Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In animals the terminal step in the pathway for degradation of sulphur-containing amino acids is the oxidation of sulphite to sulphate. This reaction is catalysed by the enzyme sulphite oxidase. The enzyme contains molybdenum and a cytochrome b5 type haem, is localized in the mitochondrial intermembrane space and transfers electrons from sulphite to cytochrome c on the inner membrane. The sulphite oxidase protein has a molecular weight of 110 000 (chicken) to 122 000 (human) and exists as a dimer of identical subunits. The haem and molybdenum cofactors are present on separate domains of the molecule. The structure of the molydbenum cofactor has not been worked out in detail, but this cofactor is known to be present in many other molybdoenzymes including xanthine oxidase and nitrate reductase. Three cases of genetic sulphite oxidase deficiency in humans have been reported. The three affected children displayed mental retardation, neurological abnormalities and dislocated ocular lenses. The biochemical basis for lack of enzyme activity in each case has been studied. All three have been shown to lack the sulphite oxidase protein, but in one case this appears to be secondary to a defect in synthesis of the molybdenum cofactor. Sulphite oxidase deficiency has been produced in the rat by administration of high levels of tungsten. Sulphite oxidase-deficient animals are particularly susceptible to the toxic effects of sulphite and atmospheric sulphur dioxide.
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PMID:The oxidation of sulphite in animals systems. 39 60

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 less than 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 51Cr, were more adherent to neutrophils, and permitted greater albumin transit than control monolayers. Treatment with tungsten, allopurinol, and/or superoxide dismutase decreased (P less than 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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PMID:Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity. 131 87

The hypothesis that posthypoxic renal injury is mediated by xanthine oxidase-derived oxygen free radical production was tested in an in vitro model of rat proximal tubule epithelial cells in primary culture subjected to 60 min of hypoxia and 30 min of reoxygenation. Hypoxia-reoxygenation-induced injury, measured as lactate dehydrogenase (LDH) release, was 54.0 +/- 7.1%. Inhibition of xanthine oxidase by 10(-4) M allopurinol attenuated injury (LDH release = 35.5 +/- 3.7%; P less than 0.01). Oxypurinol was similarly effective. Alternatively, cells were treated with 50 or 100 microM tungsten to inactivate xanthine oxidase. Tungsten prevented hypoxia-reoxygenation-induced superoxide radical production (basal = 97 +/- 8, hypoxia-reoxygenation = 172 +/- 12, and plus tungsten = 73 +/- 8 nmol/micrograms protein) and attenuated hypoxia-reoxygenation-induced injury (LDH release: basal = 18.8 +/- 3.0%, hypoxia-reoxygenation = 62.0 +/- 4.8%, plus 50 microM tungsten = 24.8 +/- 5.0%, and plus 100 microM tungsten = 6.0 +/- 0.7%). In addition, hypoxia and reoxygenation increased the ratio of xanthine oxidase to total activity (xanthine oxidase + xanthine dehydrogenase) from 73 to 100%. Therefore xanthine oxidase was responsible for hypoxia-reoxygenation-induced superoxide radical formation and hypoxia-reoxygenation-induced injury. Xanthine oxidase is likely to be the major source of oxygen free radicals during renal ischemia and reperfusion.
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PMID:Xanthine oxidase produces O2-. in posthypoxic injury of renal epithelial cells. 132 7

Injury to nonpulmonary organ systems often initiates systemic processes that cause recruitment of neutrophils to the lung. We found that rats subjected to intestinal ischemia-reperfusion (I/R) had increased transvascular leak of 125I-labeled albumin into lungs and decreased lung ATP levels (P less than 0.05). In addition, rats subjected to intestinal I/R had increased plasma xanthine oxidase (XO) activity, plasma leukotactic activity for neutrophils, and lung neutrophil retention (assessed by morphometry and myeloperoxidase activity) compared with sham-treated rats (P less than 0.05). By comparison, after intestinal I/R, rats fed an allopurinol- or tungsten-enriched diet had decreased plasma and intestinal XO activities, decreased plasma leukotacic and lung myeloperoxidase (MPO) activities, decreased lung leak, and increased lung ATP levels compared with rats fed control diets (P less than 0.05). Further studies suggested a more specific role for circulating rather than tissue XO in mediating lung neutrophil accumulation but not lung leak. Plasma XO, plasma leukotactic, and lung MPO activities, but not lung leak, increased in rats administered purified XO intravenously. In addition, plasma XO, plasma leukotactic, and lung MPO activities, but not lung leak, decreased in rats administered antisera against XO and then subjected to intestinal I/R. We conclude that circulating XO increases acutely and may contribute to pulmonary retention of neutrophils after an ischemic intestinal insult.
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PMID:Circulating xanthine oxidase mediates lung neutrophil sequestration after intestinal ischemia-reperfusion. 132 31

