Regulation of c-Fos and c-Jun gene expression by phospholipase C activity in adult cardiomyocytes

Abstract

This study was undertaken to determine whether gene expression for transcriptional factors such as c-Fos and c-Jun is regulated by phospholipase C (PLC) activity. Norepinephrine (NE) increased PLC beta(1), beta(3), gamma(1), and delta(1) isozyme gene expression, protein contents and their activities in adult rat cardiomyocytes. Increases in PLC beta(1), beta(3), gamma(1), and delta(1) activities and gene expression in response to NE were prevented by prazosin, an alpha(1)-adrenoceptor (AR) antagonist. Furthermore, mRNA levels for c-Fos and c-Jun, unlike other transcriptional factors, were increased by both NE and phenylephrine, a specific alpha(1)-AR agonist. Increases in c-Fos and c-Jun gene expression due to NE were attenuated by both prazosin and a PLC inhibitor, U73122. Activation of protein kinase C (PKC) with phorbol myristate acetate increased c-Fos and c-Jun mRNA, whereas inhibition of PKC with bisindolylmaleimide as well as inhibition of extracellular signal-regulated kinases (ERK) 1/2 with PD98059 abolished the NE-induced increase in c-Fos and c-Jun gene expression. Reduction of c-Jun phosphorylation by SP600125, an inhibitor of JNK activity, was associated with an attenuation of the NE-induced increases in PLC gene expression. It is suggested that c-Fos and c-Jun gene expression is regulated by PLC in adult cardiomyocytes through a PKC- and ERK1/2-dependent pathway.