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The superoxide‐producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells
Open accessAbstract
The superoxide‐producing NAD(P)H oxidase Nox4 was initially identified as an enzyme that is highly expressed in the kidney and is possibly involved in oxygen sensing and cellular senescence. Although the oxidase is also abundant in vascular endothelial cells, its role remains to be elucidated. Here we show that Nox4 preferentially localizes to the nucleus of human umbilical vein endothelial cells (HUVECs), by immunocytochemistry and immunoelectron microscopy using three kinds of affinity‐purified antibodies raised against distinct immunogens from human Nox4. Silencing of Nox4 by RNA interference (RNAi) abrogates nuclear signals given with the antibodies, confirming the nuclear localization of Nox4. The nuclear fraction of HUVECs exhibits an NAD(P)H‐dependent superoxide‐producing activity in a manner dependent on Nox4, which activity can be enhanced upon cell stimulation with phorbol 12‐myristate 13‐acetate. This stimulant also facilitates gene expression as estimated in the present transfection assay of HUVECs using a reporter regulated by the Maf‐recognition element MARE, a DNA sequence that constitutes a part of oxidative stress response. Both basal and stimulated transcriptional activities are impaired by RNAi‐mediated Nox4 silencing. Thus Nox4 appears to produce superoxide in the nucleus of HUVECs, thereby regulating gene expression via a mechanism for oxidative stress response.
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“Additionally, although controversial, NOX4 has been reported to be localized within the mitochondrion either constitutively or in specific pathological conditions (152, 306, 540).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [540]
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Metadata
- Authors
- Kuroda, J., Nakagawa, K., Yamasaki, T., Nakamura, K., Takeya, R., Kuribayashi, F., Imajoh‐Ohmi, S., Igarashi, K., Shibata, Y., Sueishi, K., & Sumimoto, H.
- Affiliations
- Kyushu University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Hiroshima University (JP)
- Corresponding author
- Sumimoto, Hideki
- ORCID
- Venue
- Genes to Cells
- Publisher
- Wiley
- Published
- 2005-10-26
- Volume
- 10
- Issue
- 12
- Pages
- 1139-1151
- ISSN
- 1356-9597 (ISSN-L)
- 1365-2443
- OpenAlex
- W2168243468
- Cited by
- 275
- References
- 47
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 4 · 2021: 8 · 2020: 17 · 2019: 14 · 2018: 10 · 2017: 17 · 2016: 14 · 2015: 16 · 2014: 13 · 2013: 23 · 2012: 15
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes to Cells (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NOX4, NADPH oxidase, superoxide, nuclear localization, vascular endothelial cells, human umbilical vein endothelial cells, oxidative stress response, mares, transcriptional regulation, phorbol myristate acetate, RNA interference
- MeSH terms
- NADPH Oxidase 4, Base Sequence, Cell Nucleus, Cells, Cultured, Gene Expression Regulation, Humans, Phosphoproteins, Tetradecanoylphorbol Acetate, Umbilical Veins, Transcriptional Activation, Up-Regulation, Oxidative Stress, NADPH Oxidases, Gene Silencing, Membrane Transport Proteins, RNA Interference, Endothelial Cells, Maf Transcription Factors
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