The conversion of xanthine dehydrogenase to xanthine oxidase and lipid peroxidation were measured in brain from carbon monoxide- (CO) poisoned rats. Sulfhydryl-irreversible xanthine oxidase increased from a control level of 15% to a peak of 36% over the 90 min after CO poisoning, while the conjugated diene level doubled. Reversible xanthine oxidase was 3-6% of the total enzyme activity over this span of time but increased to 31% between 90 and 120 min after poisoning. Overall, reversible and irreversible xanthine oxidase represented 66% of total enzyme activity at 120 min after poisoning. Rats depleted of this enzyme by a tungsten diet and those treated with allopurinol before CO poisoning to inhibit enzyme activity exhibited no lipid peroxidation. Treatment immediately after poisoning with superoxide dismutase or deferoxamine inhibited lipid peroxidation but had no effect on irreversible oxidase formation. Biochemical changes only occurred after removal from CO, and changes could be delayed for hours by continuous exposure to 1,000 ppm CO. These results are consistent with the view that CO-mediated brain injury is a type of postischemic reperfusion phenomenon and indicate that xanthine oxidase-derived reactive oxygen species are responsible for lipid peroxidation.
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PMID:Dehydrogenase conversion to oxidase and lipid peroxidation in brain after carbon monoxide poisoning. 144 8

Exposure to recombinant human tumor necrosis factor-alpha (TNF-alpha) or calcium ionophore (A23187) for 4 h increased (P less than 0.05) lactate dehydrogenase (LDH) release from cultured bovine brain endothelial cells (EC). In contrast, treatment with endotoxin or interleukin-1 did not increase (P greater than 0.05). LDH release from brain EC. Pretreatment with tungsten decreased (P less than 0.05) xanthine oxidase activity in brain EC and decreased (P less than 0.05) LDH release from brain EC following exposure to TNF. Our results suggest that TNF-alpha injures brain microvascular EC and that this effect may be mediated by xanthine oxidase.
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PMID:Tungsten treatment prevents tumor necrosis factor-induced injury of brain endothelial cells. 154 79

We have previously shown that gut ischemia/reperfusion (I/R) causes simultaneous liver and lung dysfunction and that neutrophils play a critical role in this process. The purpose of this study was to ascertain whether xanthine oxidase (XO) was likewise operational. Normal and XO-inactivated rats (given a tungsten-enriched, molybdenum-depleted diet for 3 weeks) underwent 45 minutes of occlusion of the superior mesenteric artery, and control rats were subjected to a sham laparotomy. After zero and six hours of reperfusion, blood was sampled and livers and lungs harvested. Iodine-125-labeled albumin leak was used as a marker for pulmonary and liver capillary permeability barrier function, and serum acetoacetate/3-hydroxybutyrate (AcAc/3-OHB) levels as an index of hepatic mitochondrial redox state. Gut ischemia/six hours of reperfusion (I/R) increased the 125I albumin lung/blood ratio and the 125I albumin liver/blood ratio; AcAc/3-OHB levels decreased significantly. Xanthine oxidase activation eliminated the observed lung and liver capillary leak as well as the hepatic metabolic derangement induced by gut I/R. In conclusion, the simultaneous lung and liver dysfunction produced by gut I/R is mediated by XO.
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PMID:Simultaneous liver and lung injury following gut ischemia is mediated by xanthine oxidase. 161 31

Bovine brain endothelial cells (EC) that were isolated and propagated in pure culture had increased (greater than 20-fold) levels of xanthine oxidase and xanthine dehydrogenase activity compared to whole brain homogenate. Brain EC also released superoxide anion (O2-) into the extracellular medium. Treatment of EC with tungsten decreased (P less than 0.05) both XO activity and O2- release. XO appears to be highly concentrated in cerebral vascular endothelium and may be an important source of O2-.
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PMID:Generation of superoxide anion by brain endothelial cell xanthine oxidase. 165 87

The role of xanthine oxidase in the mechanism of paraquat toxicity was assessed by in vitro and in vivo experiments. Paraquat stimulated the reduction of cytochrome c by xanthine-xanthine oxidase system in vitro. Paraquat, when added in vitro, stimulated hypoxanthine-dependent superoxide production in the cytosol of rat lung. Tungsten-feeding inhibits xanthine oxidase activity in a variety of tissues in experimental animals. Its therapeutic effect on paraquat intoxication was studied in this paper. In rats fed a tungsten-enriched diet for 5 weeks prior to intraperitoneal injection of 50 mg/kg paraquat dichloride, the mortality decreased significantly compared with rats fed a standard diet. Pretreatment with oxypurinol (1000 mg/kg, s.c.) also ameliorated the paraquat toxicity in rats. We conclude that xanthine oxidase plays an important role in paraquat toxicity and that xanthine oxidase inhibitors may become antidotes for paraquat intoxication.
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PMID:The role of xanthine oxidase in paraquat intoxication. 165 24

Our results suggest that xanthine oxidase (XO) contributes to lung neutrophil sequestration in hypovolemic shock. Catheterized rats subjected to shock by phlebotomy (approximately 30% blood loss) had decreased mean arterial blood pressures (P less than 0.05) and increased (P less than 0.05) lung myeloperoxidase (MPO) activities (indicative of lung neutrophil accumulation) compared with sham-treated normotensive rats. In contrast, rats depleted of lung and plasma XO activity by tungsten diet before phlebotomy had decreased (P less than 0.05) lung MPO activities compared with phlebotomized rats fed regular diets.
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PMID:Hypovolemic shock promotes neutrophil sequestration in lungs by a xanthine oxidase-related mechanism. 166 98


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