p40phox as an alternative organizer to p47phox in Nox2 activation: A new mechanism involving an interaction with p22phox

Tamura, Minoru; Shiozaki, Iichiro; Ono, Shohei; Miyano, Kei; Kunihiro, Sachio; Sasaki, Takayuki

doi:10.1016/j.febslet.2007.08.040

Cited by 14 publications

(8 citation statements)

References 22 publications

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“…23 This region also binds p40 phox , which activates Nox2 and completes for p47 phox binding. 24 Moreover, p22 phox associates with and stabilizes the Nox2 during processing and transport to the cell membrane. 25 A similar role for Nox1 likely exists, in that we previously found overexpression of p22 phox in transgenic mice markedly increased Nox1 expression.…”

Section: Discussionmentioning

confidence: 99%

Role of the NADPH Oxidases in the Subfornical Organ in Angiotensin II–Induced Hypertension

et al. 2013

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Reactive oxygen species (ROS) and the NADPH oxidases contribute to hypertension via mechanisms that remain undefined. ROS produced in the central nervous system have been proposed to promote sympathetic outflow, inflammation and hypertension, but the contribution of the NADPH oxidases to these processes in chronic hypertension is uncertain. We therefore sought to identify how NADPH oxidases in the subfornical organ (SFO) of the brain regulate blood pressure and vascular inflammation during sustained hypertension. We produced mice with loxP sites flanking the coding region of the NADPH oxidase docking subunit p22phox. SFO-targeted injections of an adenovirus encoding cre-recombinase (AdCre) markedly diminished p22phox, Nox2 and Nox4 mRNA in the SFO as compared to a control adenovirus (AdRFP) injection. Increased superoxide production in the SFO by chronic angiotensin II infusion (490 ng/kg/min × 2 weeks), was blunted in AdCre-treated mice as detected by dihydroethidium fluorescence. Deletion of p22phox in the SFO eliminated the hypertensive response observed at two weeks of angiotensin II infusion compared to AdRFP-treated mice (mean arterial pressures = 97±15 vs. 154±6 mmHg respectively, p = 0.0001). Angiotensin II-infusion also promoted marked vascular inflammation, as characterized by accumulation of activated T cells and other leukocytes, and this was prevented by deletion of the SFO p22phox. These experiments definitively identify the NADPH oxidases in the SFO as a critical determinant of the blood pressure and vascular inflammatory responses to chronic angiotensin II, and further support a role of ROS in central nervous system signaling in hypertension.

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Section: Discussionmentioning

confidence: 99%

Role of the NADPH Oxidases in the Subfornical Organ in Angiotensin II–Induced Hypertension

et al. 2013

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“…FAD, flavin adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate. the most recently discovered subunit p40phox appears to be modulatory, rather than obligatory, though it constantly associates with p67phox and interacts with p47phox, at least in the resting state (8,29,149). Together, the assembly of this complex forms the functional NOX2 enzyme.…”

Section: Fig 2 Schematic Illustrationmentioning

confidence: 99%

NOX Modifiers—Just a Step Away from Application in the Therapy of Airway Inflammation?

Wieczfińska

Sokołowska

Pawliczak

2015

Antioxidants & Redox Signaling

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Significance: NADPH oxidase (NOX) enzymes, which are widely expressed in different airway cell types, not only contribute to the maintenance of physiological processes in the airways but also participate in the pathogenesis of many acute and chronic diseases. Therefore, the understanding of NOX isoform regulation, expression, and the manner of their potent inhibition might lead to effective therapeutic approaches. Recent Advances: The study of the role of NADPH oxidases family in airway physiology and pathophysiology should be considered as a work in progress. While key questions still remain unresolved, there is significant progress in terms of our understanding of NOX importance in airway diseases as well as a more efficient way of using NOX modifiers in human settings. Critical Issues: Agents that modify the activity of NADPH enzyme components would be considered useful tools in the treatment of various airway diseases. Nevertheless, profound knowledge of airway pathology, as well as the mechanisms of NOX regulation is needed to develop potent but safe NOX modifiers. Future Directions: Many compounds seem to be promising candidates for development into useful therapeutic agents, but their clinical potential is yet to be demonstrated. Further analysis of basic mechanisms in human settings, high-throughput compound scanning, clinical trials with new and existing molecules, and the development of new drug delivery approaches are the main directions of future studies on NOX modifiers. In this article, we discuss the current knowledge with regard to NOX isoform expression and regulation in airway inflammatory diseases as well as the aptitudes and therapeutic potential of NOX modifiers. Antioxid. Redox Signal. 23,[428][429][430][431][432][433][434][435][436][437][438][439][440][441][442][443][444][445]

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“…activation (Tamura et al, 2007), although the relevance of this direct p40phox-p22phox interaction on oxidase activation is still unknown.…”

Section: Molecular Description Of Nadph Oxidasesmentioning

confidence: 99%

NADPH Oxidases as Novel Pharmacologic Targets against Influenza A Virus Infection

Vlahos¹,

Selemidis²

2014

Mol Pharmacol

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Influenza A viruses represent a major global health care challenge, with imminent pandemics, emerging antiviral resistance, and long lag times for vaccine development, raising a pressing need for novel pharmacologic strategies that ideally target the pathology irrespective of the infecting strain. Reactive oxygen species (ROS) pervade all facets of cell biology with both detrimental and protective properties. Indeed, there is compelling evidence that activation of the NADPH oxidase 2 (NOX2) isoform of the NADPH oxidase family of ROS-producing enzymes promotes lung oxidative stress, inflammation, injury, and dysfunction resulting from influenza A viruses of low to high pathogenicity, as well as impeding virus clearance. By contrast, the dual oxidase isoforms produce ROS that provide vital protective antiviral effects for the host. In this review, we propose that inhibitors of NOX2 are better alternatives than broad-spectrum antioxidant approaches for treatment of influenza pathologies, for which clinical efficacy may have been limited owing to poor bioavailability and inadvertent removal of beneficial ROS. Finally, we briefly describe the current suite of NADPH oxidase inhibitors and the molecular features of the NADPH oxidase enzymes that could be exploited by drug discovery for development of more specific and novel inhibitors to prevent or treat disease caused by influenza.

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p40^phox as an alternative organizer to p47^phox in Nox2 activation: A new mechanism involving an interaction with p22^phox

Cited by 14 publications

References 22 publications

Role of the NADPH Oxidases in the Subfornical Organ in Angiotensin II–Induced Hypertension

Role of the NADPH Oxidases in the Subfornical Organ in Angiotensin II–Induced Hypertension

NOX Modifiers—Just a Step Away from Application in the Therapy of Airway Inflammation?

NADPH Oxidases as Novel Pharmacologic Targets against Influenza A Virus Infection

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