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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xanthine oxidase (XO) and xanthine dehydrogenase (XD) activities decreased in lungs isolated from rats and cultured lung endothelial cells that had been exposed to hyperoxia. Purified XO activity also decreased after addition of a variety of chemically generated O2 metabolite species (superoxide anion, hydrogen peroxide, hydroxyl radical, or hypochlorous acid), hypoxanthine, or stimulated neutrophils in vitro. XO inactivation by chemically, self-, or neutrophil-generated O2 metabolites was decreased by simultaneous addition of various O2 metabolite scavengers but not their inactive analogues. Since XO appears to contribute to a variety of biological processes and diseases, hyperoxia- or O2 metabolite-mediated decreases in XO activity may be an important cellular control mechanism.
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PMID:Hyperoxia and self- or neutrophil-generated O2 metabolites inactivate xanthine oxidase. 320 79

Preexposure to hypoxia increased survival and lung reduced glutathione-to-oxidized glutathione ratios (GSH/GSSG) and decreased pleural effusions in rats subsequently exposed to continuous hyperoxia. In addition, lungs from hypoxia-preexposed rats developed less acute edematous injury (decreased lung weight gains and lung lavage albumin concentrations) than lungs from normoxia-preexposed rats when isolated and perfused with hydrogen peroxide (H2O2) generated by xanthine oxidase (XO) or glucose oxidase (GO). In contrast, when perfused with elastase or exposed to a hydrostatic left atrial pressure challenge, lungs isolated from hypoxia-preexposed rats developed the same acute edematous injury as lungs from normoxia-preexposed rats. The mechanism by which hypoxia preexposure conferred protection against H2O2 appeared to depend on hexose monophosphate shunt (HMPS)-dependent increases in lung glutathione redox cycle activity. First, before perfusion with GO, lungs from hypoxia-preexposed rats had increased glutathione peroxidase and glucose 6-phosphate dehydrogenase (but not catalase or glutathione reductase) activities compared with lungs from normoxia-preexposed rats. Second, after perfusion with GO, lungs from hypoxia-preexposed rats had increased H2O2 reducing equivalents, as reflected by increased GSH/GSSG and NADPH/NADPH+, compared with lungs from normoxia-preexposed rats. Third, pretreatment of rats with an HMPS inhibitor, (6-aminonicotinamide) or a glutathione reductase inhibitor, [1,3-bis(2-chloroethyl)-1-nitrosourea] prevented hypoxia-conferred protection against H2O2-mediated acute edematous injury in isolated lungs. These findings suggest that increased detoxification of H2O2 by glutathione redox cycle and HMPS-dependent mechanisms contributes to tolerance to hyperoxia and resistance to H2O2 of lungs from hypoxia-preexposed rats.
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PMID:Hypoxia increases glutathione redox cycle and protects rat lungs against oxidants. 321 62

The potential protective effect of N-acetylcysteine against various types of oxidative stress (exposure to hyperoxia, treatment with paraquat, incubation in the presence of the hypoxanthine-xanthine oxidase system) was tested in primary cultures of porcine aortic endothelial cells. It was compared to that of selenomethionine (Se-Met), known to increase glutathione peroxidase activity, when given either alone or in combination with N-acetylcysteine. LDH release, 3H-thymidine (TdR) incorporation into DNA and DNA content were measured to assess the cytotoxic effect of the conditions tested. Total and oxidized glutathione content was also determined. Whereas Se-Met had a partial protective effect on all the conditions but paraquat treatment, N-acetylcysteine administration had no effect on the hyperoxia induced changes and significantly worsened the cytotoxic action of paraquat. On the other hand, LDH release following an incubation in the presence of the hypoxanthine-xanthine oxidase was significantly reduced after N-acetylcysteine treatment. No major change in total nor in oxidized glutathione followed N-acetylcysteine treatment in control and experimental conditions. A dose-dependent protective effect of N-acetylcysteine was obtained when this agent was given concomitantly with the xanthine oxidase system. These data suggest that in cultured endothelial cells a N-acetylcysteine-related protective effect, if present, is most likely to result from the direct scavenging action of N-acetylcysteine.
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PMID:Comparative study on the selenium- and N-acetylcysteine-related effects on the toxic action of hyperoxia, paraquat and the enzyme reaction hypoxanthine-xanthine oxidase in cultured endothelial cells. 368 96

