标题：The orphan nuclear receptor NR4A1 attenuates oxidative stress-induced beta cells apoptosis via up-regulation of glutathione peroxidase 1
作者：Yang, Yingfeng; Xie, Fangyu; Qin, Dandan; Zong, Chen; Han, Feng; Pu, Zeqing; Liu, Dong; Li, Xia; Zhang, Yuchao; Liu, Yuantao; Wang 更多 作者机构：[Yang, Yingfeng; Qin, Dandan; Zong, Chen; Pu, Zeqing; Liu, Dong; Li, Xia; Wang, Xiangdong] Shandong Univ, Dept Cell Biol, Sch Med, Jinan 250012, Shand 更多
通讯作者地址：[Wang, XD]Shandong Univ, Dept Cell Biol, Sch Med, Jinan 250012, Shandong, Peoples R China.
关键词：GPX1; NR4A1; Oxidative stress
摘要：Aims: Our previous study showed that NR4A1 protects against oxidative stress-induced cell apoptosis. However, the targets downstream of NR4A1 are incompletely known. Glutathione peroxidase 1 ( GPX1) is the most common antioxidant enzyme in the glutathione peroxidase class. In this study, we aimed to investigate whether GPX1 is a mediator of the protective effects of NR4A1 in pancreatic beta cells.; Main methods: A pancreatic beta cell line, MIN6, was used to generate NR4A1 over-expression cell line. GPX1 expression and GPX1 promoter trans-activation in these cells was determined. These cells were then treated with H2O2, and the active caspase3 level was determined.; Key findings: NR4A1 over-expression in MIN6 cells resulted in increased GPX1 expression at both mRNA and protein levels. Dual luciferase assay showed that NR4A1 over-expression was able to enhance the trans-activation of GPX1 promoter, and the critical regulatory elements were narrowed down between 0 to -2000 bp in GPX1 promoter with a putative NR4A1 binding site (-273 to -268). ChIP assays demonstrated that NR4A1 physically associates with the GPX1 promoter. Over-expression of GPX1 reduced the active level of Caspase3 after H2O2 treatment.; Significance: NR4A1 increases the expression of GPX1 by enhancing the trans-activation of GPX1 promoter through binding to the putative binding site on GPX1 promoter. NR4A1 potentially protects pancreatic beta cells against oxidative stress-induced apoptosis by increasing GPX1 expression.