自噬
细胞生物学
基因敲除
GSTP1公司
破骨细胞
化学
PI3K/AKT/mTOR通路
下调和上调
蛋白激酶B
癌症研究
磷酸化
生物
谷胱甘肽
体外
信号转导
细胞凋亡
生物化学
基因
酶
作者
Xiaoxiao Ji,Jianqiao Hong,Weinan Yang,Minjun Yao,Jie Wang,Guangyao Jiang,Yibo Wang,Congsun Li,Jiyan Lin,Haochen Mou,Chaozhong Li,Sihao Li,Yazhou Chen,Minming Shi,Wei Wang,Fei Lu,Haobo Wu,Xiang Zhao,Yiying Qi,Shigui Yan
出处
期刊:Redox biology
[Elsevier]
日期:2023-05-01
卷期号:61: 102635-102635
被引量:2
标识
DOI:10.1016/j.redox.2023.102635
摘要
Glutathione S-transferase P1(GSTP1) is known for its transferase and detoxification activity. Based on disease-phenotype genetic associations, we found that GSTP1 might be associated with bone mineral density through Mendelian randomization analysis. Therefore, this study was performed both in vitro cellular and in vivo mouse model to determine how GSTP1 affects bone homeostasis. In our research, GSTP1 was revealed to upregulate the S-glutathionylation level of Pik3r1 through Cys498 and Cys670, thereby decreasing its phosphorylation, further controlling the alteration of autophagic flux via the Pik3r1-AKT-mTOR axis, and lastly altering osteoclast formation in vitro. In addition, knockdown and overexpression of GSTP1 in vivo also altered bone loss outcomes in the OVX mice model. In general, this study identified a new mechanism by which GSTP1 regulates osteoclastogenesis, and it is evident that the cell fate of osteoclasts is controlled by GSTP1-mediated S-glutathionylation via a redox-autophagy cascade.
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