Both distal (canine lung strips) and proximal (bovine trachealis strips) airway smooth muscle contract in isolated organ baths as the percentage of environmental oxygen is increased from 12% to 95%. This effect is blocked by prostaglandin synthetase inhibitors (indomethacin, 10(-4)M; meclofenamate, 10(-4)M). To determine whether this contractile response is due to molecular oxygen, or to other products of oxidative metabolism, we examined the effects of ozone, hydrogen peroxide, and superoxide radical generating systems (paraquat and xanthine-xanthine oxidase) on the smooth muscle preparations. Ozone (3 ppm), paraquat (2 mM), and xanthine (10(-3)M)-xanthine oxidase (1 unit) were without effect. Hydrogen peroxide (10(-5)-10(-3)M) produce consistent contractions in both preparations, an effect which was appreciably greater in an hypoxic environment and which was blocked by both indomethacin and meclofenamate. Contraction from both hyperoxia and hydrogen peroxide was partially reversed by various oxygen radical scavengers, including methional (10 mM), ascorbic acid (10 mM), nitroblue tetrazolium (0.3 mM), butylated hydroxyanisole (1 mM), and 2',7' naphthalonediol (1 mM). These results suggest that hyperoxic contraction in airway smooth muscle is mediated by active oxygen species, perhaps by their effects on prostaglandin metabolism.
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PMID:Hydrogen peroxide contracts airway smooth muscle: a possible endogenous mechanism. 733 Apr 88

Endothelial cells are critical targets in both hypoxia- and reoxygenation-mediated lung injury. Reactive O2 species (ROS) have been implicated in the pathogenesis of hypoxic and reoxygenation lung injury, and xanthine dehydrogenase/oxidase (XDH/XO) is a major generator of the ROS. Porcine pulmonary artery endothelial cells (PAEC) have no detectable XDH/XO. This study was undertaken to examine 1) ROS production by hypoxic porcine PAEC and their mitochondria and 2) ROS production and injury in reoxygenated PAEC lacking XDH/XO activity. Intracellular H2O2 generation and extracellular H2O2 and O2 divided release were measured after exposure to normoxia (room air-5% CO2), hypoxia (0% O2-95% N-5% CO2), or hypoxia followed by normoxia or hyperoxia (95% O2-5% CO2). Exposure to hypoxia results in significant reductions in intracellular H2O2 formation and extracellular release of H2O2 and O2 by PAEC and mitochondria. The reductions occur with as little as a 2 h exposure and progress with continued exposure. During reoxygenation, cytotoxicity was not observed, and the production of ROS by PAEC and their mitochondria never exceeded levels observed in normoxic cells. The absence of XDH/XO may prevent porcine PAEC from developing injury and increased ROS production during reoxygenation.
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PMID:Effect of hypoxia and reoxygenation on the formation and release of reactive oxygen species by porcine pulmonary artery endothelial cells. 762 87

