Increased basal contractility of cardiomyocytes overexpressing protein kinase C epsilon and blunted positive inotropic response to endothelin-1
2001 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Increased basal contractility of cardiomyocytes overexpressing protein kinase C epsilon and blunted positive inotropic response to endothelin-1
Baudet, S.; Weisser, J.; Janssen, A. P.; Beulich, K .; Bieligk, U.; Pieske, B. & Noireaud, J. et al. (2001)
Cardiovascular Research, 50(3) pp. 486-494. DOI: https://doi.org/10.1016/S0008-6363(01)00225-5
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- Authors
- Baudet, S.; Weisser, J; Janssen, A. P.; Beulich, K .; Bieligk, U.; Pieske, Burkert ; Noireaud, J; Janssen, P. M. L.; Hasenfuß, Gerd ; Prestle, J.
- Abstract
- 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.
- Issue Date
- 2001
- Publisher
- Elsevier Science Bv
- Journal
- Cardiovascular Research
- ISSN
- 0008-6363