Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Baudet, S; Weisser, J; Janssen, AP; Beulich, K; Bieligk, U; Pieske, B; Noireaud, J; Janssen, PM; Hasenfuss, G; Prestle, J.
Increased basal contractility of cardiomyocytes overexpressing protein kinase C epsilon and blunted positive inotropic response to endothelin-1.
Cardiovasc Res. 2001; 50(3):486-494
Doi: 10.1016/S0008-6363(01)00225-5
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- Co-Autor*innen der Med Uni Graz
- Pieske Burkert Mathias
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenoviridae - genetics
- Animals - genetics
- Calcium - metabolism
- Cardiotonic Agents - pharmacology
- Cell Culture Techniques - pharmacology
- Dose-Response Relationship, Drug - pharmacology
- Endothelin-1 - pharmacology
- Gene Transfer Techniques - pharmacology
- Genetic Vectors - pharmacology
- Heart Ventricles - cytology
- Myocardial Contraction - drug effects
- Myocardium - enzymology
- Protein Kinase C - metabolism
- Rabbits - metabolism
- Find related publications in this database (Keywords)
- contractile function
- e-c coupling
- endothelins
- gene therapy
- myocytes
- protein kinases
- signal transduction