Aconitase is a member of a family of iron-sulfur-containing (de)hydratases whose activities are modulated in bacteria by superoxide radical (O2-.)-mediated inactivation and iron-dependent reactivation. The inactivation-reactivation of aconitase(s) in cultured mammalian cells was explored since these reactions may impact important and diverse aconitase functions in the cytoplasm and mitochondria. Conditions which increase O2-. production including exposure to the redox-cycling agent phenazine methosulfate (PMS), inhibitors of mitochondrial ubiquinol-cytochrome c oxidoreductase, or hyperoxia inactivated aconitase in mammalian cells. Overproduction of mitochondrial Mn-superoxide dismutase protected aconitase from inactivation by PMS or inhibitors of ubiquinol-cytochrome c oxidoreductase, but not from normobaric hyperoxia. Aconitase activity was reactivated (t1/2 of 12 +/- 3 min) upon removal of PMS. The iron chelator deferoxamine impaired reactivation and increased net inactivation of aconitase by O2-.. The ability of ubiquinol-cytochrome c oxidoreductase-generated O2-. to inactivate aconitase in several cell types correlated with the fraction of the aconitase activity localized in mitochondria. Extracellular O2-. generated with xanthine oxidase did not affect aconitase activity nor did exogenous superoxide dismutase decrease aconitase inactivation by PMS. The results demonstrate a dynamic and cyclical O2-.-mediated inactivation and iron-dependent reactivation of the mammalian [4Fe-4S] aconitases under normal and stress conditions and provide further evidence for the membrane compartmentalization of O2-..
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PMID:Superoxide radical and iron modulate aconitase activity in mammalian cells. 776 42

Recent studies have demonstrated that xanthine dehydrogenase/xanthine oxidase (XD/XO) activities of bovine endothelial cells (EC) are inversely regulated by O2 tensions to which the cells are exposed. We have confirmed these reports and extended the observation to a variety of cells from other sources. All EC that had detectable XD/XO activity demonstrated the greatest activity at the lowest O2 level. Bovine pulmonary artery smooth muscle cells showed XD/XO activity only under hypoxic conditions. The ratio of XO to XO+XD did not change significantly under various O2 concentrations for all cell types tested. Treatment of bovine pulmonary artery and rat epididymal fat pad EC with actinomycin D (1 microgram/ml), an inhibitor of transcription, suppressed XO and XO+XD activities in cells exposed both to 20 and 3% O2. High-dose cycloheximide (5 micrograms/ml), an inhibitor of translation, also reduced XO and XO+XD activities in these cells, whereas low-dose cycloheximide (0.5 microgram/ml) enhanced the stimulatory effect of hypoxia on XO+XD activity. We developed a digoxigenin-labeled probe that recognizes and hybridizes to rat XD cDNA and used it to examine the effect of O2 concentration on XD/XO mRNA expression of rat epididymal fat pad EC. XD/XO mRNA concentration was increased in cells exposed to hypoxia and decreased in cells exposed to hyperoxia compared with normoxic cells. The increase in mRNA concentration resulting from exposure to hypoxia was enhanced by cycloheximide. There was no change in XD/XO mRNA stability in cells exposed to hypoxia compared with normoxia. We conclude that the regulation of XD/XO by oxygen tension most likely occurs at the transcriptional level.
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PMID:Regulation of endothelial cell xanthine dehydrogenase xanthine oxidase gene expression by oxygen tension. 814 12

Neutrophil accumulation in alveolar spaces is a conspicuous finding in hyperoxia-exposed lungs. We hypothesized that xanthine oxidase (XO)-derived oxidants contribute to retention of neutrophils in hyperoxic lungs. Rats were subjected to normobaric hyperoxia (100% O2) for 48 h, and lungs were assessed for neutrophil sequestration (morphometry and lavage cell counts) and injury (lavage albumin levels and lung weights). In rats exposed to hyperoxia, we found increased (P < 0.05) lung neutrophil retention, lavage albumin levels, and lung weights compared with normoxia-exposed control rats. Suppression of XO activity by pretreatment with allopurinol decreased (P < 0.05) lung neutrophil retention but increased (P < 0.05) lavage albumin concentrations and lung weights in hyperoxic rats. Allopurinol treatment had no effect (P > 0.05) on the numbers of macrophages or lymphocytes recoverable by lung lavage. Depletion of XO activity by an independent method, tungsten feeding, also decreased (P < 0.05) lung lavage neutrophil counts and increased (P < 0.05) lavage albumin concentrations. We conclude that XO may be involved in lung neutrophil retention but not lung injury during exposure to hyperoxia.
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PMID:Xanthine oxidase promotes neutrophil sequestration but not injury in hyperoxic lungs. 817 9

