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)

14,15-3H-Norethisterone-4 beta, 5 beta-epoxide, a metabolite of norethisterone, was incubated with several proteins and nucleic acids. After 30 min incubation 0.19 nmol of the epoxide were irreversibly bound per mg albumin which contains free sulfhydryl groups; proteins without SH-groups, such as concanavalin A, gamma-globulin, DNA and RNA, did not irreversibly bind norethisterone epoxide. A superoxide (O2) generating enzyme system comprised of xanthine oxidase and hypoxanthine was capable of catalyzing the irreversible binding of the parent compound, norethisterone, to albumin, indicating that an oxidation product was formed which reacted with the protein. When norethisterone epoxide was incubated for 60 min with hepatic microsomes of rats in absence of NADPH, about 2.0 nmol of the epoxide were irreversibly incorporated per mg microsomal protein. This binding was increased to 5.2 nmol by addition of a NADPH regenerating system. Addition of glutathione and cytosol decreased only the NADPH-dependent protein binding; phenobarbital pretreatment of rats induced this NADPH-dependent binding of norethisterone epoxide to microsomal protein by a factor of 2. In presence of NADPH, binding of the epoxide to microsomal protein depended on substrate concentration used. The results indicate that norethisterone epoxide is able to chemically react with proteins. In addition, hepatic microsomal enzymes convert the epoxide to another metabolite which also can react with proteins.
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PMID:Irreversible protein binding of norethisterone (norethindrone) epoxide. 0 5

Methane (CH(4)) production from the anti-inflammatory agent, dimethyl sulfoxide (DMSO), was used to measure .OH from chemical reactions or human phagocytes. Reactions producing .OH (xanthine/xanthine oxidase or Fe(++)/EDTA/H(2)O(2)) generated CH(4) from DMSO, whereas reactions yielding primarily O-(2) or H(2)O(2) failed to produce CH(4). Neutrophils (PMN), monocytes, and alveolar macrophages also produced CH(4) from DMSO. Mass spectroscopy using d(6)-DMSO showed formation of d(3)-CH(4) indicating that CH(4) was derived from DMSO. Methane generation by normal but not chronic granulomatous disease or heat-killed phagocytes increased after stimulation with opsonized zymosan particles or the chemical, phorbol myristate acetate. Methane production from DMSO increased as the number of stimulated PMN was increased and the kinetics of CH(4) production approximated other metabolic activities of stimulated PMN. Methane production from stimulated phagocytes and DMSO was markedly decreased by purportedly potent .OH scavengers (thiourea or tryptophane) and diminished to lesser degrees by weaker .OH scavengers (mannitol, ethanol, or sodium benzoate). Superoxide dismutase or catalase also decreased CH(4) production but urea, albumin, inactivated superoxide dismutase, or boiled catalase had no appreciable effect. The results suggest that the production of CH(4) from DMSO may reflect release of .OH from both chemical systems and phagocytic cells. Interaction of the nontoxic, highly permeable DMSO with .OH may explain the anti-inflammatory actions of DMSO and provide a useful measurement of .OH in vitro and in vivo.
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PMID:Generation of hydroxyl radical by enzymes, chemicals, and human phagocytes in vitro. Detection with the anti-inflammatory agent, dimethyl sulfoxide. 50 Aug 30

Dietary AMP deficiency induces the morphogenesis of supernumerary gonopodes on abdominal segements. The AMP concentration threshold inducing supernumerary gonopodes depends on the lecithin and albumin concentration of the diet. The AMP concentration threshold corresponding to maximal xanthine oxidase activity depends to the maximal rate of protein biosynthesis. The results suggest the existence of a relation between the developmental physiology of Artemia and AMP and lipid metabolisms, relation which would imply the activity of xanthine oxidase.
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PMID:[Metabolic adaptation to a fatty diet: growth and morphogenesis of Artemia salina (L)]. 102 27

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

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

Hyperoxia has been suggested as a risk factor for kernicterus. The toxicity of hyperoxia may be mediated by free radicals. We investigated the effects of free radicals, formed by the hypoxanthine/xanthine oxidase system, with and without additional hyperoxia, on the accumulation of bilirubin and albumin in rat brain. Hypoxanthine was infused for 60 min into retrograde carotid catheters in awake, young, male SPRD rats. After 30 min the infusion was briefly interrupted to inject xanthine oxidase 1 U/kg through the same catheter. Group I (controls) received 0.9% NaCl in lieu of hypoxanthine/xanthine oxidase. Groups I and II breathed room air at all times, while group III breathed 90% O2. After 60 min all groups received a bolus dose of 125I-albumin through a peripheral venous catheter, followed by bilirubin 25 mg/kg for 5 min, then bilirubin 35 mg/kg for 55 min. There were no significant differences between the groups as regards serum bilirubin, serum albumin, brain bilirubin, or brain albumin. Neither during normoxic nor hyperoxic conditions did the hypoxanthine/xanthine oxidase system increase the accumulation of bilirubin or albumin in rat brain.
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PMID:The effects of hypoxanthine, xanthine oxidase and hyperoxia on the accumulation of bilirubin and albumin in young rat brain. 149 69

