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Cited by 94Gout, Hyperuricemia, Uric AcidNitric Oxide and Endothelin EffectsRedox biology and oxidative stress

Moderate hypoxia induces xanthine oxidoreductase activity in arterial endothelial cells

Kelley, Eric E., Hock, Thomas, Khoo, Nicholas K.H., Richardson, Gloria R., Johnson, Kamorris K., Powell, Pamela C., Giles, Gregory I., Agarwal, Anupam +2 more·2006·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2005.11.008
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Abstract

Xanthine oxidoreductase (XOR) activity has been previously noted to be responsive to changes in O2 tension. While prior studies have focused on the extremes (0-3% and 95-100%) of O2 tensions, we report the influence of 10% O2 on endothelial cell XOR, a concentration resembling modest arterial hypoxia commonly found in patients with chronic cardiopulmonary diseases. Exposure of bovine aortic endothelial cells to 10% O2 increased XOR mRNA and protein abundance by 50%. Concomitantly, there was a 3-fold increase in XOR activity, XOR-dependent reactive oxygen species production, and cellular export of active enzyme. Although increases in mRNA and immunoreactive protein levels were observed, inhibition of transcription, translation, or protein degradation did not significantly alter cellular XOR specific activity, suggesting only modest contributions to 10% O2-induced effects. Exposure to 10% O2 did not increase cellular HIF-1alpha protein levels and hypoxia mimics did not alter XOR activity. Treatment of control cells with adenosine resulted in increased XOR activity similar to hypoxia. Exposure to the adenosine receptor agonist NECA increased enzymatic activity 4-fold while 8SPT, an adenosine receptor antagonist, reduced hypoxic induction of XOR activity approximately 50%. Combined, these data reveal that moderate hypoxia significantly enhances endothelial XOR specific activity, release, and XOR-derived reactive oxygen species generation. These effects appear to be mediated in part via adenosine-dependent processes.

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Crossref · 10.1016/j.freeradbiomed.2005.11.008

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  • XO catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid, generating hydrogen peroxide and superoxide in a reaction amplified under ischemia and hypoxia.

    “Thus, XO catalyzes the oxidation of hypoxanthine to xanthine and subsequently xanthine to uric acid, generating hydrogen peroxide and superoxide in a reaction amplified under ischemia and hypoxia (147, 307, 496, 497, 499).”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [496]

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Authors
Kelley, E. E., Hock, T., Khoo, N. K. H., Richardson, G. R., Johnson, K. K., Powell, P. C., Giles, G. I., Agarwal, A., Lancaster, J. R., & Tarpey, M. M.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
Kelley, Eric E.
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2006-03
Volume
40
Issue
6
Pages
952-959
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2005.11.008
OpenAlex
W2027609640
Cited by
93
References
35
Citations by year
2026: 5 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 8 · 2014: 6 · 2013: 5 · 2012: 2
FWCI
1.59
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl066110-04)
  • National Heart, Lung, and Blood Institute (R01 HL-66110, R01HL068157, R01HL074391)
Topics
  • Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
xanthine oxidoreductase, moderate hypoxia, arterial endothelial cells, adenosine, adenosine receptors, reactive oxygen species, HIF-1α, chronic cardiopulmonary disease, oxygen partial pressure
MeSH terms
Adenine, Adenosine, Animals, Hypoxia, Aorta, Cattle, Endothelium, Vascular, Enzyme Induction, Oxygen, Xanthine Oxidase, Reactive Oxygen Species, Adenosine-5'-(N-ethylcarboxamide), Hypoxia-Inducible Factor 1, alpha Subunit, Purinergic P1 Receptor Antagonists

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