Cited by 142Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressNitric Oxide and Endothelin Effects

Nitric Oxide Inactivates NADPH Oxidase in Pig Neutrophils by Inhibiting Its Assembling Process

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Fujii, Hirotada, Ichimori, Kohji, Hoshiai, Kiyotaka, Nakazawa, Hiroe·1997·Journal of Biological Chemistry

Abstract

The effects of nitric oxide (NO) on superoxide (O-2) generation of the NADPH oxidase in pig neutrophils were studied. NO dose-dependently suppressed O-2 generation of both neutrophil NADPH oxidase and reconstituted NADPH oxidase. Effects of NO on NADPH-binding site and the redox centers including FAD and low spin heme in cytochrome b558 and the electron transfer rates from NADPH to heme via FAD were examined under anaerobic conditions. Both reaction rates and the Km value for NADPH were unchanged by NO. Visible and EPR spectra of cytochrome b558 showed that the structure of heme was unchanged by NO, indicating that NO does not affect the redox centers of the oxidase. In reconstituted NADPH oxidase system, NO did not inhibit O-2 generation of the oxidase when added after activation. The addition of NO to the membrane component or the cytosol component inhibited the activity by 24.0 +/- 5.3 or 37.4 +/- 7.1%, respectively. The addition of NO during the activation process or to the cytosol component simultaneously with myristate inhibited the activity by 74.0 +/- 5.2 or 70.0 +/- 8.3%, respectively, suggesting that cytosol protein(s) treated with myristate becomes susceptible to NO. Peroxynitrite did not interfere with O-2 generation.

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Crossref · 10.1074/jbc.272.52.32773

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  • NO, through its high affinity for heme groups or via S-nitrosation, can act as an important modulator of NOX or can modulate the insertion of heme in the receptor sGC.

    “In another example, NO, through its high affinity for heme groups or via S-nitrosation, can act as an important modulator of NOX (176, 315, 846) or can also modulate the insertion of heme in the receptor sGC.”

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Authors
Fujii, H., Ichimori, K., Hoshiai, K., & Nakazawa, H.
Affiliations
  • Tokyo Metropolitan Institute of Medical Science (JP)
  • Tokai University (JP)
Corresponding author
Fujii, Hirotada
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-12
Volume
272
Issue
52
Pages
32773-32778
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2053018171
Cited by
142
References
32
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 3
FWCI
3.64
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Ohio State University
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
nitric oxide, NADPH oxidase, neutrophils, superoxide production, cytochrome b558, FAD, low-spin heme, myristate, peroxynitrite
MeSH terms
Animals, Cytochrome b Group, Electron Spin Resonance Spectroscopy, Flavin-Adenine Dinucleotide, Kinetics, NADP, Neutrophils, Nitrates, Nitric Oxide, Spectrophotometry, Atomic, Superoxides, Swine, Protein Folding, NADPH Oxidases, Myristic Acid

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