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Cardiovascular Research 1998 40(1):174-181; doi:10.1016/S0008-6363(98)00171-0
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Role of phosphatidylinositol 3-kinase activation in the hypertrophic growth of adult ventricular cardiomyocytes

Klaus-Dieter Schlüter*, Yaron Goldberg, Gerhild Taimor, Matthias Schäfer and Hans Michael Piper

Physiologisches Institut, Universität Giessen, Aulweg 129, D-35392 Giessen, Germany

* Corresponding author. Tel.: +49-641-994-7243; Fax: +49-641-994-7239; E-mail: klaus-dieter.schlueter@physiologie.med.uni-giessen.de

Objective: The present study investigated whether activation of phosphatidylinositol 3-kinase (PI3-kinase) is involved in the stimulation of hypertrophic growth of adult ventricular cardiomyocytes under {alpha}- or β-adrenoceptor stimulation. Methods: Adult ventricular rat cardiomyocytes were used either directly after isolation (day 1 culture) or after cultivation for 6 days in presence of 20% fetal calf serum (day 7 culture). PI3-kinase activity was determined in extracts of cardiomyocytes after immunoprecipitation with an antibody against the p85 subunit of PI3-kinase. The influence of PI3-kinase inhibition on myocardial growth was determined using the specific PI3-kinase inhibitors wortmannin and LY294002. Results: In day 1 cultures {alpha}-adrenoceptor stimulation, but not β-adrenoceptor stimulation caused activation of PI3-kinase. In response to {alpha}-adrenoceptor stimulation but not β-adrenoceptor stimulation an acceleration of protein synthesis (incorporation of 14C-phenylalanine) and an increase in the total masses of cellular protein and RNA was observed. In these cultures inhibition of PI3-kinase attenuated the acceleration of protein synthesis and the increase in cellular masses of protein or RNA in response to {alpha}-adrenoceptor stimulation. In day 7 cultures {alpha}- and β-adrenoceptor stimulation caused activation of PI3-kinase and increased protein synthesis. In these cultures inhibition of PI3-kinase attenuated the growth response to {alpha}- and β-adrenoceptor stimulation. Conclusions: PI3-kinase activation via protein kinase C-dependent or cAMP-dependent pathways is required for hypertrophic growth of adult cardiomyocytes.

KEYWORDS Hypertrophy; Myocytes; Protein kinases; Second messengers; Signal transduction


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