Angiotensin II-induced protein phosphorylation in the hypertrophic heart of the Dahl rat.
Angiotensin II-induced phosphorylation of proteins was examined in isolated myocytes from hearts of Dahl rats. A high salt diet induced cardiac hypertrophy in Dahl salt-sensitive rats. Angiotensin II-induced phosphorylation of a 42-kd protein (pp42) was detected by two-dimensional electrophoresis in hypertrophic but not normal ventricular myocytes. Angiotensin II stimulation was time-dependent, with a peak effect at 30 minutes. The half-maximal and maximal concentrations of angiotensin II that stimulated pp42 phosphorylation were 1 and 10 nM, respectively. Phosphorylation of pp42 was a function of cardiac hypertrophy. Phorbol 12-myristate 13-acetate-induced phosphorylation of pp42 indicates the possibility of an association between protein kinase C and the signal transduction pathway of angiotensin II-induced pp42 phosphorylation. Ionomycin and A23187 (both at 1 microM) did not stimulate phosphorylation of pp42. Angiotensin II produced a small increase in the synthesis of myocyte proteins in both normal and hypertrophic cells as shown by [35S]methionine incorporation. However, this increase could not account for the increase in the phosphate content of pp42. This protein was not an isoform of actin nor was it of platelet origin. These results raise the possibility that angiotensin II may play a role in the activation of factors in hypertrophic myocytes; however, further study is required to define a link between phosphorylation of pp42 and the hypertrophic process.
Sunga
P S
PS
University Hospital Research Centre (Shaughnessy Site), University of British Columbia, Vancouver, Canada.
Rabkin
S W
SW
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D006332:Cardiomegaly / Q000378:metabolism*; D002469:Cell Separation; D004351:Drug Resistance / Q000235:genetics; D004586:Electrophoresis; D015759:Ionomycin / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000737:chemistry; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009124:Muscle Proteins; D010750:Phosphoproteins; D000804:Angiotensin II; D000001:Calcimycin; D012965:Sodium Chloride; D015759:Ionomycin; D008715:Methionine; D013755:Tetradecanoylphorbol Acetate