The role of c-Jun protein in thrombin-stimulated expression of preproendothelin-1 mRNA in porcine aortic endothelial cells.
Treatment of porcine aortic endothelial cells with thrombin induced a time- and dose-dependent expression of preproendothelin-1 (PPET-1) mRNA. The thrombin-induced expression of PPET-1 mRNA was markedly inhibited by calphostin C, a specific inhibitor of protein kinase C, and phorbol 12-myristate 13-acetate (TPA) induced the expression of PPET-1 mRNA dose-dependently, but 4 alpha-phorbol 12, 13-didecanoate, an inactive enantiomer of phorbol ester, had no effect on the expression of PPET-1 mRNA. On the other hand, challenge of the endothelial cells with thrombin induced a marked and time-dependent increase in the binding activity of nuclear extract to the TPA-responsive element. Furthermore, thrombin elicits synthesis of c-Jun protein as well as triggering its dephosphorylation. From these results, it is concluded that thrombin-stimulated expression of PPET-1 mRNA in porcine aortic endothelial cells can be induced not only by c-Jun protein synthesis but also by initial dephosphorylation in response to activation of protein kinase C.
Kitazumi
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Tasaka
K
K
D000818:Animals; D001011:Aorta; D001483:Base Sequence; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D019332:Endothelin-1; D016232:Endothelins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis*; D013552:Swine; D013917:Thrombin / Q000494:pharmacology
D003470:Culture Media; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D013917:Thrombin