期刊
TOXICOLOGY
卷 355, 期 -, 页码 39-48出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2016.05.016
关键词
Lead acetate; Mitochondrial toxicity; Sertoli cell; PGC-1 alpha; MRP1
资金
- National Natural Science Foundation of China [81172628]
- Fundamental Research Funds for the Central Universities [2014305020201]
- Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Academy for Preventive Medicine [20140002]
The lead-induced toxic effect on mitochondria in Sertoli cells is not well studied and the underlying mechanism is poorly understood. Here we reported the potential role of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha) and multidrug resistance protein 1 (MRP1) in lead acetate induced mitochondrial toxicity in mouse testicular Sertoli cells TM4 line. We found that lead acetate treatment significantly reduced the expression level of PGC-1 alpha, but increased the level of MRP1 in mitochondria of TM4 cells. To determine the role of PGC-1 alpha and MRP1 in lead acetate-induced mitochondrial toxicity, we then generated PGC-1 alpha stable overexpression and MRP1 stable knockdown TM4 cells, respectively. The lead acetate treatment caused TM4 cell mitochondrial ultrastructure damages, a decrease in ATP synthesis, an increase in ROS levels, and apoptotic cell death. In contrast, stably overexpressing PGC-1 alpha significantly ameliorated the lead acetate treatment-caused mitochondrial toxicity and apoptosis. Moreover, it was also found that stably knocking down the level of MRP1 increased the TM4 cell mitochondrial lead-accumulation by 4-6 folds. Together, the findings from this study suggest that PGC-1 alpha and MRP1 plays important roles in protecting TM4 cells against lead-induced mitochondrial toxicity, providing a better understanding of lead-induced mitochondria! toxicity. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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