The AP-1 site is essential for the promoter activity of NOX1/NADPH oxidase, a vascular superoxide-producing enzyme: Possible involvement of the ERK1/2-JunB pathway
The AP-1 site is essential for the promoter activity of NOX1/NADPH oxidase, a vascular superoxide-producing enzyme: Possible involvement of the ERK1/2-JunB pathway
复制标题
DOI：
10.1016/j.bbrc.2008.07.027
复制
发表时间：
2008-09-19
影响因子：
3.1
通讯作者：
Yabe-Nishimura, Chihiro
中科院分区：
文献类型：
--
作者：
Cevik, Muhammer Ozgur;Katsuyama, Masato;Yabe-Nishimura, Chihiro
NADPH氧化酶是心血管组织中产生超氧化物的主要来源。NOX1是NADPH氧化酶的催化亚基，其表达可由多种血管活性因子诱导，包括血管紧张素11、前列腺素（PG） F-2 α和血小板衍生生长因子（PDGF）。先前有报道称，NOX1的诱导表达受磷酸化肌苷3（1113）激酶下游级联的活化转录因子-1 (ATF-1)-肌细胞增强因子213 （MEF2B）的调控。也有报道称细胞外信号调节激酶（ERK） 1/2参与了NOX1的表达。为了进一步明确ERK1/2下游NOX1诱导的相关因素，我们分析了NOX1基因的启动子区域。在大鼠NOX1基因5'侧区-98/-92处发现了一个一致的激活蛋白-1 （AP-1）位点。在荧光素酶试验中，在该位点引入突变可消除PGF（2 α）诱导的转录激活。电泳迁移率转移实验表明，PGF（2 α）和PDGF增强了JunB与该序列的结合。MAPK/ERK激酶抑制剂PD98059抑制PGF（2 α）或PDGF诱导的JunB的表达。这些结果表明，ERK1/2-JunB通路是血管平滑肌细胞诱导表达NOX1基因的关键调控因子。(C) 2008爱思唯尔公司版权所有。
NADPH oxidase is a major source of the superoxide produced in cardiovascular tissues. The expression of NOX1, a Catalytic Subunit of NADPH oxidase, is induced by various vasoactive factors, including angiotensin 11, prostaglandin (PG) F-2 alpha, and platelet-derived growth factor (PDGF). It was reported previously that the inducible expression of NOX1 is governed by the activating transcription factor-1 (ATF-1)-myocyte enhancer factor 213 (MEF2B) cascade downstream of phosphoinositide 3 (1113) kinase. It was also reported that extracellular signal-regulated kinase (ERK) 1/2 is involved in the expression of NOX1. To further clarify the factors involved in NOX1 induction downstream of ERK1/2, the promoter region of the NOX1 gene was analyzed. A consensus activator protein-1 (AP-1) site was found at -98/-92 in the 5'-flanking region of the rat NOX1 gene. The introduction Of Mutations at this site abolished PGF(2 alpha)-induced transcriptional activation in a luciferase assay. Electrophoresis mobility shift assays demonstrated that PGF(2 alpha) and PDGF augmented the binding of JunB to this sequence. PD98059, an inhibitor of MAPK/ERK kinase, suppressed the expression of JunB induced by PGF(2 alpha) or PDGF. These results suggest that the ERK1/2-JunB pathway is a key regulator of the inducible expression of the NOX1 gene in vascular smooth muscle cells. (C) 2008 Elsevier Inc. All rights reserved.