Cited by 486Redox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative MechanismsNitric Oxide and Endothelin Effects

Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1

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Arnold, Rebecca S., Shi, Jing, Murad, Emma, Whalen, Anne M., Sun, Carrie Q., Polavarapu, Rathnagiri, Parthasarathy, Sampath, Petros, John A. +1 more·2001·Proceedings of the National Academy of Sciences

Abstract

Nox1, a homologue of gp91 phox , the catalytic moiety of the superoxide (O \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{2}^{-}}}\end{equation*}\end{document} )-generating NADPH oxidase of phagocytes, causes increased O \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{2}^{-}}}\end{equation*}\end{document} generation, increased mitotic rate, cell transformation, and tumorigenicity when expressed in NIH 3T3 fibroblasts. This study explores the role of reactive oxygen species (ROS) in regulating cell growth and transformation by Nox1. H 2 O 2 concentration increased ≈10-fold in Nox1-expressing cells, compared with <2-fold increase in O \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{2}^{-}}}\end{equation*}\end{document} . When human catalase was expressed in Nox1-expressing cells, H 2 O 2 concentration decreased, and the cells reverted to a normal appearance, the growth rate normalized, and cells no longer produced tumors in athymic mice. A large number of genes, including many related to cell cycle, growth, and cancer (but unrelated to oxidative stress), were expressed in Nox1-expressing cells, and more than 60% of these returned to normal levels on coexpression of catalase. Thus, H 2 O 2 in low concentrations functions as an intracellular signal that triggers a genetic program related to cell growth.

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Crossref · 10.1073/pnas.101505898

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  • Elevation of reactive metabolites can support oncogenesis in some contexts.

    “While elevation of reactive metabolites can support oncogenesis in some contexts (Arnold et al., 2001; Irani et al., 1997; Suh et al., 1999; Weinberg et al., 2010), at high levels reactive metabolites become toxic and kill cells due to the resulting damage to the proteome and genome (Karisch et al., 2011; Rabbani and Thornalley, 2014).”

    From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Arnold et al., 2001

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Authors
Arnold, R. S., Shi, J., Murad, E., Whalen, A. M., Sun, C. Q., Polavarapu, R., Parthasarathy, S., Petros, J. A., & Lambeth, J. D.
Affiliations
Emory University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2001-05
Volume
98
Issue
10
Pages
5550-5555
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2011993914
Cited by
486
References
50
Citations by year
2026: 4 · 2025: 4 · 2024: 10 · 2023: 12 · 2022: 10 · 2021: 14 · 2020: 15 · 2019: 14 · 2018: 8 · 2017: 24 · 2016: 17 · 2015: 20 · 2014: 11 · 2013: 19 · 2012: 19
FWCI
10.36
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (CA-84138, R01CA084138)
Topics
  • 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
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
NOX1, hydrogen peroxide, reactive oxygen species, NADPH oxidase, cell transformation, cell growth, catalase, superoxide, tumorigenicity, gp91phox, cell cycle genes, gene expression, oxidative stress, NIH3T3 cells, cancer genes, athymic mice
MeSH terms
NADPH Oxidase 1, Animals, Base Sequence, Catalase, Cell Division, Cell Line, Cell Transformation, Neoplastic, Hydrogen Peroxide, Mice, Nude, NADH, NADPH Oxidoreductases, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Mice

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