Nox4过表达激活人内皮细胞中的活性氧和p38丝裂原活化蛋白激酶。
Nox4 overexpression activates reactive oxygen species and p38 MAPK in human endothelial cells.
作者信息
Goettsch Claudia, Goettsch Winfried, Muller Gregor, Seebach Jochen, Schnittler Hans-Joachim, Morawietz Henning
机构信息
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University of Technology Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.
出版信息
Biochem Biophys Res Commun. 2009 Mar 6;380(2):355-60. doi: 10.1016/j.bbrc.2009.01.107.
Nicotine adenine dinucleotide phosphate (NADPH) oxidase (Nox) complexes are the main sources of reactive oxygen species (ROS) formation in the vessel wall. We have used DNA microarray, real-time PCR and Western blot to demonstrate that the subunit Nox4 is the major Nox isoform in primary human endothelial cells; we also found high levels of NADPH oxidase subunit p22(phox) expression. Nox4 was localized by laser scanning confocal microscopy within the cytoplasm of endothelial cells. Endothelial Nox4 overexpression enhanced superoxide anion formation and phosphorylation of p38 MAPK. Nox4 down-regulation by shRNA has in contrast to TGF-beta no effect on p38 MAPK phosphorylation. We conclude that Nox4 is the major Nox isoform in human endothelial cells, and forms an active complex with p22(phox). The Nox4-containing complex mediates formation of reactive oxygen species and p38 MAPK activation. This is a novel mechanism of redox-sensitive signaling in human endothelial cells.
烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（Nox）复合物是血管壁中活性氧（ROS）形成的主要来源。我们使用DNA微阵列、实时PCR和蛋白质印迹法证明，亚基Nox4是原代人内皮细胞中主要的Nox亚型；我们还发现烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基p22（phox）表达水平很高。通过激光扫描共聚焦显微镜观察到Nox4定位于内皮细胞的细胞质内。内皮细胞中Nox4的过表达增强了超氧阴离子的形成以及p38丝裂原活化蛋白激酶（MAPK）的磷酸化。与转化生长因子-β（TGF-β）相反，通过短发夹RNA（shRNA）下调Nox4对p38 MAPK磷酸化没有影响。我们得出结论，Nox4是人类内皮细胞中主要的Nox亚型，并与p22（phox）形成活性复合物。含Nox4的复合物介导活性氧的形成和p38 MAPK的激活。这是人类内皮细胞中氧化还原敏感信号传导的一种新机制。
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