Activation of p70(S6) kinase by beta-adrenoceptor agonists on adult cardiomyocytes.
Cardiac cellular hypertrophy plays an important role in cardiovascular diseases. Up until now, little has been known about the regulation of cellular growth on the level of intracellular signalling. Here, the implication of the p70(S6)-kinase (p70(S6K)) in the hypertrophic response after beta-adrenergic stimulation of cardiac myocytes from adult rats was investigated. Isoproterenol stimulation can activate p70(S6K) in adult cardiomyocytes analysed by direct kinase assays and retarded gel mobility. This signalling of beta-adrenoceptor stimulation is found only under conditions where the cardiomyocytes exhibit also a hypertrophic response to beta-adrenoceptor stimulation as measured by increase in protein content, RNA content and incorporation of radiolabelled amino acids. Rapamycin, a specific inhibitor of this kinase, reduces the trophic responses to control levels, suggesting an involvement of the p70(S6)-kinase in the development of cellular hypertrophy. An engagement of the MAP-kinase (ERK-1/2) pathway in the beta-adrenergic induced growth of cardiac myocytes from adult rats was excluded.
Simm
A
A
Theodor-Boveri-Institut für Biowissenschaften (Biozentrum) der Universität, Physiologische Chemie II, Am Hubland, D-97074 Würzburg, Germany.
Schlüter
K
K
Diez
C
C
Piper
H M
HM
Hoppe
J
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics* / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D010649:Phenylalanine; D019893:Ribosomal Protein S6 Kinases; D007545:Isoproterenol; D020123:Sirolimus