1. Cadmium induced mouse spermatogonia apoptosis via mitochondrial calcium overload mediated by IP3R-MCU signal pathway.
- Author
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Liu, Hao, Wang, Rong, OuYang, Huijuan, Wang, Yi, Wu, Jie, Li, Mengyuan, Hu, Yuan, Yao, Yuyou, Liu, Yehao, and Ji, Yanli
- Subjects
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MITOCHONDRIA , *CELLULAR signal transduction , *CADMIUM , *HEAVY metals , *GERM cells , *CHELATING agents - Abstract
Cadmium (Cd) is a toxic metal and also a well-known reproductive toxicant. Cd could induce germ cells apoptosis in mouse testes, however, the mechanism remains unclear. This study designed in vitro using GC-1 spermatogonial (spg) cells to explore the cytotoxicity and the molecular mechanisms induced by cadmium chloride(CdCl 2). As expected, CdCl 2 elevated the levels of reactive oxygen species (ROS) and induced the release of AIF and Cyt-c from the mitochondria to the cytosol in spermatogonia. Correspondingly, CdCl 2 apparently increased the apoptotic rate in spermatogonia. Further researches found that CdCl 2 could activate IP 3 R-MCU pathway, trigger Ca2+ transfer from endoplasmic reticulum to mitochondria, and cause mitochondrial Ca2+ overload. BAPTA acetoxymethyl ester (BAPTA-AM), a calcium chelator, almost completely attenuated IP 3 R phosphorylation, inhibited the mRNA and protein expression levels of VDAC1, MCU and MCUR1 upregulated by CdCl 2 , reduced the calcium ion content in the mitochondria. Moreover, BAPTA-AM could decrease the level of ROS, antagonize CdCl 2 -induced release of AIF and Cyt-c from the mitochondria to the cytosol and alleviate CdCl 2 -induced apoptosis in spermatogonia. As above, these results provided the evidence that CdCl 2 might induce apoptosis of spermatogonia via mitochondrial Ca2+ overload mediated by IP 3 R-MCU signal pathway. • Cd induced spermatogonia apoptosis. • Cd caused mitochondrial Ca2+ overload. • Cd activated IP 3 R-MCU calcium regulation axis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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