Short-term hypoxia upregulated Mas receptor expression to repress the AT1 R signaling pathway and attenuate Ang II-induced cardiomyocyte apoptosis.
J Cell Biochem
; 119(3): 2742-2749, 2018 03.
Article
en En
| MEDLINE
| ID: mdl-29052864
ABSTRACT
Hypertension-stimulated cardiac hypertrophy and apoptosis play critical roles in the progression of heart failure. Our previous study suggested that hypertensive angiotensin II (Ang II) enhanced insulin-like growth factor receptor II (IGF-IIR) expression and cardiomyocyte apoptosis, which are involved JNK activation, sirtuin1 (SIRT1) degradation, and heat-shock transcription factor 1 (HSF1) acetylation. Moreover, previous studies have implied that short-term hypoxia (STH) might exert cardioprotective effects. However, the effects of STH on Ang II-induced cardiomyocyte apoptosis remain unknown. In this study, we found that STH reduced myocardial apoptosis caused by Ang II via upregulation of the Mas receptor (MasR) to inhibit the AT1 R signaling pathway. STH activates MasR to counteract the Ang II pro-apoptotic signaling cascade by inhibiting IGF-IIR expression via downregulation of JNK activation and reduction of SIRT1 degradation. Hence, HSF could remain deacetylated, and repress IGF-IIR expression. These effects decrease the activation of downstream pro-apoptotic and hypertrophic cascades and protect cardiomyocytes from Ang II-induced injury. In addition, we also found that silencing MasR expression enhanced Ang II-induced cardiac hypertrophy and the apoptosis signaling pathway. These findings suggest a critical role for MasR in cardiomyocyte survival. Altogether, our findings indicate that STH protects cardiomyocytes from Ang II-stimulated apoptosis. The protective effects of STH are associated with the upregulation of MasR to inhibit AT1 R signaling. STH could be a potential therapeutic strategy for cardiac diseases in hypertensive patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Angiotensina II
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Transducción de Señal
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Regulación hacia Arriba
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Proteínas Proto-Oncogénicas
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Apoptosis
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Miocitos Cardíacos
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Receptores Acoplados a Proteínas G
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Receptor de Angiotensina Tipo 1
Límite:
Animals
Idioma:
En
Revista:
J Cell Biochem
Año:
2018
Tipo del documento:
Article
País de afiliación:
Taiwán