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
;
Jingyu PAN
- Publication Type:Journal Article
- Keywords:
Endothelium;
Calcium;
Cardiomyopathy, hypertrophic;
G-proteins;
Protein kinase C
- From:
Chinese Journal of Pathophysiology
1989;0(06):-
- 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 ([Ca 2+ ]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 [Ca 2+ ]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 ET A receptor, partly inhibited by PTX, but not by BQ788, an antagonist of ET B receptor.(2)The activation of ERKs and the increase of [Ca 2+ ]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 [Ca 2+ ]i, but not affect the activation of ERKs. CONCLUSION: Cardiomyocyte hypertrophic response induced by ET-1 is mediated by ET A receptor coupled to PTX-sensitive G-protein, which involves at least two signalling pathways: PKC-mediated increase of [Ca 2+ ]i , and PKC-independent activation of ERKs. [
