HYPOXIA INJURES ENDOTHELIAL-CELLS BY INCREASING ENDOGENOUS XANTHINE-OXIDASE ACTIVITY
HYPOXIA INJURES ENDOTHELIAL-CELLS BY INCREASING ENDOGENOUS XANTHINE-OXIDASE ACTIVITY
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DOI：
10.1073/pnas.89.8.3362
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发表时间：
1992-04-15
影响因子：
11.1
通讯作者：
REPINE, JE
中科院分区：
文献类型：
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作者：
TERADA, LS;GUIDOT, DM;REPINE, JE
在培养的肺动脉内皮细胞（EC）中，暴露于降低氧张力48小时内，黄嘌呤脱氢酶（XD）和黄嘌呤氧化酶（XO）活性逐渐增加，而XD/XO比值没有改变。缺氧诱导的EC中XD和XO活性的增加与再氧化后细胞外超氧阴离子（O2-）水平的升高（P < 0.05）相关，而XO抑制剂（钨、别嘌呤醇）或阴离子通道阻滞剂（4,4'-二异硫氰酸二苯乙烯-2,2'-二磺酸）可以抑制这种水平。缺氧/再氧化的EC单层也比对照单层泄漏了更多的预载Cr-51，更粘附中性粒细胞，并允许更多的白蛋白运输。钨、别嘌呤醇和/或超氧化物歧化酶处理降低（P < 0.05） Cr-51释放、中性粒细胞粘附和暴露于缺氧/再氧化的EC单层中白蛋白转运。我们的结论是，长时间的缺氧增加了EC中XO和XD的活性，并可能使内皮容易受到氧化和炎症损伤。
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.