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Arsenic Induces Thioredoxin 1 and Apoptosis in Human Liver HHL-5 Cells

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Abstract

To further characterize the mechanisms underlying liver toxicity induced by arsenic, we examined in this study the effect of arsenic on thioredoxin (Trx) and the apoptotic signaling pathways in human liver HHL-5 cells. The cells were treated with 0, 2, 5, and 10 μM of sodium arsenite for 24 h, and the changes of Trx1 and thioredoxin reductase (TrxR1) as well as intracellular ROS and apoptosis were examined. A concentration-dependent increase in mRNA and protein levels of Trx1 and TrxR1 was observed in arsenic-treated cells. Intracellular ROS levels and apoptosis were also significantly increased in a concentration-dependent manner. In line with this, protein levels of Bax and cytochrome C were increased and Bcl-2 was decreased by arsenic treatments. Increases in caspase 3 activity were observed. These results indicate that Trx is involved in arsenic-induced liver cell injury, probably through the apoptotic signaling pathway. However, further studies are needed to elucidate on these findings.

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Acknowledgments

We are grateful to Dr. Arvind Patel (MRC Virology Unit, Glasgow, UK) for providing the immortalized human hepatocytes. This research was supported by the National Natural Science Foundation of China (81502763), China Postdoctoral Research Fund (2013 M541414), and Postdoctoral Fund of Heilongjiang Province (2013LBH-Z13152). We would like to thank Drs. Yanmei Yang, Xiaona Liu, and Xiaoyan Fu in the Central Laboratory of the Center for Endemic Disease Control, Harbin Medical University, for their guidance on the test methods and data analysis.

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Author notes

  1. Xiaohui Cui

    Present address: Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China

  2. Yuanyuan Li and Yuanyuan Zhang contributed equally to this work.

Authors and Affiliations

  1. Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Laboratory of Etiologic Epidemiology of Education Bureau of Heilongjiang Province and Ministry of Health, Harbin Medical University, Harbin, 150081, China

    Yuanyuan Li, Yuanyuan Zhang, Yanhui Gao, Wei Zhang, Xiaohui Cui & Junqiu Liu

  2. Department of Community Medicine, Mercer University School of Medicine, Macon, GA, 31207, USA

    Yudan Wei

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  1. Yuanyuan Li
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  4. Wei Zhang
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Correspondence to Yudan Wei.

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Li, Y., Zhang, Y., Gao, Y. et al. Arsenic Induces Thioredoxin 1 and Apoptosis in Human Liver HHL-5 Cells. Biol Trace Elem Res 181, 234–241 (2018). https://doi.org/10.1007/s12011-017-1052-9

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  • DOI: https://doi.org/10.1007/s12011-017-1052-9

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