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)

The effect of exposure of PMN to extracellular oxidants on the PMN oxidative burst on the subcellular location of CD64 (Fc gamma RI), CD32w (Fc gamma RII), CD16 (Fc gamma RIII), CD35 (complement receptor 1), and CD11b/CD18 (complement receptor 5) was studied. Incubation of PMN with glucose/glucose oxidase resulted in an intracellular shift in Fc gamma receptors from secretory vesicles to plasma membrane fractions while reducing complement receptor expression in plasma membrane fractions. Incubation of PMN with xanthine/xanthine oxidase resulted in an intracellular shift in Fc gamma receptors from specific granules to secretory vesicles. Incubation of PMN with xanthine/xanthine oxidase resulted in an intracellular shift from secretory vesicles to plasma membrane fractions for CD35 and from secretory vesicles and specific granules to plasma membrane fractions for CD11b/CD18. The effects of glucose/glucose oxidase and xanthine/xanthine oxidase on receptor redistribution were blocked by catalase and catalase and superoxide dismutase, respectively. Cytoskeleton stabilization with phalloidin and Taxol blocked the effect of glucose/glucose oxidase and xanthine/xanthine oxidase on Fc gamma and complement receptor relocation. Both H-7 and staurosporine abrogated the effect of glucose/glucose oxidase and xanthine/xanthine oxidase on Fc gamma receptor relocation, while genistein abrogated the effect of glucose/glucose oxidase and xanthine/xanthine oxidase on complement receptor relocation. Increases in CD64, CD32w, CD16, CD35, and CD11b/CD18 expression associated with plasma membrane fractions corresponded to functional increases in monomeric IgG binding, E-IV.3, (sheep erythrocyte opsonized with monoclonal antibody IV.3 directed against CD32w) E-Con A, EC3b, and EC3bi rosetting. These studies indicate that exposure of PMN to extracellular oxidants does not occur as an isolated event but results in a coordinated subcellular relocation of opsonic receptors which corresponds to changes in PMN function.
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PMID:Subcellular location of neutrophil opsonic receptors is altered by exogenous reactive oxygen species. 758 83

Our previous studies have shown that isolated adult rat cardiomyocytes with normal and reduced Cu/Zn SOD activities are equally susceptible to extracellularly generated oxidants (hydrogen peroxide, glucose oxidase/glucose and xanthine oxidase/xanthine systems). In the present study we exposed myocytes with reduced SOD activity to doxorubicin (adriamycin). Cardiotoxicity of doxorubicin has been attributed to the production of superoxide anion inside the cell. Cardiomyocytes with reduced SOD activity, but normal ATP content and viability, were obtained by the treatment of isolated cells with diethyldithiocarbamate (DDC). DDC-treated myocytes were significantly less resistant to doxorubicin than controls. Doxorubicin-stimulated superoxide anion formation, measured by the rate of SOD-inhibitable acetylated cytochrome C reduction, was significantly higher in the cytosolic fraction of DDC-treated cells compared to controls. These results indicate that for isolated cardiac myocytes an essential part of cytotoxicity of doxorubicin can be explained by the formation of superoxide anion and that the level of intracellular SOD activity should be considered as a significant factor for cell protection.
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PMID:Effects of doxorubicin on cardiomyocytes with reduced level of superoxide dismutase. 764 16

