Increased basal contractility of cardiomyocytes overexpressing protein kinase Cε and blunted positive inotropic response to endothelin-1

被引:19
作者
Baudet, S
Weisser, J
Janssen, AP
Beulich, K
Bieligk, U
Pieske, B
Noireaud, J
Janssen, PML
Hasenfuss, G
Prestle, J
机构
[1] Univ Gottingen, Zentrum Innere Med, Dept Cardiol & Pneumol, D-37075 Gottingen, Germany
[2] Univ Freiburg, Dept Cardiol & Angiol, D-79106 Freiburg, Germany
[3] INSERM, U533, F-44035 Nantes 01, France
关键词
contractile function; e-c coupling; endothelins; gene therapy; myocytes; protein kinases; signal transduction;
D O I
10.1016/S0008-6363(01)00225-5
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Protein kinase C (PKC) is thought to be involved in the regulation of the mammalian cardiac excitation-contraction coupling process by vasoactive peptides Like endothelin-1 (ET-1). However, the demonstration of a causal link between activation of specific PKC isoforms and the increase in contractility mediated by ET-1 is still inferential. Methods: By means of adenovirus-mediated gene transfer, we specifically overexpressed PKC epsilon in cultured adult rabbit Ventricular myocytes (Ad-PKC epsilon). Myocyte shortening and [Ca2+](i) transients under basal and ET-1-stimulated conditions were measured in Ad-PKC epsilon and Ad-LacZ control transfected cells. Results: Infection with Ad-PKC epsilon resulted in a strong, virus dose-dependent increase in PKC epsilon protein Levels, whereas protein expression of other PKC isoforms remained unchanged. Using a multiplicity of infection of 100 plaque-forming units/myocyte, basal and cofactor-dependent PKC epsilon kinase activity was increased 28- and 90-fold, respectively, when compared to control. Myocyte basal fractional shortening and [Ca2+](i), transient amplitude were both increased by 21% (P<0.05 each) in Ad-PKC<epsilon> transfected myocytes when compared to Ad-LacZ transfected control myocytes. The positive Inotropic effect of ET-1 in control myocytes was markedly blunted in PKC epsilon -overexpressing myocytes. Conclusion: Specific overexpression of PKC epsilon in rabbit ventricular myocytes increases basal myocyte contractility and [Ca2+](i) transients, and modifies their responsiveness to ET-1. (C) 2001 Elsevier Science B.V. AII rights reserved.
引用
收藏
页码:486 / 494
页数:9
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