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PGC-1α对睾丸支持细胞中铅诱导的氧化应激和能量代谢功能障碍的保护作用

Protective Effects of PGC-1α Against Lead-Induced Oxidative Stress and Energy Metabolism Dysfunction in Testis Sertoli Cells.

作者信息

Liu Xi, Ye Jingping, Wang Lu, Li Zhen, Zhang Yucheng, Sun Jiantao, Du Chuang, Wang Chunhong, Xu Siyuan

机构信息

Department of Toxicology, School of Public Health, Wuhan University, DongHu Road 115, Wuhan, 430071, People's Republic of China.

Renmin hospital of Wuhan University, Wuhan, 430060, People's Republic of China.

出版信息

Biol Trace Elem Res. 2017 Feb;175(2):440-448. doi: 10.1007/s12011-016-0799-8. Epub 2016 Jul 9.

Abstract

The reproductive system is sensitive to lead (Pb) toxicity, which has long been an area of research interest, but the underlying mechanisms remain to be illustrated. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is pivotal in mitochondrial function. In this study, mouse testis Sertoli cells (TM4 cells), PGC-1α lower-expression (PGC-1α(-)) TM4 cells and PGC-1α overexpression (PGC-1α(+)) TM4 cells were used to explore the protective roles of PGC-1α against lead toxicity on the mouse reproductive system. Lead acetate (PbAc) exposure decreased the expression level of PGC-1α, increased the intracellular level of reactive oxygen species (ROS), and reduced the level of ATP in the three TM4 cell lines. The effects of PbAc on intracellular ATP level and on ROS content were significantly weakened in PGC-1α(+)TM4 cells versus TM4 cells and were significantly amplified in PGC-1α(-)TM4 cells versus TM4 cells. These results suggest that PGC-1α is a protective factor against PbAc-induced oxidative stress and energy metabolism dysfunction in the mouse reproductive system, thereby holding the potential of being developed as a preventive or therapeutic strategy against disorders induced by lead exposure.

摘要

生殖系统对铅(Pb)毒性敏感,长期以来一直是研究热点领域,但潜在机制仍有待阐明。过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)在线粒体功能中起关键作用。在本研究中,使用小鼠睾丸支持细胞(TM4细胞)、PGC-1α低表达(PGC-1α(-))TM4细胞和PGC-1α过表达(PGC-1α(+))TM4细胞,以探究PGC-1α对铅毒性对小鼠生殖系统的保护作用。醋酸铅(PbAc)暴露降低了PGC-1α的表达水平,增加了三种TM4细胞系中的细胞内活性氧(ROS)水平,并降低了ATP水平。与TM4细胞相比,PbAc对PGC-1α(+)TM4细胞内ATP水平和ROS含量的影响显著减弱,而与TM4细胞相比,在PGC-1α(-)TM4细胞中显著增强。这些结果表明,PGC-1α是小鼠生殖系统中对抗PbAc诱导的氧化应激和能量代谢功能障碍的保护因子,因此具有开发成为针对铅暴露诱导疾病的预防或治疗策略的潜力。

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