SIRT3 inhibition suppresses hypoxia‐inducible factor 1α signaling and alleviates hypoxia‐induced apoptosis of type B spermatogonia GC‐2 cells
Zixuan Wang,
Chunchun Zhu,
Yangyang Song,
Xiaoyun Chen,
Jie Zheng,
Lian He,
Xing Liu,
Zhu Chen
Affiliations
Zixuan Wang
University of Chinese Academy of Sciences Beijing China
Chunchun Zhu
University of Chinese Academy of Sciences Beijing China
Yangyang Song
Department of Reproduction, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Xiaoyun Chen
University of Chinese Academy of Sciences Beijing China
Jie Zheng
Department of Reproduction, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Lian He
Department of Reproduction, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Xing Liu
University of Chinese Academy of Sciences Beijing China
Zhu Chen
Department of Reproduction, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Hypoxia has been reported to be an important factor leading to male infertility, and it has been reported that hypoxia can induce the apoptosis of mouse spermatogenic cells. Sirtuin 3 (SIRT3) has been reported to promote the degradation of hypoxia‐inducible factor 1α (HIF‐1α), and thus, we hypothesized that SIRT3 may influence hypoxia‐induced apoptosis of spermatogonia. In this study, we overexpressed or inhibited SIRT3 in mouse type B spermatogonia GC‐2 cells and then subjected the cells to hypoxia or normoxia, before examining hypoxia‐responsive gene expression and cell viability. We report that SIRT3 stabilizes hypoxia‐inducible factor 1α (HIF‐1α) and activates its downstream target gene expression in GC‐2 cells. We also show that the SIRT3 inhibitor 3‐TYP suppresses HIF‐1α target gene expression and alleviates hypoxia‐induced apoptosis of GC‐2 cells. Our study reveals the critical role and underlying mechanisms of SIRT3 in hypoxia‐induced apoptosis of mouse type B spermatogonia GC‐2 cells.
