Heparin inhibits endothelin-1 and proto-oncogene c-fos gene expression in cultured bovine endothelial cells.
We studied the inhibitory effects of heparin, thrombin inhibitor, and protein kinase C (PKC) inhibitor on basal and thrombin-induced preproendothelin-1 (prepro-ET-1) and proto-oncogene c-fos mRNA expression in cultured bovine endothelial cells (ECs). Northern blot analysis using cDNA for bovine prepro-ET-1 as a probe showed that heparin lowered not only the basal but also the stimulated expression of prepro-ET-1 mRNA by thrombin. A selective thrombin inhibitor (argatroban) and a PKC inhibitor (staurosporine) also inhibited thrombin-induced but not basal prepro-ET-1 mRNA expression. Heparin similarly inhibited thrombin-induced c-fos proto-oncogene mRNA expression in ECs. These data suggest that heparin, in addition to its antithrombin effect, has an inhibitory effect on prepro-ET-1 mRNA expression, possibly via a PKC-dependent pathway.
Imai
T
T
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Hirata
Y
Y
Marumo
F
F
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D015342:DNA Probes; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D006493:Heparin / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D019311:Staurosporine; D013449:Sulfonamides; D013917:Thrombin / Q000494:pharmacology
D000470:Alkaloids; D000991:Antithrombins; D015342:DNA Probes; D019332:Endothelin-1; D016232:Endothelins; D010875:Pipecolic Acids; D011498:Protein Precursors; D012333:RNA, Messenger; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D011493:Protein Kinase C; D013917:Thrombin; D019311:Staurosporine; C031942:argatroban