Novel gp91phox homologues in vascular smooth muscle cells -: Nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways
Novel gp91phox homologues in vascular smooth muscle cells -: Nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways
复制标题
DOI：
10.1161/hh0901.090299
复制
发表时间：
2001-05-11
影响因子：
20.1
通讯作者：
Griendling, KK
中科院分区：
文献类型：
--
作者：
Lassègue, B;Sorescu, D;Griendling, KK
尽管NAD（P）H氧化酶被认为是血管壁中超氧化物的主要来源，但这些蛋白的分子身份仍不清楚。我们最近克隆了nox 1（以前的mox-1），一个新的家族的gp 91（phox）同源物的成员，并表明它是在增殖的血管平滑肌细胞（VSMCs）中表达。在这项研究中，我们检查了三个或非家族成员，nox 1，nox 4和gp 91（phox），在VSMCs中的表达，它们的调节血管紧张素II（Ang II），和它们在氧化还原敏感信号中的作用。我们发现nox 1和nox 4在VSMC中的表达程度比gp 91（phox）高得多。虽然血清，血小板衍生生长因子（PDGF），和血管紧张素LI下调nox 4，他们显着上调nox 1，这表明这种酶可能占这些细胞中的超氧化物产生的延迟阶段。此外，腺病毒表达反义nox 1 mRNA完全抑制早期阶段的超氧化物生成诱导的血管紧张素II或PDGF和显着降低激活氧化还原敏感的信号分子p38丝裂原活化蛋白激酶和Akt的血管紧张素II。相反，PDGF或Ang II诱导的氧化还原非依赖性途径不受影响。这些数据支持nox 1在VSMC氧化还原信号传导中的作用，并提供了对VSMC NAD（P）H氧化酶分子特性及其在血管疾病中潜在关键作用的深入了解。
Emerging evidence indicates that reactive oxygen species are important regulators of vascular function, Although NAD(P)H oxidases have been implicated as major sources of superoxide in the vessel wall, the molecular identity of these proteins remains unclear. We recently cloned nox1 (formerly mox-1), a member of a new family of gp91(phox) homologues, and showed that it is expressed in proliferating vascular smooth muscle cells (VSMCs), In this study, we examined the expression of three nor family members, nox1, nox4, and gp91(phox), in VSMCs, their regulation by angiotensin II (Ang II), and their role in redox-sensitive signaling. We found that both nox1 and nox4 are expressed to a much higher degree than gp91(phox) in VSMCs. Although serum, platelet-derived growth factor (PDGF), and Ang LI downregulated nox4, they markedly upregulated nox1, suggesting that this enzyme may account for the delayed phase of superoxide production in these cells. Furthermore, an adenovirus expressing antisense nox1 mRNA completely inhibited the early phase of superoxide production induced by Ang II or PDGF and significantly decreased activation of the redox-sensitive signaling molecules p38 mitogen-activated protein kinase and Akt by Ang II. In contrast, redox-independent pathways induced by PDGF or Ang II were unaffected, These data support a role for nox1 in redox signaling in VSMCs and provide insight into the molecular identity of the VSMC NAD(P)H oxidase and its potentially critical role in vascular disease.