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

• Published in: Cardiovascular research Vol. 40; no. 1; pp. 174 - 181
• Main Authors: SCHLÜTER, K.-D, GOLDBERG, Y, TAIMOR, G, SCHÄFER, M, PIPER, H. M
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.1998
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic beta-Agonists - pharmacology; Androstadienes - pharmacology; Animals; Biological and medical sciences; Cardiology. Vascular system; Cardiomegaly - enzymology; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cells, Cultured; Chromatography, Thin Layer; Chromones - pharmacology; DNA - analysis; Enzyme Activation; Enzyme Inhibitors - pharmacology; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Isoproterenol - pharmacology; Male; Medical sciences; Morpholines - pharmacology; Myocardium - enzymology; Myocardium - metabolism; Myocardium - pathology; Phenylalanine - metabolism; Phenylephrine - pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - physiology; Protein Biosynthesis; Rats; Rats, Wistar; RNA - analysis; Signal Transduction; Stimulation, Chemical; Time Factors; Uridine - metabolism; Wortmannin; Human; Heart; Cell proliferation; Cell culture; Rat; Enzyme; Pathogenesis; Transferases; Rodentia; Cardiovascular disease; Activation; Myocyte; Phosphatidylinositol; Signal transduction; Vertebrata; Mammalia; Kinase; Heart disease; Animal; Adult; Hypertrophy
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/s0008-6363(98)00171-0

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 beta-adrenoceptor stimulation. 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. In day 1 cultures alpha-adrenoceptor stimulation, but not beta-adrenoceptor stimulation caused activation of PI3-kinase. In response to alpha-adrenoceptor stimulation but not beta-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 beta-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 beta-adrenoceptor stimulation. PI3-kinase activation via protein kinase C-dependent or cAMP-dependent pathways is required for hypertrophic growth of adult cardiomyocytes.