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


CONCLUSIONS
PI3-kinase activation via protein kinase C-dependent or cAMP-dependent pathways is required for hypertrophic growth of adult cardiomyocytes.
Schlüter
K D
KD
Physiologisches Institut, Universität Giessen, Giessen, Germany. klaus-dieter.schlucter@physiologic.med.uni-giessen.de
Goldberg
Y
Y
Taimor
G
G
Schäfer
M
M
Piper
H M
HM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D002867:Chromones / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010649:Phenylalanine / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014176:Protein Biosynthesis; D012313:RNA / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013268:Stimulation, Chemical; D013997:Time Factors; D014529:Uridine / Q000378:metabolism; D000077191:Wortmannin
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D002867:Chromones; D004247:DNA; D004791:Enzyme Inhibitors; D007545:Isoproterenol; D009025:Morpholines; D010649:Phenylalanine; D010656:Phenylephrine; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012313:RNA; D014529:Uridine; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one