Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity

Lance S. Terada, David M. Guidot, Jonathan A. Leff, Irene R. Willingham, Michael E. Hanley, Dale Piermattei, John E. Repine

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Exposure to decreasing oxygen tensions progressively increased xanthine dehydrogenase (XD) and xanthine oxidase (XO) activities over 48 hr in cultured pulmonary artery endothelial cells (EC) without altering XD/XO ratios. Increases in XD and XO activity in EC induced by hypoxia were associated upon reoxygenation with increased (P < 0.05) extracellular superoxide anion (O2 -3) levels that were inhibited by treatment with XO inhibitors (tungsten, allopurinol) or an anion-channel blocker (4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid). EC monolayers subjected to hypoxia/reoxygenation also leaked more preloaded 51Cr, were more adherent to neutrophils, and permitted greater albumin transit than control monolayers. Treatment with tungsten, allopurinol, and/or superoxide dismutase decreased (P < 0.05) 51Cr release, neutrophil adherence, and albumin transit in EC monolayers exposed to hypoxia/reoxygenation. We conclude that prolonged hypoxia increases both XO and XD activity in EC and may predispose the endothelium to oxidative and inflammatory damage.

Original languageEnglish (US)
Pages (from-to)3362-3366
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number8
StatePublished - 1992

Fingerprint

Xanthine Oxidase
Xanthine Dehydrogenase
Endothelial Cells
Allopurinol
Tungsten
Albumins
Neutrophils
Cell Hypoxia
Superoxides
Pulmonary Artery
Superoxide Dismutase
Endothelium
Anions
Hypoxia
Oxygen
Acids

Keywords

  • Lung
  • Neutrophils
  • Oxygen radicals
  • Superoxide anion
  • Vascular injury

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Terada, L. S., Guidot, D. M., Leff, J. A., Willingham, I. R., Hanley, M. E., Piermattei, D., & Repine, J. E. (1992). Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity. Proceedings of the National Academy of Sciences of the United States of America, 89(8), 3362-3366.

Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity. / Terada, Lance S.; Guidot, David M.; Leff, Jonathan A.; Willingham, Irene R.; Hanley, Michael E.; Piermattei, Dale; Repine, John E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 8, 1992, p. 3362-3366.

Research output: Contribution to journalArticle

Terada, LS, Guidot, DM, Leff, JA, Willingham, IR, Hanley, ME, Piermattei, D & Repine, JE 1992, 'Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 8, pp. 3362-3366.
Terada, Lance S. ; Guidot, David M. ; Leff, Jonathan A. ; Willingham, Irene R. ; Hanley, Michael E. ; Piermattei, Dale ; Repine, John E. / Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 8. pp. 3362-3366.
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AB - Exposure to decreasing oxygen tensions progressively increased xanthine dehydrogenase (XD) and xanthine oxidase (XO) activities over 48 hr in cultured pulmonary artery endothelial cells (EC) without altering XD/XO ratios. Increases in XD and XO activity in EC induced by hypoxia were associated upon reoxygenation with increased (P < 0.05) extracellular superoxide anion (O2 -3) levels that were inhibited by treatment with XO inhibitors (tungsten, allopurinol) or an anion-channel blocker (4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid). EC monolayers subjected to hypoxia/reoxygenation also leaked more preloaded 51Cr, were more adherent to neutrophils, and permitted greater albumin transit than control monolayers. Treatment with tungsten, allopurinol, and/or superoxide dismutase decreased (P < 0.05) 51Cr release, neutrophil adherence, and albumin transit in EC monolayers exposed to hypoxia/reoxygenation. We conclude that prolonged hypoxia increases both XO and XD activity in EC and may predispose the endothelium to oxidative and inflammatory damage.

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