Roles of ERKs and intracellular free calcium in cardiomyocyte hypertrophic response induced by endothelin-1
- VernacularTitle:ERKs及细胞内游离钙在内皮素-1诱导心肌细胞肥大反应中的作用
- Author:
Wei LU
;
Peiqing LIU
;
Jiang XU
;
Tinghuai WANG
;
Suzhen GONG
;
Jingyun PAN
- Publication Type:Journal Article
- From:
Chinese Journal of Pathophysiology
2001;17(6):496-500
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To study the roles and mechanisms of ERKs and intracellular free calcium in cardiomyocyte hypertrophic response induced by endothelin-1(ET-1). METHODS: (1) Neonatal rat cardiomyocyte hypertrophic response was assayed by measuring cell surface area and protein content; (2) ERKs activity was determined by Whatman Paper Filter method; (3) Intracellular free calcium concentration (［Ca2+］i) was measured using Fura-2/AM as a fluorescent indicator. RESULTS: (1) ET-1 could increase total protein production, surface area, ERKs activity and ［Ca2+］i in cultured cardiomyocyte in dose-dependent manner at concentrations ranging from 10-9 to 10-7 mol/L. And this effect could be abolished by BQ123, an antagonist of ETA receptor, partly inhibited by PTX, but not by BQ788, an antagonist of ETB receptor.（2）The activation of ERKs and the increase of ［Ca2+］i induced by ET-1 were obviously inhibited by PD98059, a selective ERKs kinase inhibitor, and nifedipine, a calcium channel blocker, respectively. Both antagonists partially inhibited ET-1-stimulated cardiomyocyte hypertrophic response. (3) Staurosporine, a selective PKC inhibitor, could inhibit ET-1-stimulated cardiomyocyte hypertrophic response and increase of ［Ca2+］i, but not affect the activation of ERKs. CONCLUSION: Cardiomyocyte hypertrophic response induced by ET-1 is mediated by ETA receptor coupled to PTX-sensitive G-protein, which involves at least two signalling pathways: PKC-mediated increase of ［Ca2+］i , and PKC-independent activation of ERKs.
