Nox4 as the Major Catalytic Component of an Endothelial NAD(P)H Oxidase
Abstract
Background— Recent evidence has suggested that reactive oxygen species are important signaling molecules in vascular cells and play a pivotal role in the development of vascular diseases. The activity of NAD(P)H oxidase has been identified as the major source of reactive oxygen species in vascular endothelial cells. However, the precise molecular structure and the mechanism of activation of the oxidase have remained poorly understood. Methods and Results— Here, we investigated the molecular identities and the superoxide-producing activity of endothelial NAD(P)H oxidase. We found that Nox4, a homologue of gp91phox/Nox2, was abundantly expressed in endothelial cells. The expression of Nox4 in endothelial cells markedly exceeded that of other Nox proteins, including gp91phox/Nox2, and was affected by cell growth. Using electron spin resonance and chemiluminescence, we measured the superoxide production and found that the endothelial membranes had an NAD(P)H-dependent superoxide-producing activity comparable to that of the neutrophil membranes, whereas the activity was not enhanced by the 2 recombinant proteins p47phox and p67phox, in contrast to that of the neutrophil membranes. Downregulation of Nox4 by an antisense oligonucleotide reduced superoxide production in endothelial cells in vivo and in vitro. Conclusions— These findings suggest that Nox4 may function as the major catalytic component of an endothelial NAD(P)H oxidase.
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NOX4 is the most abundant isoform in ECs, and it is also present in VSMCs and adventitial fibroblasts.
“NOX4 is the most abundant isoform in ECs, and it is also present in VSMCs and adventitial fibroblasts (10, 265, 736, 832, 876, 1036).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [10]
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- Authors
- Ago, T., Kitazono, T., Ooboshi, H., Iyama, T., Han, Y. H., Takada, J., Wakisaka, M., Ibayashi, S., Utsumi, H., & Iida, M.
- Affiliations
- Kyushu University (JP)
- Venue
- Circulation
- Published
- 2004-01-20
- Volume
- 109
- Issue
- 2
- Pages
- 227-233
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2071919212
- Cited by
- 497
- References
- 29
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 12 · 2022: 17 · 2021: 9 · 2020: 9 · 2019: 16 · 2018: 11 · 2017: 24 · 2016: 16 · 2015: 21 · 2014: 38 · 2013: 25 · 2012: 31
- FWCI
- 24.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- 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
- Keywords
- NOX4, NADPH oxidase, endothelial cells, superoxide production, reactive oxygen species, p47phox, p67phox, oxidative stress signaling, vascular endothelium
- MeSH terms
- NADPH Oxidase 4, Animals, Catalysis, Cell Membrane, Cells, Cultured, Endothelium, Vascular, Gene Expression Regulation, Humans, Male, Phosphoproteins, RNA, Messenger, Superoxides, Rats, Sprague-Dawley, NADPH Oxidases, Protein Subunits, Rats
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