NADPH oxidase(s): new source(s) of reactive oxygen species in the vascular system?

Overproduction of superoxide anion (•O2−) and O-linked β-N-acetylglucosamine (O-GlcNAc) modification in the vascular system are contributors to endothelial dysfunction. This study tested the hypothesis that increased levels of O-GlcNAc-modified proteins contribute to •O2− production via activation of NADPH oxidase, resulting in impaired vasodilation. Rat aortic segments and vascular smooth muscle cells (VSMCs) were incubated with vehicle (methanol) or O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc) (100 μM). PUGNAc produced a time-dependent increase in O-GlcNAc levels in VSMC and decreased endothelium-dependent relaxation, which was prevented by apocynin and tiron, suggesting that •O2− contributes to endothelial dysfunction under augmented O-GlcNAc levels. Aortic segments incubated with PUGNAc also exhibited increased levels of reactive oxygen species, assessed by dihydroethidium fluorescence, and augmented •O2− production, determined by lucigenin-enhanced chemiluminescence. Additionally, PUGNAc treatment increased Nox-1 and Nox-4 protein expression in aortas and VSMCs. Translocation of the p47phox subunit from the cytosol to the membrane was greater in aortas incubated with PUGNAc. VSMCs displayed increased p22phox protein expression after PUGNAc incubation, suggesting that NADPH oxidase is activated in conditions where O-GlcNAc protein levels are increased. In conclusion, O-GlcNAc levels reduce endothelium-dependent relaxation by overproduction of •O2− via activation of NADPH oxidase. This may represent an additional mechanism by which augmented O-GlcNAc levels impair vascular function.

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Faculty Opinions recommendation of Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.716297801.791652853 ◽

2012 ◽

Author(s):

Martin A Schwartz

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Reactive Oxygen ◽

Oxygen Species

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Thioredoxin-interacting Protein Mediates High Glucose-induced Reactive Oxygen Species Generation by Mitochondria and the NADPH Oxidase, Nox4, in Mesangial Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m112.419101 ◽

2013 ◽

Vol 288 (10) ◽

pp. 6835-6848 ◽

Cited By ~ 95

Author(s):

Anu Shah ◽

Ling Xia ◽

Howard Goldberg ◽

Ken W. Lee ◽

Susan E. Quaggin ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

High Glucose ◽

Mesangial Cells ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Interacting Protein ◽

Thioredoxin Interacting Protein

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Role of NADPH Oxidase-Mediated Reactive Oxygen Species in Podocyte Injury

BioMed Research International ◽

10.1155/2013/839761 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 47

Author(s):

Shan Chen ◽

Xian-Fang Meng ◽

Chun Zhang

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Epithelial To Mesenchymal Transition ◽

Kidney Diseases ◽

Treatment Strategies ◽

Reactive Oxygen ◽

Glomerular Sclerosis ◽

Oxygen Species ◽

Podocyte Injury ◽

Mesenchymal Transition

Proteinuria is an independent risk factor for end-stage renal disease (ESRD) (Shankland, 2006). Recent studies highlighted the mechanisms of podocyte injury and implications for potential treatment strategies in proteinuric kidney diseases (Zhang et al., 2012). Reactive oxygen species (ROS) are cellular signals which are closely associated with the development and progression of glomerular sclerosis. NADPH oxidase is a district enzymatic source of cellular ROS production and prominently expressed in podocytes (Zhang et al., 2010). In the last decade, it has become evident that NADPH oxidase-derived ROS overproduction is a key trigger of podocyte injury, such as renin-angiotensin-aldosterone system activation (Whaley-Connell et al., 2006), epithelial-to-mesenchymal transition (Zhang et al., 2011), and inflammatory priming (Abais et al., 2013). This review focuses on the mechanism of NADPH oxidase-mediated ROS in podocyte injury under different pathophysiological conditions. In addition, we also reviewed the therapeutic perspectives of NADPH oxidase in kidney diseases related to podocyte injury.

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