Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2
Open accessAbstract
In recent years, reactive oxygen species (ROS) derived from the vascular isoforms of NADPH oxidase, Nox1, Nox2, and Nox4, have been implicated in many cardiovascular pathologies. As a result, the selective inhibition of these isoforms is an area of intense current investigation. In this study, we postulated that Nox2ds, a peptidic inhibitor that mimics a sequence in the cytosolic B-loop of Nox2, would inhibit ROS production by the Nox2-, but not the Nox1- and Nox4-oxidase systems. To test our hypothesis, the inhibitory activity of Nox2ds was assessed in cell-free assays using reconstituted systems expressing the Nox2-, canonical or hybrid Nox1-, or Nox4-oxidase. Our findings demonstrate that Nox2ds, but not its scrambled control, potently inhibited superoxide (O(2)(•-)) production in the Nox2 cell-free system, as assessed by the cytochrome c assay. Electron paramagnetic resonance confirmed that Nox2ds inhibits O(2)(•-) production by Nox2 oxidase. In contrast, Nox2ds did not inhibit ROS production by either Nox1- or Nox4-oxidase. These findings demonstrate that Nox2ds is a selective inhibitor of Nox2-oxidase and support its utility to elucidate the role of Nox2 in organ pathophysiology and its potential as a therapeutic agent.
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The inhibitor shows high specificity toward NOX2.
“The inhibitor shows high specificity toward NOX2 (199).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [199]
NOX2 docking sequence-tat (NOX2ds-tat) is the first isoform-specific NOX inhibitor, a peptide based on the sequence of the B-loop of NOX2.
“NOX2 docking sequence-tat (NOX2ds-tat), the first isoform-specific NOX inhibitor, is a peptide based on the sequence of the B-loop of NOX2 (199, 218, 782).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [199]
NOX2ds blocks specifically the interaction between NOX2 and p47phox.
“NOX2ds blocks specifically the interaction between NOX2 and p47phox (199).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [199]
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References 50 · Cited by 131
- Authors
- Csányi, G., Cifuentes-Pagano, E., Al Ghouleh, I., Ranayhossaini, D. J., Egaña, L., Lopes, L. R., Jackson, H. M., Kelley, E. E., & Pagano, P. J.
- Affiliations
- University of Pittsburgh (US)
- Universidade de São Paulo (BR)
- Emory University (US)
- Corresponding author
- Pagano, Patrick J.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 51
- Issue
- 6
- Pages
- 1116-1125
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC3204933
- OpenAlex
- W2009005609
- Cited by
- 131
- References
- 50
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 12 · 2018: 4 · 2017: 10 · 2016: 12 · 2015: 15 · 2014: 17 · 2013: 10 · 2012: 9
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- Hemophilia Center of Western Pennsylvania
- National Institutes of Health
- School of Medicine, Indiana University
- National Heart, Lung, and Blood Institute (R01HL079207, HL 079207, HL55425, R01HL055425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NOX2, NADPH oxidase, peptide inhibitors, superoxide production, reactive oxygen species, NOX1, NOX4, selective enzyme inhibition, cardiovascular disease, electron spin resonance
- MeSH terms
- NADPH Oxidase 2, Animals, Antioxidants, Chlorocebus aethiops, Electron Spin Resonance Spectroscopy, Humans, Membrane Glycoproteins, Peptide Fragments, Superoxides, Protein Engineering, Reactive Oxygen Species, NADPH Oxidases, COS Cells, Biomimetic Materials
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