Positive regulation of NADPH oxidase 5 by proinflammatory-related mechanisms in human aortic smooth muscle cells

Manea, Adrian; Manea, Simona-Adriana; Florea, Irina C.; Luca, Cătălina; Raicu, Monica

doi:10.1016/j.freeradbiomed.2012.02.018

Cited by 44 publications

(38 citation statements)

References 43 publications

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“…Studies have shown that NOX5 activity and expression is regulated by NF-κB, AP-1, and STAT1/STAT3, and is increased by growth factors including PDGF [52], [85], [86]. NOX5 is thought to be an important regulator of numerous vascular pathologies playing a role in cell proliferation, cell growth, and signal transduction [43], [87].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Intermediate-Conductance Ca2+-Activated K+ Channels (KCNN4) in Porcine Coronary Smooth Muscle Requires NADPH Oxidase 5 (NOX5)

2014

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AimsNADPH oxidase (NOX) is the primary source of reactive oxygen species (ROS) in vascular smooth muscle cells (SMC) and is proposed to play a key role in redox signaling involved in the pathogenesis of cardiovascular disease. Growth factors and cytokines stimulate coronary SMC (CSMC) phenotypic modulation, proliferation, and migration during atherosclerotic plaque development and restenosis. We previously demonstrated that increased expression and activity of intermediate-conductance Ca2+-activated K+ channels (KCNN4) is necessary for CSMC phenotypic modulation and progression of stenotic lesions. Therefore, the purpose of this study was to determine whether NOX is required for KCNN4 upregulation induced by mitogenic growth factors.Methods and ResultsDihydroethidium micro-fluorography in porcine CSMCs demonstrated that basic fibroblast growth factor (bFGF) increased superoxide production, which was blocked by the NOX inhibitor apocynin (Apo). Apo also blocked bFGF-induced increases in KCNN4 mRNA levels in both right coronary artery sections and CSMCs. Similarly, immunohistochemistry and whole cell voltage clamp showed bFGF-induced increases in CSMC KCNN4 protein expression and channel activity were abolished by Apo. Treatment with Apo also inhibited bFGF-induced increases in activator protein-1 promoter activity, as measured by luciferase activity assay. qRT-PCR demonstrated porcine coronary smooth muscle expression of NOX1, NOX2, NOX4, and NOX5 isoforms. Knockdown of NOX5 alone prevented both bFGF-induced upregulation of KCNN4 mRNA and CSMC migration.ConclusionsOur findings provide novel evidence that NOX5-derived ROS increase functional expression of KCNN4 through activator protein-1, providing another potential link between NOX, CSMC phenotypic modulation, and atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Upregulation of Intermediate-Conductance Ca2+-Activated K+ Channels (KCNN4) in Porcine Coronary Smooth Muscle Requires NADPH Oxidase 5 (NOX5)

2014

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“…Vascular Nox5 is activated by PDGF, Ang II, and ET-1 and it involves ERK1/2, PI(4, 5)P2, PKC, and c-Abl (17, 137,155). Hsp90 binds to and regulates Nox5 protein stability (56,126,33). In human endothelial cells (ECs), siRNA-mediated Nox5 knockdown reduced Ang II stimulated ERK1/2 activation, but not that of p38 MAPK or JNK (56 (135,203).…”

Section: Nox5mentioning

confidence: 99%

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

232

177

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Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

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“…Recent cloning of a putative promoter region of NOX5 revealed binding sites for NF-kB, AP-1, and STAT1/STAT3 44 but this region is not likely to encompass all of the regulatory elements or explain cell specific expression in certain cell types. The highest levels of NOX5 expression are observed in the spleen and testis 2 and lower levels are seen in the vasculature, the gastrointestinal tract, fetal organs and various cancers 1, 2, 45 .…”

Section: Functional Significance Of Nox5mentioning

confidence: 99%

“…The highest levels of NOX5 expression are observed in the spleen and testis 2 and lower levels are seen in the vasculature, the gastrointestinal tract, fetal organs and various cancers 1, 2, 45 . Increased NOX5 expression can be triggered by a variety of mechanisms including acid- treatment of esophageal adenocarcinoma cells, thrombin-treatment of endothelial cells 22, 46 and treatment of smooth muscle cells with angiotensin II, endothelin-1 47 , PDGF 48 , TNFα 41 and IFNγ 44 . Epigenetics may have a more profound role in the regulation of NOX5 expression in different cells types.…”

Section: Functional Significance Of Nox5mentioning

confidence: 99%

Enzymatic regulation and functional relevance of NOX5

Chen

Wang²,

Barman³

et al. 2015

CPD

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The NADPH oxidases (NOX) represent a family of 7 related transmembrane enzymes that share a basic structural paradigm and the common ability to utilize NADPH to synthesize superoxide and other reactive oxygen species (ROS). NOX isoforms are distinguished from each other by their amino acid sequences, expression levels in different cell types, the mechanisms of enzyme activation and the type of ROS that are generated. NOX5 was the last NOX family member to be identified and in the past decade and a half we have gained significant insights into how NOX5 produces ROS, the cell types where it is expressed and the functional significance of NOX5 in health and disease. The objective of this review is to highlight accumulated and recent knowledge of the genetic and enzymatic regulation of NOX5 and the importance of NOX5 in human physiology and pathophysiology.

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Positive regulation of NADPH oxidase 5 by proinflammatory-related mechanisms in human aortic smooth muscle cells

Cited by 44 publications

References 43 publications

Upregulation of Intermediate-Conductance Ca2+-Activated K+ Channels (KCNN4) in Porcine Coronary Smooth Muscle Requires NADPH Oxidase 5 (NOX5)

Upregulation of Intermediate-Conductance Ca2+-Activated K+ Channels (KCNN4) in Porcine Coronary Smooth Muscle Requires NADPH Oxidase 5 (NOX5)

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Enzymatic regulation and functional relevance of NOX5

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