...
首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >Posttranscriptional regulation of expression of plasminogen activator inhibitor type-1 by sphingosine 1-phosphate in HepG2 liver cells
【24h】

Posttranscriptional regulation of expression of plasminogen activator inhibitor type-1 by sphingosine 1-phosphate in HepG2 liver cells

机译:鞘氨醇1-磷酸在HepG2肝细胞中对纤溶酶原激活物抑制剂1型表达的转录后调控

获取原文
获取原文并翻译 | 示例
           

摘要

Altered expression of plasminogen activator inhibitor type-1 (PAI-1), a major physiologic inhibitor of fibrinolysis, is implicated in the progression of atherosclerosis. Sphingosine 1-phosphate (S1P) regulates expression of diverse genes and alters expression of PAI-1 in several types of cells. However, the nature of posttranscriptional regulation of expression of PAI-1 by S1P has not yet been thoroughly elucidated. The present study was undertaken to determine whether S1P has important effects on the posttranscriptional regulation of PAI-1 expression. To evaluate this possibility, we determined promoter activity, mRNA levels, 3'-untranslated region (UTR) activity, and protein levels of PAI-1 in HepG2 cells. S1P increased PAI-1 promoter activity and the expression of PAI-1 mRNA within 4. h of exposure. It decreased the expression of PAI-1 mRNA and the accumulation of PAI-1 protein into the media in 24. h. Human PAI-1 mRNA exists in two subspecies (3.2 and 2.2. kb). S1P decreased the baseline luciferase activity of the 1. kb fragment of the 3' terminus (+. 2177 to 3176. nt) of the 3'-UTR of the 3.2. kb PAI-1 mRNA [3'-UTR (+. 2177-3176)]. S1P decreased expression of PAI-1 protein, presumably by regulating PAI-1 expression at the posttranscriptional level thereby affecting mRNA stability. SERPINE1 mRNA binding protein (SERBP1) and ARE3 in the 3'-UTR were involved in the posttranscriptional regulation by S1P. Our data suggest that S1P can destabilize 3.2. kb PAI-1 mRNA through specific effects on the 3'-UTR. These effects appear to involve SERBP1 leading to decreased expression of PAI-1 protein.
机译:纤溶酶的主要生理抑制剂纤溶酶原激活物抑制剂1型(PAI-1)的表达改变与动脉粥样硬化的发展有关。 1-磷酸鞘氨醇(S1P)调节多种基因的表达并改变PAI-1在几种类型细胞中的表达。然而,尚未完全阐明S1P对PAI-1表达的转录后调控的性质。进行本研究以确定S1P是否对PAI-1表达的转录后调控有重要影响。为了评估这种可能性,我们确定了HepG2细胞中启动子活性,mRNA水平,3'-非翻译区(UTR)活性和PAI-1的蛋白水平。 S1P在暴露后4小时内增加了PAI-1启动子活性和PAI-1 mRNA的表达。在24小时内,它降低了PAI-1 mRNA的表达和PAI-1蛋白向培养基中的积累。人PAI-1 mRNA存在于两个亚种(3.2和2.2。kb)中。 S1P降低了3.2的3'-UTR的3'末端的1. kb片段(+。2177至3176. nt)的基线荧光素酶活性。 kb PAI-1 mRNA [3'-UTR(+。2177-3176)]。 S1P可能通过在转录后水平上调节PAI-1表达从而降低了mRNA的稳定性而降低了PAI-1蛋白的表达。 3'-UTR中的SERPINE1 mRNA结合蛋白(SERBP1)和ARE3参与S1P的转录后调控。我们的数据表明,S1P可能会破坏3.2。 kb PAI-1 mRNA通过对3'-UTR的特异性作用。这些作用似乎涉及SERBP1,导致PAI-1蛋白表达降低。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号