The aim of the research was to study the role played by extracellular O2-radicals, which are implicated in cardiac cell damage and the protective effect by cell-permeable, nitroxide, superoxide dismutase-mimics. Cardiomyocytes cultures from 1-day-old rats served as the test-system. Experiments were performed since 5th day in culture when > 80% of the cells were beating myocardial cells. Oxidative damage was induced by 0.5 mM hypoxanthine and 0.06 U/ml xanthine oxidase or by 10 mM glucose and 0.15 U/ml glucose oxidase. The parameters used to evaluate damages were spontaneous beating, lactate dehydrogenase release and ATP level. The rhythmic pulsation was followed microscopically. To determine the kinetics of cytosolic enzyme release from the cells, media samples were collected at various points of time and assayed for enzyme activity. To determine the cellular ATP, cells were washed with sodium phosphate buffer, scraped off and boiled for 3 min with sodium phosphate buffer. Following centrifugation the supernatant was collected and ATP was determined by the chemiluminogenic assay using firefly tails. The present results indicate that nitroxide stable free radicals in the millimolar concentration range, provide full protection without toxic side-effect. Unlike exogenously added SOD that failed to protect, exogenous catalase provided almost full protection. In addition, the metal-chelating agent dipyridyl, but not diethylene-triamine-pentaacetate or desferrioxamine, protected the cultured cells. The present results suggest that H2O2 is the predominant toxic species mediating the oxidative damage whereas extracellular superoxide radical does not contribute to cultured cardiomyocyte damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Do nitroxides protect cardiomyocytes from hydrogen peroxide or superoxide? 767 30

The oxidized intermediates generated upon exposure of bovine liver catalase to hydrogen peroxide (H2O2) and superoxide radical (O2-) fluxes were examined with UV-visible spectrophotometry. H2O2 and O2- were generated by means of glucose/glucose oxidase and xanthine/xanthine oxidase systems. Serial overlay of absorption spectra in the Soret (350-450 nm) and visible (450-700 nm) regions showed that three oxidized intermediates, namely Compounds I, II and III, can be observed upon exposure of catalase to enzymatically generated H2O2 and O2-. Compound I is formed during the reaction of native enzyme with H2O2 and disappears in two ways: (i) via the catalytic reaction with H2O2 to restore native catalase and (ii) via the reaction with O2- to form Compound II. At low H2O2 concentrations (< 4.8 x 10(-9) M H2O2), Compound II reverts towards the native state mainly in a direct one-step reaction, whereas at higher H2O2 concentrations the pathway of Compound II back to the native enzyme involves Compound III. Formation of the latter from Compound II and H2O2 is irreversible and the rate constant of this reaction is 6.1 +/- 0.2 x 10(4) M-1 s-1. The formation of Compound III through the direct reaction of O2- with native enzyme has also been observed. Depending on the experimental conditions, the inactivation of catalase by O2- can be due to accumulation of Compound II ("slow" inhibition) or to the formation of Compound III ("rapid" inhibition) part of which leads to a dead end product. Formation of Compound III and of this dead end product are responsible for the irreversible inactivation in presence of an excess of H2O2.
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PMID:Reactions of bovine liver catalase with superoxide radicals and hydrogen peroxide. 775 1

Previous studies have shown that susceptibilities of hepatocytes and endothelial cells to H2O(2)-induced injury are altered by changes in the intracellular activity of Cu,Zn-containing superoxide dismutase (CuZn-SOD). To evaluate the role of intracellular CuZn-SOD in oxidant-induced injury to rat cardiac myocytes, cells with reduced CuZn-SOD activity but normal ATP content were either isolated from the hearts of adult copper-deficient rats or obtained by treatment of normal isolated adult myocytes with diethyldithiocarbamate. These myocytes and controls with normal CuZn-SOD activity were exposed to either reagent H2O2 or oxidants generated by extracellular glucose oxidase plus glucose or xanthine oxidase plus xanthine. It was shown that myocytes with CuZn-SOD activities reduced by 70-90% were equally susceptible to H2O2 and the two oxidant-generating systems as the control myocytes. The findings suggest that in adult cardiac myocytes, in contrast to the situation in some other cells, intracellular CuZn-SOD may not have a significant defensive role against acute H2O(2)-induced injury. The possibility remains, however, that changes in the activity of this enzyme, e.g., in copper deficiency, may be relevant to the ability of myocytes to cope with chronic oxidative stress resulting from imbalance between intracellular oxygen radical-generating and -scavenging systems.
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PMID:Role of intracellular SOD in oxidant-induced injury to normal and copper-deficient cardiac myocytes. 790 Aug 65

