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 recent ly shown to be expressed in the heart by mechanical stretch and ischem ic injury, we examined the modulation of c-fos mRNA expression and ami no acid uptake by TGF-beta(1) in rat myocardial cells. Pretreatment wi th TGF-beta(1) potentiated norepinephrine (NE)-induced and stretch-ind uced (+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 expre ssion 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 prazos in. The protein kinase C activators (12-O-tetradecanoylphorbol 13-acet ate [TPA], phorbol 12,13-dibutyrate, and 1-oleyl-2-acetyl-rac-glycerol ) induced c-fos mRNA expression, which was also potentiated by TGF-bet a 1. Cycloheximide (protein synthesis inhibitor) could not suppress th e TGF-beta(1) actions. In nonmuscle cells, TGF-beta(1) modified neithe r adrenergic nor TPA-induced c-fos mRNA expression. These data suggest ed that TGF-beta(1) potentiated the c-fos mRNA expression and amino ac id incorporation by modification of the alpha(1)-adrenergic and stretc h-activated protein kinase C pathway. This mechanism did not require p rotein synthesis.