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Cited by 275Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

The superoxide‐producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells

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Kuroda, Junya, Nakagawa, Kazunori, Yamasaki, Tomoko, Nakamura, Kei‐ichiro, Takeya, Ryu, Kuribayashi, Futoshi, Imajoh‐Ohmi, Shinobu, Igarashi, Kazuhiko +3 more·2005·Genes to Cells
DOI 10.1111/j.1365-2443.2005.00907.x
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Abstract

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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Crossref · 10.1111/j.1365-2443.2005.00907.x

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  • NOX4 has been reported to be localized within the mitochondrion either constitutively or in specific pathological conditions, although controversial.

    “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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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
DOI
10.1111/j.1365-2443.2005.00907.x
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
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Genes to Cells (publishedVersion)
  • PubMed (publishedVersion)
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 › 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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