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cAMP attenuates angiotensin-II-induced Egr-1 expression via PKA-dependent signaling pathway in vascular smooth muscle cells.
Simo-Cheyou, Estelle R; Youreva, Viktoria; Srivastava, Ashok K.
Afiliación
  • Simo-Cheyou ER; a Laboratory of Cellular Signaling, Montreal Diabetes Research Center and Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900 Rue St-Denis, Montreal, QC H2X 0A9, Canada.
  • Youreva V; b Department of Nutrition, Faculty of Medicine, University of Montreal, C.P. 6128, Succursale centre-ville, Montreal, QC H3C 3J7, Canada.
  • Srivastava AK; a Laboratory of Cellular Signaling, Montreal Diabetes Research Center and Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900 Rue St-Denis, Montreal, QC H2X 0A9, Canada.
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Angiotensina II / Transducción de Señal / Regulación de la Expresión Génica / Proteínas Quinasas Dependientes de AMP Cíclico / AMP Cíclico / Proteína 1 de la Respuesta de Crecimiento Precoz / 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

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Angiotensina II / Transducción de Señal / Regulación de la Expresión Génica / Proteínas Quinasas Dependientes de AMP Cíclico / AMP Cíclico / Proteína 1 de la Respuesta de Crecimiento Precoz / 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