Regulation of the hypoxia-dependent plasminogen activator inhibitor 1 expression by MAP kinases
Regulation of the hypoxia-dependent plasminogen activator inhibitor 1 expression by MAP kinases
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MAP 激酶对缺氧依赖性纤溶酶原激活剂抑制剂 1 表达的调节
DOI：
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发表时间：
2003
影响因子：
6.7
通讯作者：
A. Görlach
中科院分区：
文献类型：
--
作者：
T. Kietzmann;K. Jungermann;A. Görlach
摘要丝裂原活化蛋白激酶(MAPKs)和蛋白激酶B(PKB)介导生长和应激信号，并与低氧反应有关。在低氧条件下，纤溶酶原激活物抑制物-1(PAI-1)的表达主要受缺氧诱导因子HIF-1的调控。然而，MAPKs和PKB在HIF-1介导的PAI-1调控中的作用尚不清楚。用p38抑制剂SB203580和PI3K抑制剂LY294002处理，而不用MEK1抑制剂PD98059处理，可抑制低氧依赖的PAI-1在HepG2细胞中的诱导。持续地，PKB或p38上游的MKK6和MKK3以及JNK的过度表达，而不是ERK的过度表达，促进了PAI-1mRNA的表达。在表达MKK3、MKK6和PKB的细胞中，低氧诱导的PAI1-LUC和依赖于HIF的LUC的荧光素酶(LUC)活性以及相应的HIF-1α蛋白水平均增强。这些发现表明，依赖p38和PKB的信号通路有助于缺氧反应中PAI-1水平的升高。主题论文：本论文的一部分最初是在2002年9月在德国慕尼黑举行的第16届国际纤维蛋白溶解和蛋白分解学会(ISFP)国际大会和第17届国际纤维蛋白原研究会(IFRS)国际纤维蛋白原研讨会上提交的。
Summary Mitogen-activated protein kinases (MAPKs) and protein kinase B (PKB) mediate growth and stress signals and have been implicated in the hypoxic response. Under hypoxic conditions, the expression of plasminogen activator inhibitor-1 (PAI-1) is mainly controlled by the hypoxia-inducible factor HIF-1. However, the role of MAPKs and PKB in HIF-1-mediated PAI-1 regulation is not clear. Treatment with the p38 inhibitor SB203580 and the PI3K inhibitor LY294002, but not with the MEK1 inhibitor PD98059, abrogated hypoxia-dependent PAI-1 induction in HepG2 cells. Consistently, overexpression of PKB or of the p38 upstream kinases MKK6 and MKK3 and of JNK, but not of ERK, enhanced PAI-1 mRNA levels. In MKK3-,MKK6- and PKB-expressing cells luciferase (Luc) activities from a hypoxia-inducible PAI-1-Luc construct or from a HIF-dependent Luc construct and, concomitantly, HIF-1α protein levels were enhanced. These findings indicate that p38- and PKB-dependent signalling pathways contribute to enhanced PAI-1 levels in the hypoxic response. Theme paper: Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.
影响因子：
15.9
作者：
Eitzman, DT;McCoy, RD;Simon, RH
通讯作者：
Simon, RH
DOI：
10.1006/bbrc.2001.5532
发表时间：
2001-09-14
影响因子：
3.1
作者：
Sodhi, A;Montaner, S;Gutkind, JS
通讯作者：
Gutkind, JS
影响因子：
11.2
作者：
D. Feldser;F. Agani;N. Iyer;Brian Pak;Gloria C. Ferreira;G. Semenza
通讯作者：
D. Feldser;F. Agani;N. Iyer;Brian Pak;Gloria C. Ferreira;G. Semenza