The effect of xanthine oxidase (XO)-mediated oxidant stress on endothelial cell signal transduction was determined in bradykinin-stimulated cells loaded with the Ca+(+)-sensitive probe fura-2. Calf pulmonary artery endothelial cells were incubated with a reaction mixture containing XO (50 mU/ml) and its substrate, hypoxanthine (HX) (0.5 mM), for periods of 0.5 to 2.0 hr. HX/XO time dependently increased basal cytosolic free Ca++ ([Ca++]i) and decreased the response of [Ca++]i to bradykinin, so that incubation of cells with HX/XO for 1.5 hr or longer eliminated responsiveness to agonist. In presence of XO, HX dose dependently increased basal [Ca++]i (EC50 approximately 3 x 10(-5) M) and decreased the response of [Ca++]i to bradykinin. Sequential application of bradykinin and Ca++ to cells suspended in Ca+(+)-free/EGTA buffer was performed to characterize the effects of HX/XO on receptor-activated Ca++ entry and release of Ca++ from internal stores. HX/XO attenuated internal store Ca++ release and inhibited the bradykinin-stimulated Ca++ influx pathway in a time-dependent manner. When the HX dose was decreased by an order of magnitude, HX/XO selectively inhibited the agonist-stimulated influx pathway with little effect on internal store Ca++ release. Coincubation with superoxide dismutase tended to potentiate the effects of HX/XO, whereas catalase provided almost complete protection. Similar results to HX/XO-induced alterations in Ca++ signaling were observed when glucose-glucose oxidase (G/GO) was used as the oxidant-generating system. Inhibition of Ca++ signaling by HX/XO and G/GO occurred in the absence of decreased cell viability. Together, these results suggest that HX/XO-induced inhibition of signal transduction in endothelial cells is a function of H2O2-mediated oxidant stress and represents an early dysfunction in the process of oxidant injury.
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PMID:Xanthine oxidase inhibits transmembrane signal transduction in vascular endothelial cells. 793 72

The present study was carried out to examine the role of reactive oxygen species in mediating the melanogenic effects of UVR. B16 mouse melanoma cells responded to a single dose of UVR by showing increases in their melanin content. Although there was a small increase in melanin at 48-72 hours, which was associated with a rise in tyrosinase activity at 48 h, the greatest change occurred at 3 h and this was not associated with an increase in tyrosinase activity. This short-term response, unlike the more delayed melanogenic response, was reduced by superoxide dismutase (SOD). Xanthine oxidase (XO), which generates the superoxide anion (O2-), also increased the melanin content of B16 melanoma cells with effects at 3 h and 48 h. As with UVR, the delayed response was accompanied by an increase in tyrosinase activity but no such association was evident at 3 h. In addition, the short-term effect, like that seen with UVR, was reduced with SOD and to a lesser extent with catalase. In contrast to the effects found with XO, glucose oxidase, which generates hydrogen peroxide, had no effect on the melanin content or tyrosinase activity of the B16 cells. These results confirm previous observations that UVR is able to act directly on cells to bring about delayed increases in melanogenesis. They further demonstrate that UVR also stimulates melanogenesis through a more rapid action that is not associated with an activation of tyrosinase. This effect could be mediated by the O2- which, rather than activating tyrosinase, could act by serving as a substrate for the enzyme.
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PMID:The superoxide anion may mediate short- but not long-term effects of ultraviolet radiation on melanogenesis. 795 23

