17ß-Estradiol and/or Estrogen Receptor ß Attenuate the Autophagic and Apoptotic Effects Induced by Prolonged Hypoxia Through HIF-1α-Mediated BNIP3 and IGFBP-3 Signaling Blockage.
Cell Physiol Biochem
; 36(1): 274-84, 2015.
Article
em En
| MEDLINE
| ID: mdl-25967966
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 17ß-estradiol (E2) prevents cardiomyocyte hypertrophy, autophagy and apoptosis via estrogen receptor α (ERα), but the effects of ERß on myocardial injury remained elusive. The present paper thus, investigated the cardioprotective effects of estrogen (E2) and ERß against hypoxia-induced cell death.METHODS:
Transient transfection of Tet-On ERß gene construct was used to overexpress ERß in hypoxia-treated H9c2 cardiomyoblast cells.RESULTS:
Our data revealed that IGF1R, Akt phosphorylation and Bcl-2 expression are enhanced by ERß in H9c2 cells. Moreover, ERß 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 ERß could totally abolish hypoxia-induced apoptosis. The suppressive effects of E2 and/or ERß in hypoxia-treated NRVMs were totally reversed by ER antagonist, ICI. Taken together, E2 and/or ERß 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/ERß treatment could be a potential therapy to prevent hypoxia-induced heart damage."
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Miócitos Cardíacos
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Receptor beta de Estrogênio
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Estradiol
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Subunidade alfa do Fator 1 Induzível por Hipóxia
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article