肝素可抑制培养的牛内皮细胞中内皮素 -1 和原癌基因 c-fos 的基因表达。

Heparin inhibits endothelin-1 and proto-oncogene c-fos gene expression in cultured bovine endothelial cells.

作者信息

Imai T, Hirata Y, Marumo F

机构信息

Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.

出版信息

J Cardiovasc Pharmacol. 1993;22 Suppl 8:S49-52. doi: 10.1097/00005344-199322008-00015.

DOI:10.1097/00005344-199322008-00015

PMID:7509997

Abstract

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.

摘要

我们研究了肝素、凝血酶抑制剂和蛋白激酶C（PKC）抑制剂对培养的牛内皮细胞（ECs）中基础状态以及凝血酶诱导的前内皮素原-1（prepro-ET-1）和原癌基因c-fos mRNA表达的抑制作用。使用牛prepro-ET-1 cDNA作为探针的Northern印迹分析表明，肝素不仅降低了基础状态下的prepro-ET-1 mRNA表达，还降低了凝血酶刺激后的表达。一种选择性凝血酶抑制剂（阿加曲班）和一种PKC抑制剂（星形孢菌素）也抑制了凝血酶诱导的而非基础状态下的prepro-ET-1 mRNA表达。肝素同样抑制了ECs中凝血酶诱导的c-fos原癌基因mRNA表达。这些数据表明，肝素除了具有抗凝血酶作用外，还可能通过PKC依赖途径对prepro-ET-1 mRNA表达具有抑制作用。