Cardioprotection of 17尾-estradiol against hypoxia/reoxygenation in cardiomyocytes is partly through up-regulation of CRH receptor type 2

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• 作者：Binhai Cong ; Yongjun Xu ; Hui Sheng ; Xiaoyan Zhu ; Long Wang ; Wei Zhao ; Zhiping Tang ; Jianqiang Lu ; Xin Ni
• 关键词：CRHR2 ; corticotrophin-releasing hormone receptor type 2 ; E2 ; 17尾-estradiol ; ER ; estrogen receptor ; EREs ; estrogen responses elements ; H/R ; hypoxia/reoxygenation ; IHD ; ischemic heart disease ; IPC ; ischemic preconditioning ; LDH ; Lactate Dehydrogenase ; MTT ; methyl thiazolyl tetrazolium ; RIA ; Radioimmunoassay ; siRNA ; small interfering RNA ; Sp1 ; specific protein 1 ; UCN ; urocortin
• 刊名：Molecular and Cellular Endocrinology
• 出版年：25 January, 2014
• 年：2014
• 卷：382
• 期：1
• 页码：17-25
• 全文大小：1866 K

文摘

Estrogens have been suggested to exert cardioprotection through maintaining endogenous cardioprotective mechanisms. In the present study, we investigated whether estrogens protect cardiomyocytes against hypoxia/reoxygenation (H/R) via modulating urocortins (UCNs) and their receptor corticotrophin-releasing hormone receptor type 2 (CRHR2). We found that 17尾-estradiol (E2) enhanced UCN cardioprotection against H/R and increased CRHR2 expression in neonatal rat cardiomyocytes. E2 protected cardiomyocytes against H/R, which was impaired by CRHR2 antagonist or knockdown of CRHR2. Estrogen receptor 伪 (ER伪) antagonist treatment or ER伪 knockdown could abolish E2-induced CRHR2 up-regulation. Moreover, knockdown of Sp1 also attenuated E2-induced CRHR2 up-regulation. Ovariectomy resulted in down-regulation of CRHR2 and Sp-1 in myocardium of mice, which was restored by E2 or ER伪 agonist treatment. These results suggest that estrogens act on ER伪 to up-regulate CRHR2 expression in cardiomyocytes, thereby enhancing cardioprotection of UCNs against H/R.