Induction of the c-jun proto-oncogene by a protein kinase c-dependent mechanism during exposure of human epidermal keratinocytes to ethanol

Abstract

The present work demonstrates that ethanol induces expression of the c- jun proto-oncogene in human keratinocytes. Increased c- jun mRNA levels were detectable at 1 hr of exposure to 1 % ethanol and at 24 hr remained above that in control keratinocytes. An increase in c- jun expression was also detectable at ethanol concentrations of 0.1 and 0.5%. Similar findings were obtained for the related jun- B and c- fos early response genes. The results also demonstrate that ethanol exposure is associated with increases in protein kinase C activity in both the cytosol and membrane fractions. This increase was detectable at 5 min and maximal at 30–60 min. The finding that induction of c- jun expression by ethanol was inhibited by the isoquinolinesulfonamide derivative H7, but not by HA1004, suggested that this effect is mediated by protein kinase C. Furthermore, down-regulation of protein kinase C by prolonged exposure to 12- O-tetradecanoylphorbol-13-acetate was associated with a block in ethanol-induced c- jun expression. We also demonstrated that ethanol exposure is associated with rapid (5–30 min) increases in intracellular levels of diradylglycerol. Taken together, these findings demonstrate that the exposure of keratinocytes to ethanol results in the activation of protein kinase C and c- jun expression.