The role of PGC-1α and MRP1 in lead-induced mitochondrial toxicity in testicular Sertoli cells

Zhen Li, Xi Liu, Lu Wang, Yan Wang, Chuang Du, Siyuan Xu, Yucheng Zhang, Chunhong Wang, Chengfeng Yang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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-γ coactivator 1α (PGC-1α) 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-1α, but increased the level of MRP1 in mitochondria of TM4 cells. To determine the role of PGC-1α and MRP1 in lead acetate-induced mitochondrial toxicity, we then generated PGC-1α 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-1α 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-1α and MRP1 plays important roles in protecting TM4 cells against lead-induced mitochondrial toxicity, providing a better understanding of lead-induced mitochondrial toxicity.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalToxicology
Volume355-356
DOIs
StatePublished - Apr 29 2016

Bibliographical note

Funding Information:
The authors thank all members in Professor CH. Wang’s laboratory in Wuhan University for their valuable assistances and Dr. Weihuang Liu from the School of Basic Medical Sciences of Wuhan University for her technical assistance with the flow cytometry. This work was supported by the National Natural Science Foundation of China (grant number 81172628 ) and the Fundamental Research Funds for the Central Universities (grant number 2014305020201 ) and the Open Fund of Hubei Provincial Key Laboratory for Applied Toxicology , Hubei Provincial Academy for Preventive Medicine (grant number 20140002 ).

Publisher Copyright:
© 2016 Elsevier Ireland Ltd.

Keywords

  • Lead acetate
  • MRP1
  • Mitochondrial toxicity
  • PGC-1α
  • Sertoli cell

ASJC Scopus subject areas

  • Toxicology

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