TRANSFORMING GROWTH FACTOR-BETA(1) POTENTIATED ALPHA(1)-ADRENERGIC AND STRETCH-INDUCED C-FOS MESSENGER-RNA EXPRESSION IN RAT MYOCARDIAL-CELLS

Since transforming growth factor-beta(1) (TGF-beta(1)) has been recently shown to be expressed in the heart by mechanical stretch and ischemic injury, we examined the modulation of c-fos mRNA expression and amino acid uptake by TGF-beta(1) in rat myocardial cells. Pretreatment with TGF-beta(1) potentiated norepinephrine (NE)-induced and stretch-induced (+10% and +20% elongation, for 30 minutes) c-fos mRNA expression by 2.2-fold, whereas TGF-beta(1) alone did not induce c-fos mRNA expression in Northern blot analysis. NE-induced [C-14]phenylalanine uptake was also potentiated with TGF-beta(1) pretreatment. The effect of TGF-beta(1) on the NE action was not blocked by propranolol but by prazosin. The protein kinase C activators (12-O-tetradecanoylphorbol 13-acetate [TPA], phorbol 12,13-dibutyrate, and 1-oleyl-2-acetyl-rac-glycerol) induced c-fos mRNA expression, which was also potentiated by TGF-beta 1. Cycloheximide (protein synthesis inhibitor) could not suppress the TGF-beta(1) actions. In nonmuscle cells, TGF-beta(1) modified neither adrenergic nor TPA-induced c-fos mRNA expression. These data suggested that TGF-beta(1) potentiated the c-fos mRNA expression and amino acid incorporation by modification of the alpha(1)-adrenergic and stretch-activated protein kinase C pathway. This mechanism did not require protein synthesis.