Transforming growth factor-beta 1 potentiated alpha 1-adrenergic and stretch-induced c-fos mRNA 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 [14C]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.
First Department of Internal Medicine, Kobe University School of Medicine, Japan.
N
N
Miki
Y
Y
Hamamori
K
K
Hirata
M
M
Suematsu
S
S
Kawashima
H
H
Akita
M
M
Yokoyama
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D016762:Genes, fos; D016259:Genes, myc; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000596:Amino Acids; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D016212:Transforming Growth Factor beta; D003513:Cycloheximide; D011493:Protein Kinase C; D009638:Norepinephrine