title: Cardioprotection of 17β-estradiol against hypoxia/reoxygenation in cardiomyocytes is partly through up-regulation of CRH receptor type 2.
abstract: 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 17β-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 α (ERα) antagonist treatment or ERα 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 ERα agonist treatment. These results suggest that estrogens act on ERα to up-regulate CRHR2 expression in cardiomyocytes, thereby enhancing cardioprotection of UCNs against H/R.
authors.affiliation: Department of Physiology, The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China.
authors.forename: Binhai
authors.initials: B
authors.lastname: Cong
authors.affiliation: Department of Physiology, The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Physiology, The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Physiology, The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Physiology, The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Physiology, The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Tang
authors.affiliation: School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Physiology, The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China. Electronic address: nixinsmmu@hotmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D054832:Urocortins / Q000494:pharmacology
chemical_list: C101531:CRF receptor type 2; D002316:Cardiotonic Agents; D047628:Estrogen Receptor alpha; D018019:Receptors, Corticotropin-Releasing Hormone; D016329:Sp1 Transcription Factor; D054832:Urocortins; D004958:Estradiol; D010100:Oxygen
keywords: 17β-estradiol; CRHR2; Cardiomyocytes; Corticotropin-releasing hormone receptor type 2; E2; ER; EREs; Estrogens; H/R; Hypoxia/reoxygenation; IHD; IPC; LDH; Lactate Dehydrogenase; MTT; RIA; Radioimmunoassay; Sp1; Specific protein1; UCN; Urocortins; corticotrophin-releasing hormone receptor type 2; estrogen receptor; estrogen responses elements; hypoxia/reoxygenation; ischemic heart disease; ischemic preconditioning; methyl thiazolyl tetrazolium; siRNA; small interfering RNA; specific protein 1; urocortin