Nox4 Is a Major Source of Superoxide Production in Human Brain Pericytes
Abstract
Background Pericytes are multifunctional cells surrounding capillaries and postcapillary venules. In brain microvasculature, pericytes play a pivotal role under physiological and pathological conditions by producing reactive oxygen species (ROS). The aims of this study were to elucidate the source of ROS and its regulation in human brain pericytes. Methods The expression of Nox enzymes in the cells was evaluated using RT-PCR and western blot. Superoxide production was determined by superoxide dismutase-inhibitable chemiluminescence. Silencing of Nox4 was performed using RNAi, and cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Results Nox4 was predominant among the Nox family in human brain pericytes. Membrane fractions of cells produced superoxide in the presence of NAD(P)H. Superoxide production was almost abolished with diphenileneiodonium, a Nox inhibitor; however, inhibitors of other possible superoxide-producing enzymes had no effect on NAD(P)H-dependent superoxide production. Pericytes expressed angiotensin II (Ang II) receptors, and Ang II upregulated Nox4 expression. Hypoxic conditions also increased the Nox4 expression. Silencing of Nox4 significantly reduced ROS production and attenuated cell proliferation. Conclusion Our study showed that Nox4 is a major superoxide-producing enzyme and that its expression is regulated by Ang II and hypoxic stress in human brain pericyt…
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NOX4 is a major source of superoxide production in human brain and promotes neural stem cell growth.
“As a member of the NOX family genes that encode subunits of NADPH oxidase, NOX4 is a major source of superoxide production in human brain and a promoter of neural stem cell growth (Kuroda et al., 2014; Topchiy et al., 2013).”
From Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders (2019) · cites this paper as Kuroda et al., 2014
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“As a member of the NOX family genes that encode subunits of NADPH oxidase, NOX4 is a major source of superoxide production in human brain and a promoter of neural stem cell growth (Kuroda et al., 2014; Topchiy et al., 2013).”
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“As a member of the family of NOX genes that encode subunits of NADPH oxidase, NOX4 is a major source of superoxide production in human brain and a promoter of neural stem cell growth (Kuroda et al., 2014; Topchiy et al., 2013).”
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Amaro, S., Urra, X., & Chamorro, Á. (2017) · Springer series in translational stroke research · doi:10.1007/978-3-319-45345-3_15
- Authors
- Kuroda, J., Ago, T., Nishimura, A., Nakamura, K., Matsuo, R., Wakisaka, Y., Kamouchi, M., & Kitazono, T.
- Affiliations
- Kyushu University (JP)
- ORCID
- Venue
- Journal of Vascular Research
- Publisher
- S. Karger AG
- Published
- 2014
- Volume
- 51
- Issue
- 6
- Pages
- 429-438
- ISSN
- 1018-1172 (ISSN-L)
- 1423-0135
- OpenAlex
- W2011992792
- Cited by
- 73
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 10 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 9 · 2018: 6 · 2017: 10 · 2016: 7 · 2015: 5
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Vascular Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Agricultural Sciences
- Japan Society for the Promotion of Science (25461134, 26462163, 26461145, 26861169)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- NOX4, superoxide production, brain pericytes, reactive oxygen species, angiotensin II receptor, hypoxia, pericyte proliferation, phenytoin, cerebral microvasculature
- MeSH terms
- NADPH Oxidase 4, Angiotensin II, Animals, Brain, Cell Membrane, Cells, Cultured, Disease Models, Animal, Enzyme Inhibitors, Humans, Male, Receptors, Angiotensin, Superoxides, Time Factors, Transfection, Cell Hypoxia, NADPH Oxidases, Infarction, Middle Cerebral Artery, Pericytes, RNA Interference, Cell Proliferation, Mice, Microvessels
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