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

doi:10.1073/pnas.89.8.3362

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 journal › Article › peer-review

183 Scopus citations

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 language	English (US)
Pages (from-to)	3362-3366
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	89
Issue number	8
DOIs	https://doi.org/10.1073/pnas.89.8.3362
State	Published - 1992

Keywords

Lung
Neutrophils
Oxygen radicals
Superoxide anion
Vascular injury

ASJC Scopus subject areas

General

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10.1073/pnas.89.8.3362

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title = "Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity",

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.",

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author = "Terada, {Lance S.} and Guidot, {David M.} and Leff, {Jonathan A.} and Willingham, {Irene R.} and Hanley, {Michael E.} and Dale Piermattei and Repine, {John E.}",

year = "1992",

doi = "10.1073/pnas.89.8.3362",

language = "English (US)",

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AU - Terada, Lance S.

AU - Guidot, David M.

AU - Leff, Jonathan A.

AU - Willingham, Irene R.

AU - Hanley, Michael E.

AU - Piermattei, Dale

AU - Repine, John E.

PY - 1992

Y1 - 1992

N2 - 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.

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.

KW - Lung

KW - Neutrophils

KW - Oxygen radicals

KW - Superoxide anion

KW - Vascular injury

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Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity

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