We examined the effects of tumor necrosis factor-alpha (TNF alpha) stimulation of endothelial cells on the increase in endothelial permeability induced by H2O2. Bovine pulmonary microvascular endothelial cells (BPMVEC) were grown to confluence on a microporous filter and the 125I-albumin clearance rate across the monolayer was determined. Pretreatment with TNF alpha (100 U/ml) for 6 h had no direct effect on transendothelial 125I-albumin permeability. However, TNF alpha pretreatment enhanced the susceptibility of BPMVEC to H2O2; that is, H2O2 (10 microM) alone had no direct effect, whereas H2O2 increased 125I-albumin permeability more than threefold when added to monolayers pretreated for 6 h with TNF alpha. Determination of lactate dehydrogenase release indicated that increased permeability was not due to cytolysis. We measured the intracellular contents of GSH and catalase to determine their possible role in mediating the increased susceptibility to H2O2. TNF alpha treatment (100 U/ml for 6 h) decreased total GSH content and concomitantly increased the oxidized GSH content, but did not alter the cellular catalase activity. The role of GSH was examined by pretreating endothelial cells with 2 mM GSH for 3 h, which produced an 80% increase in intracellular GSH content. GSH repletion inhibited the increased sensitivity of the TNF alpha-treated endothelial cells to H2O2. We tested the effects of xanthine oxidase (XO) inhibition since XO activation may be a source of oxidants responsible for the decrease in cellular GSH content. Pretreatment with 0.5 mM oxypurinol attenuated the synergistic effect of TNF alpha and H2O2 on endothelial permeability. The results indicate that decreased oxidant buffering capacity secondary to TNF alpha-induced reduction in intracellular GSH content mediates the increased susceptibility of endothelial cells to H2O2. This mechanism may contribute to oxidant-dependent vascular endothelial injury in septicemia associated with TNF alpha release.
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PMID:Tumor necrosis factor-alpha-mediated decrease in glutathione increases the sensitivity of pulmonary vascular endothelial cells to H2O2. 154 73

We investigated the effect of xanthine (X) plus xanthine oxidase (XO) on pulmonary microvascular endothelial permeability in isolated rabbit lungs perfused with Krebs buffer containing bovine serum albumin (5 g/100 ml). Addition of five mU/ml XO and 500 microM X to the perfusate caused a twofold increase in the pulmonary capillary filtration coefficient (Kf,c) 30 min later without increasing the pulmonary capillary pressure. This increase was prevented by allopurinol or catalase but not by superoxide dismutase or dimethyl sulfoxide. Because these data implicated hydrogen peroxide (H2O2) as the injurious agent, we measured its concentration in the perfusate after the addition of X and XO for a 60-min interval. In the absence of lung tissue and albumin, H2O2 increased with time, reaching a concentration of approximately 250 microM by 60 min. If albumin (5 g/100 ml) was added to the perfusate, or in the presence of lung tissue, the corresponding values were 100 microM and less than 10 microM, respectively. To understand the mechanisms of H2O2 scavenging by lung tissue, we added a 250 microM bolus of H2O2 to the lung perfusate. We found that H2O2 was removed rapidly, with a half-life of 0.31 +/- 0.04 (SE) min. This variable was not increased significantly by inhibition of lung catalase activity with sodium azide or inhibition of the lung glutathione redox cycle with 1-chloro-2,4-dinitrobenzene. However, inhibition of both enzymatic systems increased the half-life of H2O2 removal to 0.71 +/- 0.09 (SE) min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of extracellular reactive oxygen species injury to the pulmonary microvasculature. 160 78

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

We investigated the binding of highly purified soluble human C-reactive protein (CRP) to human neutrophils. Binding of CRP to neutrophils was rapid (50% of maximal binding occurred within 15 seconds), and complete within 5 minutes. Binding was inhibitable by excess unlabeled CRP, and nonspecific binding in the presence of a 200-fold excess of unlabeled CRP was 10% of total binding. Binding was not affected by other proteins, including albumin, fibronectin, rabbit IgG, or normal human plasma. Maximal binding required both calcium (0.5 mM) and magnesium (0.24 mM) ions. Calcium phosphorylcholine (10 micrograms/ml) or sodium citrate (10 micrograms/ml) completely dissociated bound CRP. Binding was saturable and most consistent with a 2-site model, demonstrating both a high-affinity receptor (1.4 x 10(4) sites/cell; Kd 3.7 x 10(-10) M) and a low-affinity receptor (4.2 x 10(5) sites/cell; Kd 2.5 x 10(-8) M). CRP at concentrations of 50 micrograms/ml inhibited the neutrophil superoxide production induced by phorbol ester. At concentrations of 100 micrograms/ml or greater, CRP also inhibited superoxide production in a cell-free xanthine oxidase-acetaldehyde system. These data suggest that CRP can down-regulate neutrophil oxidative capacity through interaction with receptors on neutrophils as well as by direct antioxidant activity.
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PMID:Binding of C-reactive protein to human neutrophils. Inhibition of respiratory burst activity. 165 Feb 22


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