STIMULATION OF PROTEIN-SYNTHESIS BY PHOSPHATIDIC-ACID IN RAT CARDIOMYOCYTES

Phosphatidic acid (PA) was observed to stimulate protein synthesis in adult cardiomyocytes in a time- and concentration-dependent manner. Th e maximal stimulation in protein synthesis (142 +/- 12% vs 100% as the control) was achieved at 10 mu M PA within 60 min and was inhibited b y actinomycin D (107 +/- 4% of the control) or cycloheximide (105 +/- 6% of the control). The increase in protein synthesis due to PA was at tenuated or abolished by preincubation of cardiomyocytes with a tyrosi ne kinase inhibitor, genistein (94 +/- 9% of the control), phospholipa se C inhibitors 2-nitro-4-carboxyphenyl N,N-diphenyl carbamate or carb onodithioic acid O-(octahydro-4,7-methanol-1H-inden-5-yl (101 +/- 6 an d 95 +/- 5% of the control, respectively), protein kinase C inhibitors staurosporine or polymyxin B (109 +/- 3 and 93 +/- 3% of the control) , and chelators of extracellular and intracellular free Ca2+ EGTA or B APTA/AM (103 +/- 6 and 95 +/- 6% of the control, respectively). PA at different concentrations (0.1 to 100 mu M) also caused phosphorylation of a cell surface protein of approximately 24 kDa. In addition, mitog en-activated protein kinase was stimulated by PA in a concentration-de pendent manner; maximal stimulation (217 +/- 6% of the control) was se en at 10 mu M PA. These data suggest that PA increases protein synthes is in adult rat cardiomyocytes and thus may play an important role in the development of cardiac hypertrophy. Copyright (C) 1996 Elsevier Sc ience Inc.