Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor-alpha in human aortic smooth muscle and embryonic kidney cells.

Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor-alpha in human aortic smooth muscle and embryonic kidney cells.
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DOI:
10.1111/j.1582-4934.2006.tb00304.x
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发表时间:
2006-01
影响因子:
5.3
通讯作者:
Dusting GJ
Dusting GJ
中科院分区:
医学2区
文献类型:
--
作者:
Moe KT;Aulia S;Jiang F;Chua YL;Koh TH;Wong MC;Dusting GJ

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NADPH氧化酶是血管超氧化物的重要来源,与动脉粥样硬化的发病机制有关。以前,我们证明了NADPH氧化酶的Nox 4亚基是一个关键的催化成分,在静止的血管平滑肌细胞超氧化物的生产。在这项研究中,我们试图确定在促炎条件下,Nox 4在人主动脉平滑肌细胞(AoSMC)和胚胎肾(HEK 293)细胞中超氧化物生成中的作用。与肿瘤坏死因子-α(TNF-α,10 ng/ml)孵育12 h可增加两种细胞的超氧化物生成,而血管紧张素II、血小板源性生长因子或白细胞介素-1 β的影响很小。NADPH氧化酶抑制剂diphenyline iodonium和apocynin完全消除了超氧化物的产生,但黄嘌呤氧化酶,一氧化氮合酶或线粒体电子传递的抑制剂。TNF-α可上调AoSMC中Nox 4的表达,但对Nox 1和Nox 2无明显影响。相反,Nox 2的上调似乎介导了HEK 293细胞中TNF-α产生超氧化物的增加。我们认为,Nox 4可能参与增加超氧化物生成血管平滑肌细胞在促炎条件下。
NADPH oxidases are important sources of vascular superoxide, which has been linked to the pathogenesis of atherosclerosis. Previously we demonstrated that the Nox4 subunit of NADPH oxidase is a critical catalytic component for superoxide production in quiescent vascular smooth muscle cells. In this study we sought to determine the role of Nox4 in superoxide production in human aortic smooth muscle cells (AoSMC) and embryonic kidney (HEK293) cells under proinflammatory conditions. Incubation with tumor necrosis factor-α (TNF-α, 10 ng/ml) for 12h increased superoxide production in both cell types, whereas angiotensin II, platelet-derived growth factor or interleukin-1β had little effects. Superoxide production was completely abolished by the NADPH oxidase inhibitors diphenyline iodonium and apocynin, but not by inhibitors of xanthine oxidase, nitric oxide synthase or mitochondrial electron transport. TNF-α upregulated the expression of Nox4 in AoSMC at both message and protein levels, while Nox1 and Nox2 were unchanged. In contrast, upregulation of Nox2 appeared to mediate the enhanced superoxide production by TNF-α in HEK293 cells. We suggest that Nox4 may be involved in increased superoxide generation in vascular smooth muscle cells under proinflammatory conditions.
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发表时间: 2004-03-01
影响因子: --
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发表时间: 2001-05-11
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