HYPOXIA INJURES ENDOTHELIAL-CELLS BY INCREASING ENDOGENOUS XANTHINE-OXIDASE ACTIVITY

被引:189
作者
TERADA, LS
GUIDOT, DM
LEFF, JA
WILLINGHAM, IR
HANLEY, ME
PIERMATTEI, D
REPINE, JE
机构
[1] UNIV COLORADO, HLTH SCI CTR, DEPT NEUROSURG, DENVER, CO 80262 USA
[2] UNIV COLORADO, HLTH SCI CTR, DEPT MED, DENVER, CO 80262 USA
关键词
OXYGEN RADICALS; VASCULAR INJURY; LUNG; SUPEROXIDE ANION; NEUTROPHILS;
D O I
10.1073/pnas.89.8.3362
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-.) 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 Cr-51, 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) Cr-51 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.
引用
收藏
页码:3362 / 3366
页数:5
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