THE ROLE OF C-JUN PROTEIN IN THROMBIN-STIMULATED EXPRESSION OF PREPROENDOTHELIN-1 MESSENGER-RNA IN PORCINE AORTIC ENDOTHELIAL-CELLS

Treatment of porcine aortic endothelial cells with thrombin induced a time- and dose-dependent expression of preprendothelin-1 (PPET-1) mRNA . The thrombin-induced expression of PPET-1 mRNA was markedly inhibite d by calphostin C, a specific inhibitor of protein kinase C, and phorb ol 12-myristate 13-acetate (TPA) induced the expression of PPET-1 mRNA dose-dependently, but 4alpha-phorbol 12, 13-didecanoate, an inactive enantiomer of phorbol ester, had no effect on the expression of PPET-1 m RNA. On the other hand, challenge of the endothelial cells with thro mbin induced a marked and time-dependent increase in the binding activ ity of nuclear extract to the TPA-responsive element. Furthermore, thr ombin elicits synthesis of c-Jun protein as well as triggering its dep hosphorylation. From these results, it is concluded that thrombin-stim ulated expression of PPET-1 mRNA in porcine aortic endothelial cells c an be induced not only by c-Jun protein synthesis but also by initial dephosphorylation in response to activation of protein kinase C.