cAMP attenuates angiotensin-II-induced Egr-1 expression via PKA-dependent signaling pathway in vascular smooth muscle cells.
Can J Physiol Pharmacol
; 95(8): 928-937, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-28460186
cAMP has been shown to inhibit vascular smooth muscle cell proliferation and exerts a vasculoprotective effect. An upregulation of the early growth response protein-1 (Egr-1) expression has been linked with the development of atherosclerosis and intimal hyperplasia. We have recently demonstrated that angiotensin-II (Ang-II) stimulates Egr-1 expression via Ca2+/ERK-mediated cAMP-response element binding protein (CREB) activation. However, whether Ang-II-induced signaling leading to Egr-1 expression is modulated by cAMP remains unexplored. Therefore, in the present studies, we have examined the effect of cAMP on Ang-II-induced expression of Egr-1 and associated signaling pathways. Isoproterenol (ISO) and forskolin (FSK) attenuated Ang-II-induced Egr-1 expression in a dose-dependent fashion. In addition, dibutyryl-cAMP and benzoyl-cAMP, as well as isobutylmethylxanthine, attenuated Ang-II-induced Egr-1 expression. Moreover, inhibition of Ang-II-induced Egr-1 expression was accompanied by an increase in the phosphorylation of the vasodilator-activated phosphoprotein (VASP), and this was associated with a concomitant decrease in ERK phosphorylation. Blockade of PKA using H89 decreased VASP phosphorylation, restored Ang-II-induced ERK phosphorylation, and abolished ISO- and FSK-mediated inhibition of Ang-II-induced Egr-1 expression. In summary, these results suggest that PKA-mediated suppression of Ang-II-induced Egr-1 expression and phosphorylation of ERK may be among the mechanisms by which cAMP exerts its vasculoprotective effects.
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 de la Expresión Génica
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Proteínas Quinasas Dependientes de AMP Cíclico
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AMP Cíclico
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Proteína 1 de la Respuesta de Crecimiento Precoz
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Músculo Liso Vascular
Límite:
Animals
Idioma:
En
Revista:
Can J Physiol Pharmacol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Canadá