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Title: | 17β-Estradiol and/or Estrogen Receptor β Attenuate the Autophagic and Apoptotic Effects Induced by Prolonged Hypoxia Through HIF-1α-Mediated BNIP3 and IGFBP-3 Signaling Blockage |
Authors: | Hsieh, D.J.-Y;Kuo, W.-W;Lai, Y.-P;Shibu, M.A;Shen, C.-Y;Pai, Pai P;Yeh, Yeh Y.-L;Lin, J.-Y;Viswanadha, Viswanadha V.P;Huang, C.-Y |
Contributors: | 中山醫大 |
Keywords: | 17β-estradiolEstrogen receptor βHypoxiaAutophagyCardiac apoptosis |
Date: | 2015 |
Issue Date: | 2017-06-30T09:51:29Z (UTC)
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Publisher: | Cell Physiol Biochem |
ISSN: | 1015-8987 |
Abstract: | Abstract
BACKGROUND/AIMS:
The risk of heart disease is higher in males than in females. However, this advantage of females declines with increasing age, presumably a consequence of decreased estrogen secretion and malfunctioning of the estrogen receptor. We previously demonstrated that 17β-estradiol (E2) prevents cardiomyocyte hypertrophy, autophagy and apoptosis via estrogen receptor α (ERα), but the effects of ERβ on myocardial injury remained elusive. The present paper thus, investigated the cardioprotective effects of estrogen (E2) and ERβ against hypoxia-induced cell death.
METHODS:
Transient transfection of Tet-On ERβ gene construct was used to overexpress ERβ in hypoxia-treated H9c2 cardiomyoblast cells.
RESULTS:
Our data revealed that IGF1R, Akt phosphorylation and Bcl-2 expression are enhanced by ERβ in H9c2 cells. Moreover, ERβ overexpression reduced accumulation of hypoxia-related proteins, autophagy-related proteins and mitochondria-apoptotic proteins and enhanced the protein levels of Bcl-2, pAkt and Bad under hypoxic condition. In neonatal rat ventricular myocytes (NRVMs), we observed that hypoxia induced cell apoptosis as measured by TUNEL staining, and E2 and/or ERβ could totally abolish hypoxia-induced apoptosis. The suppressive effects of E2 and/or ERβ in hypoxia-treated NRVMs were totally reversed by ER antagonist, ICI. Taken together, E2 and/or ERβ exert the protective effect through repressed hypoxia-inducible HIF-1α, BNIP3 and IGFBP-3 levels to restrain the hypoxia-induced autophagy and apoptosis effects in H9c2 cardiomyoblast cells.
CONCLUSION:
The results suggest that females probably could tolerate better prolonged hypoxia condition than males, and E2/ERβ treatment could be a potential therapy to prevent hypoxia-induced heart damage." |
URI: | http://dx.doi.org/10.1159/000374070 https://ir.csmu.edu.tw:8080/ir/handle/310902500/17906 |
Relation: | Cell Physiol Biochem 2015;36:274-284 |
Appears in Collections: | [醫學系] 期刊論文
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