Transforming growth factor-β1 potentiated α1-adrenergic and stretch-induced c-fos mRNA expression in rat myocardial cells

Abstract

Since transforming growth factor-β1 (TGF-β1) 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-(β1 in rat myocardial cells. Pretreatment with TGF-β1 potentiated norepinephrine (NE)-induced and stretch-induced (+10% and +20% elongation, for 30 minutes) c-fos mRNA expression by 2.2-fold, whereas TGF-β1 alone did not induce c-fos mRNA expression in Northern blot analysis. NE-induced [14C]phenylalanine uptake was also potentiated with TGF-β1 pretreatment. The effect of TGF-β1 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-β1. Cycloheximide (protein synthesis inhibitor) could not suppress the TGF-β1 actions. In nonmuscle cells, TGF-β1 modified neither adrenergic nor TPA-induced c-fos mRNA expression. These data suggested that TGF-β1 potentiated the c-fos mRNA expression and amino acid incorporation by modification of the α1-adrenergic and stretch-activated protein kinase C pathway. This mechanism did not require protein synthesis.