Exposure to hyperbaric oxygen [3 atmospheres absolute (ATA) for 45 min] inhibited carbon monoxide (CO)-mediated lipid peroxidation in the brains of rats by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion process known to be due to the action of leukocytes. The effect was the same whether treatment was given 24 hr before or up to 45 min after poisoning. Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, based on measurements of myeloperoxidase (MPO) in microvessel segments, but persistent adherence, which is due to B2 integrins, did not occur. Exposing rats to 3 ATA pressure (0.21 ATA O2) after CO poisoning had no significant effects. A progressive reduction in brain microvessel MPO titers occurred with exposure to O2 at 1, 2, or 3 ATA after CO poisoning, but 1 ATA O2 treatment did not significantly inhibit xanthine oxidase formation or lipid peroxidation. In vitro studies with polymorphonuclear leukocytes (PMN) from rats exposed to hyperbaric oxygen corroborated the absence of PMN B2 integrin function, but when these cells were stimulated they exhibited normal B2 integrin expression on their surface and also normal elastase release and superoxide radical production. Adherence functions of PMN that do not require B2 integrins appeared to remain intact after exposure to hyperbaric oxygen, as peritoneal neutrophilia in response to a glycogen challenge was not inhibited. B2 integrin function could be restored by incubating cells with 8 bromo cGMP, and incubation with phorbol ester stimulated the adherence function of both control and hyperbaric oxygen-exposed PMN. These results provide a clear mechanism for the inhibition of CO-mediated brain lipid peroxidation by hyperbaric oxygen and indicate that hyperoxia causes a discrete disturbance of PMN adherence function.
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PMID:Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. 824 32

This multifaceted study involved a combined biochemical and cellular analysis of oxidant metabolism by a lung cell at risk from injury by endogenous and environmental oxidants, the pulmonary alveolar type II epithelial cell. Within the framework of this study, a method was developed for effectively delivering antioxidant enzymes and alpha-tocopherol to the intracellular compartment of alveolar epithelial cells. Alveolar type II cells are key sources of pulmonary surfactant phospholipids and apoproteins and serve as progenitors of type I alveolar epithelium, thus playing an important role in the re-epithelialization of the lung alveolus after exposure to pulmonary oxidants. The type I and II pulmonary epithelium also play an essential collaborative role in maintaining the integrity of the air-blood barrier of the lung. Because of these critical properties of the alveolar epithelium and their recognized sensitivity to oxidant stress derived from diverse sources, such as activated inflammatory cells, hyperoxia, the environmental oxidants and nitrogen dioxide, and surgical procedures, such as cardiopulmonary bypass and lung transplantation, we endeavored to understand more about the oxidant metabolism and antioxidant pharmacology of these cells. In our experiments, we made the observation that loss of differentiated oxidant generation and antioxidant properties of type II cells occurs very rapidly in vitro. For example, we observed a 50% to 75% reduction in the specific activities of type II cell superoxide dismutase, catalase, and glutathione peroxidase, all critical scavengers of cell superoxide and hydrogen peroxide and key enzymes in the attenuation of hydroxyl radical formation. Although the differentiated characteristics of the type II cell antioxidant defenses changed in vitro, they may have become more reflective of type I alveolar epithelial cells. The type I cell is the most vulnerable for oxidant damage in the alveolus because of its large surface area and the possibility of a reduced antioxidant capacity compared to type II alveolar epithelium. In spite of this limitation, we were able to culture type II cells and study their adaptive and toxic responses to exogenously administered oxidant stress. We also observed that a significant source of self-generated oxidants in type II cells was the enzyme xanthine oxidase. Normal rates of oxidant production by this enzyme had an inhibitory effect on incorporation of biosynthetic precursors into surfactant phospholipids; these effects were eliminated by the xanthine oxidase inhibitor, allopurinol.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Oxidant injury to the alveolar epithelium: biochemical and pharmacologic studies. 843 7


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