NADPH Oxidases: Physiology and Therapeutic Potential

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Antioxidant Enzyme Systems".

Deadline for manuscript submissions: 30 May 2024 | Viewed by 4760

Special Issue Editors

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131, Naples, Italy
Interests: redox signaling; NOX; GPCRs; TKRs; cellular metabolism
Special Issues, Collections and Topics in MDPI journals
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
Interests: signal transduction; ROS; formyl peptide receptors; NADPH oxidase; TKR-transactivation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

NADPH oxidases (NOXs) belong to a family of evolutionarily conserved enzymes, whose only known function is ROS production. Members of the NOX family are expressed in several cells and tissues, and growing evidence shows that NOX-dependent production of ROS is implicated in biosignaling and cell functions. NOX-mediated redox imbalance and NOX-impaired expression are involved in many physiological and pathological processes, such as cardiovascular, pulmonary, renal and neuronal diseases, as well as cancer. Therefore, NOXs represent a promising target for the development of more effective therapeutic strategies

As guest editors, we invite you to contribute to this Special Issue, entitled “NADPH Oxidases: Physiology and Therapeutic Potential”, with original research articles, clinical reports and review articles that highlight the function of the various members of the NOX family in pathophysiology and their potential role as pharmacological targets.

Prof. Dr. Rosario Ammendola
Dr. Fabio Cattaneo
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • NADPH oxidase
  • NOX
  • ROS
  • redox signaling
  • cancer
  • metabolism
  • inflammation

Published Papers (3 papers)

