© 2005 European Society of Cardiology
p38 MAP-kinase in cultured adult rat ventricular cardiomyocytes: expression and involvement in hypertrophic signalling
Physiologisches Institut, Justus-Liebig-Universität Aulweg 129, D-35392 Giessen, Germany
* Corresponding author. Tel.: +49 641 99 47 255; Fax: +49 641 99 47 219. E-mail address: Sibylle.Wenzel{at}physiologie.med.uni-giessen.de
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Abstract |
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Both 
-adrenoceptor- and β-adrenoceptor-stimulation lead to hypertrophic growth of the myocardium. But only β-adrenoceptor-stimulation requires the pre-cultivation of cells with active TGF-. In order to define signalling molecules that are specifically involved in -adrenoceptor-dependent hypertrophy, changes in expression and hypertrophic responsiveness during pre-cultivation with TGF- were investigated. Isolated adult ventricular cardiomyocytes from rats were either cultured in 20% (v/v) foetal calf serum (FCS) to activate autocrine released TGF-β or used without pre-treatment. Protein synthesis was analysed by 14C-phenylalanine incorporation. Expression of signalling molecules was determined by immunoblotting. During cultivation of cardiomyocytes with active TGF-β only the expression of p38 MAP-kinase increased. Subsequent stimulation of β-adrenoceptors induced protein synthesis in a p38 MAP-kinase-dependent way. However, stimulation of β-adrenoceptors activated p38 MAP-kinase irrespective of pre-treatment with TGF-β. In the absence of this cytokine, hyperosmolarity or reconstitution of mechanical activity increased protein synthesis via p38 MAP-kinase activation in freshly isolated cells. In conclusion, activation of p38 MAP-kinase is a newly identified necessary signalling step required for β-adrenoceptor induced hypertrophic growth. Like activation of adenyl cyclase, activation of p38 MAP-kinase is up-stream of the TGF-β-induced coupling to the regulation of protein synthesis. Reconstitution of mechanical activity mimics the co-activation required and induced by TGF-β.
Key Words: Hyperosmolarity • Mechanical forces • Cardiomyocytes • Hypertrophy
Received April 1, 2004; Revised May 7, 2004; Accepted July 5, 2004