BMI1 promotes steroidogenesis through maintaining redox homeostasis in mouse MLTC-1 and primary Leydig cells. Issue 15 (2nd August 2020)

• Record Type: Journal Article
• Authors: Gao, Tingting; Lin, Meng; Shao, Binbin; Zhou, Qiao; Wang, Yufeng; Chen, Xia; Zhao, Dan; Dai, Xiuliang; Shen, Cong; Cheng, Hongbo; Yang, Shenmin; Li, Hong; Zheng, Bo; Zhong, Xingming; Yu, Jun; Chen, Li; Huang, Xiaoyan
• Is Part Of: Cell cycle. Volume 19:Issue 15(2020)
• Page Start: 1884
• Page End: 1898
• Publication Date: 2020-08-02
• Subjects: Leydig cells -- BMI1 -- oxidative stress -- p16/p19 signaling -- steroidogenesis; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2020.1779471
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: In males, aging is accompanied by decline in serum testosterone levels due to impairment of testicular Leydig cells. The polycomb protein BMI1 has recently been identified as an anti-aging factor. In our previous study, BMI1 null mice showed decreased serum testosterone and Leydig cell population, excessive oxidative stress and p16/p19 signaling activation. However, a cause-and-effect relationship between phenotypes and pathways was not investigated. Here, we used the rescue approach to study the role of oxidative stress or p16/p19 in BMI1-mediated steroidogenesis. Our results revealed that treatment with antioxidant NAC, but not down-regulation of p16/p19, largely rescued cell senescence, DNA damage and steroidogenesis in BMI1-deficient mouse MLTC-1 and primary Leydig cells. Collectively, our study demonstrates that BMI1 orchestrates steroidogenesis mainly through maintaining redox homeostasis, and thus, BMI1 may be a novel and potential therapeutic target for treatment of hypogonadism.