Effects of regulator of G protein signaling 19 (RGS19) on heart development and function.
J Biol Chem
; 285(37): 28627-34, 2010 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-20562099
ABSTRACT
Wnt/Wg genes play a critical role in the development of various organisms. For example, the Wnt/beta-catenin signal promotes heart formation and cardiomyocyte differentiation in mice. Previous studies have shown that RGS19 (regulator of G protein signaling 19), which has Galpha subunits with GTPase activity, inhibits the Wnt/beta-catenin signal through inactivation of Galpha(o). In the present study, the effects of RGS19 on mouse cardiac development were observed. In P19 teratocarcinoma cells with RGS19 overexpression, RGS19 inhibited cardiomyocyte differentiation by blocking the Wnt signal. Additionally, several genes targeted by Wnt were down-regulated. For the in vivo study, we generated RGS19-overexpressing transgenic (RGS19 TG) mice. In these transgenic mice, septal defects and thin-walled ventricles were observed during the embryonic phase of development, and the expression of cardiogenesis-related genes, BMP4 and Mef2C, was reduced significantly. RGS19 TG mice showed increased expression levels of brain natriuretic peptide and beta-MHC, which are markers of heart failure, increase of cell proliferation, and electrocardiogram analysis shows abnormal ventricle repolarization. These data provide in vitro and in vivo evidence that RGS19 influenced cardiac development and had negative effects on heart function.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Diferenciación Celular
/
Proteínas RGS
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Miocitos Cardíacos
/
Corazón
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2010
Tipo del documento:
Article