent years. To date, however, the exact mechanism of Cr(VI) toxicity remains unclear. In this study, we investigated the role of apoptosis signal-regulating kinase 1 (ASK1)/c-Jun amino-terminal kinase (JNK) in Cr(VI)-induced hepatic toxicity and the possible related mechanisms. AML-12 hepatocyte cell-lines were treated with 0, 1, 4, and 16 mu mol/Lof Cr(VI) with or without GS-444271 (an ASK1 inhibitor). Adult male mice were administered with 0, 2, 8, and 32 mg/kg body mass (BM)/day of Cr(VI) for 5 days. The level of hepatocyte apoptosis/proliferation, generation of reactive oxygen species (ROS), and expression levels of mRNAs and proteins related to ASK1/JNK and nuclear factor-E2-related factor 2 (Nrf2) signaling were assessed. Results showed that high Cr(VI) exposure induced hepatocyte apoptosis and liver injury by generation of ROS and down-regulation of Nrf2 signaling. In addition, ASK1/JNK signaling activity was upregulated in the Cr(VI)-treated group. Furthermore, GS-444217 treatment significantly rescued Cr(VI)-induced hepatocyte apoptosis and liver dysfunction in vitro and in vivo by down-regulation of ASK1/JNK signaling. Thus, ASK1/JNK signaling appears to play an important role in Cr(VI)-induced hepatocyte apoptosis and liver injury. This study should help improve our understanding of the mechanism of Cr(VI)-induced liver injury and provide support for future investigations on liver disease therapy.