Exposure of human nasal ciliated epithelium to reactive oxidants generated by the enzymatic xanthine-xanthine oxidase superoxide/hydrogen peroxide (H2O2) and glucose-glucose oxidase H2O2-generating systems, or to reagent H2O2 or hypochlorous acid (HOCl) resulted in significant alterations in ciliary beating. The earliest change noted was the presence of ciliary slowing, progressing eventually to complete ciliary stasis in some areas. Ciliary dyskinesia was seen within the first hour, often from as early as 15 min after exposure of the cells to reactive oxidants. Using peroxidases, various antioxidant enzymes, and oxidant scavengers, we confirmed that these detrimental effects on ciliary function were mediated primarily by H2O2 and HOCl. Moreover, 3-aminobenzamide (3-ABA), an inhibitor of the DNA repair enzyme poly ADP ribose polymerase, prevented H2O2-mediated inhibition of ciliary function, indicating that oxidant-mediated damage to DNA may well be the basis of the effects of H2O2 on ciliated epithelium. Acute and chronic inflammatory responses may therefore present the possible threat of H2O2- or HOCl-inflicted injury on bystander respiratory epithelium, leading to ciliary dyskinesia and slowing.
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PMID:Oxidant-mediated ciliary dysfunction in human respiratory epithelium. 795 61

The oxidized intermediates generated upon exposure of Aspergillus niger catalase to hydrogen peroxide and superoxide radical fluxes were examined with UV-visible spectrophotometry. Hydrogen peroxide and superoxide radical were generated by means of glucose/glucose oxidase and xanthine/xanthine oxidase systems. Serial overlay of absorption spectra in the Soret (350-450 nm) and visible regions (450-700 nm) showed that the decomposition of hydrogen peroxide by the catalase of Aspergillus niger can proceed through one of two distinct pathways: (i), the normal "catalatic" cycle consisting of ferric catalase-->Compound I-->ferric catalase; (ii), a longer cycle where superoxide radical transforms Compound I to Compound II which is then converted to the resting ferric enzyme via Compound III. The latter sequence of reactions ensures that the catalase of Aspergillus niger restores entirely its activity upon exposure to low levels of superoxide radicals due to the actions of oxidases.
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PMID:Characterization of hydrogen peroxide and superoxide degrading pathways of Aspergillus niger catalase: a steady-state analysis. 801 20

We aimed to determine the status of iron in mediating oxidant-induced damage to cultured bovine aortic endothelial cells. Chromium-51-labeled cells were exposed to reaction mixtures of xanthine oxidase/hypoxanthine and glucose oxidase/glucose; these produce superoxide and hydrogen peroxide, or hydrogen peroxide, respectively. Xanthine oxidase caused a dose dependent increase of 51Cr release. Damage was prevented by allopurinol, oxypurinol, and extracellular catalase, but not by superoxide dismutase. Prevention of xanthine oxidase-induced damage by catalase was blocked by an inhibitor of catalase, aminotriazole. Glucose oxidase also caused a dose-dependent increase of 51Ci release. Glucose oxidase-induced injury, which was catalase-inhibitable, was not prevented by extracellular superoxide dismutase. Both addition of and pretreatment with deferoxamine (a chelator of Fe3+) prevented glucose oxidase-induced injury. The presence of phenanthroline (a chelator of divalent Fe2+) prevented glucose oxidase-induced 51Cr release, whereas pretreatment with the agent did not. Apotransferrin (a membrane impermeable iron binding protein) failed to influence damage. Neither deferoxamine nor phenanthroline influenced cellular antioxidant defenses, or inhibited lysis by non-oxidant toxic agents. Treatment with allopurinol and oxypurinol, which inhibited cellular xanthine oxidase, failed to prevent glucose oxidase injury. We conclude that (1) among the oxygen species extracellularly generated by xanthine oxidase/hypoxanthine, hydrogen peroxide induces damage via a reaction on cellular iron; (2) deferoxamine and phenanthroline protect cells by chelating Fe3+ and Fe2+, respectively; and (3) reduction of cellular stored iron (Fe3+) to Fe2+ may be prerequisite for mediation of oxidant-induced injury, but this occurs independently of extracellular superoxide or cellular xanthine oxidase-derived superoxide.
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PMID:Reactive oxygen metabolite-induced toxicity to cultured bovine endothelial cells: status of cellular iron in mediating injury. 802 Dec 93


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