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Research

16 pages, 2375 KiB  
Article
Formyl Peptide Receptor 2-Dependent cPLA2 and 5-LOX Activation Requires a Functional NADPH Oxidase
by Tiziana Pecchillo Cimmino, Iolanda Panico, Simona Scarano, Mariano Stornaiuolo, Gabriella Esposito, Rosario Ammendola and Fabio Cattaneo
Antioxidants 2024, 13(2), 220; https://doi.org/10.3390/antiox13020220 - 08 Feb 2024
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Abstract
Phospholipases (PL) A2 catalyzes the hydrolysis of membrane phospholipids and mostly generates arachidonic acid (AA). The enzyme 5-lipoxygenase (5-LOX) can metabolize AA to obtain inflammatory leukotrienes, whose biosynthesis highly depends on cPLA2 and 5-LOX activities. Formyl Peptide Receptor 2 (FPR2) belongs to [...] Read more.
Phospholipases (PL) A2 catalyzes the hydrolysis of membrane phospholipids and mostly generates arachidonic acid (AA). The enzyme 5-lipoxygenase (5-LOX) can metabolize AA to obtain inflammatory leukotrienes, whose biosynthesis highly depends on cPLA2 and 5-LOX activities. Formyl Peptide Receptor 2 (FPR2) belongs to a subfamily of class A GPCRs and is considered the most versatile FPRs isoform. Signaling triggered by FPR2 includes the activation of several downstream kinases and NADPH oxidase (NOX)-dependent ROS generation. In a metabolomic analysis we observed a significant increase in AA concentration in FPR2-stimulated lung cancer cell line CaLu-6. We analyzed cPLA2 phosphorylation and observed a time-dependent increase in cPLA2 Ser505 phosphorylation in FPR2-stimulated cells, which was prevented by the MEK inhibitor (PD098059) and the p38MAPK inhibitor (SB203580) and by blocking NOX function. Similarly, we demonstrated that phosphorylation of 5-LOX at Ser271 and Ser663 residues requires FPR2-dependent p38MAPK and ERKs activation. Moreover, we showed that 5-LOX Ser271 phosphorylation depends on a functional NOX expression. Our overall data demonstrate for the first time that FPR2-induced ERK- and p38MAPK-dependent phosphorylation/activation of cPLA2 and 5-LOX requires a functional NADPH oxidase. These findings represent an important step towards future novel therapeutic possibilities aimed at resolving the inflammatory processes underlying many human diseases. Full article
(This article belongs to the Special Issue NADPH Oxidases: Physiology and Therapeutic Potential)
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22 pages, 3594 KiB  
Article
New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22phox-p47phox Interactions
by Adriana V. Treuer, Mario Faúndez, Roberto Ebensperger, Erwin Hovelmeyer, Ariela Vergara-Jaque, Yunier Perera-Sardiña, Margarita Gutierrez, Roberto Fuentealba and Daniel R. González
Antioxidants 2023, 12(7), 1441; https://doi.org/10.3390/antiox12071441 - 18 Jul 2023
Cited by 1 | Viewed by 1442
Abstract
NADPH oxidase (NOX2) is responsible for reactive oxygen species (ROS) production in neutrophils and has been recognized as a key mediator in inflammatory and cardiovascular pathologies. Nevertheless, there is a lack of specific NOX2 pharmacological inhibitors. In medicinal chemistry, heterocyclic compounds are essential [...] Read more.
NADPH oxidase (NOX2) is responsible for reactive oxygen species (ROS) production in neutrophils and has been recognized as a key mediator in inflammatory and cardiovascular pathologies. Nevertheless, there is a lack of specific NOX2 pharmacological inhibitors. In medicinal chemistry, heterocyclic compounds are essential scaffolds for drug design, and among them, indole is a very versatile pharmacophore. We tested the hypothesis that indole heteroaryl-acrylonitrile derivatives may serve as NOX2 inhibitors by evaluating the capacity of 19 of these molecules to inhibit NOX2-derived ROS production in human neutrophils (HL-60 cells). Of these compounds, C6 and C14 exhibited concentration-dependent inhibition of NOX2 (IC50~1 µM). These molecules also reduced NOX2-derived oxidative stress in cardiomyocytes and prevented cardiac damage induced by ischemia-reperfusion. Compound C6 significantly reduced the membrane translocation of p47phox, a cytosolic subunit that is required for NOX2 activation. Molecular docking analyses of the binding modes of these molecules with p47phox indicated that C6 and C14 interact with specific residues in the inner part of the groove of p47phox, the binding cavity for p22phox. This combination of methods showed that novel indole heteroaryl acrylonitriles represent interesting lead compounds for developing specific and potent NOX2 inhibitors. Full article
(This article belongs to the Special Issue NADPH Oxidases: Physiology and Therapeutic Potential)
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16 pages, 2951 KiB  
Article
The NADPH Oxidase Inhibitors Apocynin and Diphenyleneiodonium Protect Rats from LPS-Induced Pulmonary Inflammation
by Ahmed Kouki, Wafa Ferjani, Néziha Ghanem-Boughanmi, Mossadok Ben-Attia, Pham My-Chan Dang, Abdelaziz Souli and Jamel El-Benna
Antioxidants 2023, 12(3), 770; https://doi.org/10.3390/antiox12030770 - 21 Mar 2023
Cited by 4 | Viewed by 1911
Abstract
Inflammation is the body’s response to insults, for instance, lung inflammation is generally caused by pathogens or by exposure to pollutants, irritants and toxins. This process involves many inflammatory cells such as epithelial cells, monocytes, macrophages and neutrophils. These cells produce and release [...] Read more.
Inflammation is the body’s response to insults, for instance, lung inflammation is generally caused by pathogens or by exposure to pollutants, irritants and toxins. This process involves many inflammatory cells such as epithelial cells, monocytes, macrophages and neutrophils. These cells produce and release inflammatory mediators such as pro-inflammatory cytokines, lipids and reactive oxygen species (ROS). Lung epithelial cells and phagocytes (monocytes, macrophages and neutrophils) produce ROS mainly by the NADPH oxidase NOX1 and NOX2, respectively. The aim of this study was to investigate the effects of two NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI), on lipopolysaccharide (LPS)-induced lung inflammation in rats. Our results showed that apocynin and DPI attenuated the LPS-induced morphological and histological alterations of the lung, reduced edema and decreased lung permeability. The evaluation of oxidative stress markers in lung homogenates showed that apocynin and DPI inhibited LPS-induced NADPH oxidase activity, and restored superoxide dismutase (SOD) and catalase activity in the lung resulting in the reduction in LPS-induced protein and lipid oxidation. Additionally, apocynin and DPI decreased LPS-induced MPO activity in bronchoalveolar liquid and lung homogenates, TNF-α and IL-1β in rat plasma. NADPH oxidase inhibition could be a new therapeutic strategy for the treatment of inflammatory lung diseases. Full article
(This article belongs to the Special Issue NADPH Oxidases: Physiology and Therapeutic Potential)
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