科研之友
微信
新浪微博
Facebook
分享链接
摘要
Aims: While etiology behind the observed acceleration of ischemic heart disease in postmenopausal women is poorly understood, collective scientific data suggest cardioprotective effects of the endogenous female sex hormone, estrogen. We have previously shown that 17 beta-estradiol (E2) protects cardiomyocytes exposed to hypoxia-reoxygenation (H/R) by inhibiting p38 alpha - p53 signaling in apoptosis and activating pro-survival p38 beta mitogen activated protein kinase (p38 beta MAPK), leading to suppression of reactive oxygen species (ROS) post H/R. However, little is known about the mechanism behind the antioxidant actions of E2-dependent p38 beta. The aim of this study is to determine whether the cytoprotection by estrogen involves regulation of manganese superoxide dismutase (MnSOD), a major mitochondrial ROS scavenging enzyme, via cardiac p38 beta. Methods and Results: We identified mitochondrial p38 beta by immunocytochemistry and by immunoblotting in mitochondria isolated from neonatal cardiomyocytes of Sprague-Dawley rats. E2 facilitated the mitochondrial localization of the active form of the kinase, phosphorylated p38 beta (p-p38 beta). E2 also reduced the H/R-induced mitochondrial membrane potential decline, augmented the MnSOD activity and suppressed anion superoxide generation, while the dismutase protein expression remained unaltered. Co-immunoprecipitation studies showed physical association between MnSOD and p38 beta. p38 beta phosphorylated MnSOD in an E2-dependent manner in in-vitro kinase assays. Conclusion: This work demonstrates for the first time a mitochondrial pool of active p38 beta and E2-mediated phosphorylation of MnSOD by the kinase. The results shed light on the mechanism behind the cytoprotective actions of E2 in cardiomyocytes under oxidative stress.
- 出版日期2014-1-22
