RAC1
活性氧
下调和上调
激活剂(遗传学)
细胞生物学
转录因子
纤溶
纤溶酶原激活物抑制剂-1
纤溶酶原激活剂
缺氧(环境)
生物
信号转导
小型GTPase
分子生物学
缺氧诱导因子
化学
生物化学
基因
内分泌学
氧气
内科学
医学
有机化学
作者
Agnes Görlach,Utta Berchner‐Pfannschmidt,Christoph Wotzlaw,Robbert H. Cool,Joachim Fandrey,H. Acker,Kurt Jungermann,Thomas Kietzmann
出处
期刊:Thrombosis and Haemostasis
[Georg Thieme Verlag KG]
日期:2003-01-01
卷期号:89 (05): 926-935
被引量:61
标识
DOI:10.1055/s-0037-1613480
摘要
Summary The hypoxia-inducible transcription factor HIF-1 mediates upregulation of plasminogen activator inhibitor-1 (PAI-1) expression under hypoxia. Reactive oxygen species (ROS) have also been implicated in PAI-1 gene expression. However, the role of ROS in HIF-1-mediated regulation of PAI-1 is not clear. We therefore investigated the role of the GTPase Rac1 which modulates ROS production in the pathway leading to HIF-1 and PAI-1 induction. Overexpression of constitutively activated (RacG12V) or dominant-negative (RacT17N) Rac1 increased or decreased, respectively, ROS production. In RacG12V-expressing cells, PAI-1 mRNA levels as well as HIF-1α nuclear presence were reduced under normoxia and hypoxia whereas expression of RacT17N resulted in opposite effects. Treatment with the antioxidant pyrrolidinedithiocarbamate or coexpression of the redox factor-1 restored HIF-1 and PAI-1 promoter activity in RacG12V-cells. In contrast, NFκB activation was enhanced in RacG12V-cells, but abolished by RacT17N. Thus, these findings suggest a mechanism explaining modified fibrinolysis and tissue remodeling in an oxidized environment.
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