Effect of protein kinase C on cyclic 3',5'-adenosine monophosphate-dependent phosphodiesterase in hypertrophic cardiomyopathic hamster hearts.
"Cross-talk," or interaction between different signal transduction pathways, is known to exist in noncardiac cells, but it has not been demonstrated previously in mammalian hearts. We found that hypertrophic cardiomyopathic Syrian hamster (BIO 14.6, 6 months old) hearts were deficient in cyclic 3',5'-adenosine monophosphate (cAMP) [11.9 +/- 0.4 vs. 15.4 +/- 0.4 pmol/mg protein in age-matched control hamsters (BIO RB), n = 6, P = .0005] but not in cyclic 3',5'-guanosine monophosphate (1.23 +/- 0.10 vs. 1.34 +/- 0.18 pmol/mg protein in BIO RB, n = 6, P = N.S.). The reduction in cAMP was at least partly accounted for by an increase in the cytosolic phosphodiesterase (PDE) activity in BIO 14.6 hearts (1709 +/- 119 vs. 1341 +/- 113 pmol/min/mg protein in age-matched BIO RBs, n = 12, P = .006), suggesting that there is an increase in cAMP turnover in BIO 14.6 hearts. Protein kinase C (PKC) activities were also significantly elevated in BIO 14.6 hearts (77.9 +/- 2.1 vs. 54.6 +/- 3.3 pmol/min/mg protein in BIO RBs, n = 6, P < .001). Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 10 microM) produced significant potentiation in PDE activities in BIO 14.6 but not in BIO RB hearts, and the PMA-induced increase in PDE activity could be blocked by the PKC-specific pseudosubstrate inhibitor peptide PKC(19-31).(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
H C
HC
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Cai
J J
JJ
Yu
H
H
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology*; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D008647:Mesocricetus; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
D000242:Cyclic AMP; D011493:Protein Kinase C; D015105:3',5'-Cyclic-AMP Phosphodiesterases