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 effects of cellular mediators that contribute to ischemia-induced neuronal degeneration on gamma-aminobutyric acid (GABAA)-receptor function were studied. In vitro, phospholipase A2 (PLA2) inhibited muscimol-induced 36Cl- uptake in cerebral cortical synaptoneurosomes. The major hydrolysis product of PLA2 activity, arachidonic acid, also inhibited GABA-mediated 36Cl- uptake. The unsaturated nature of arachidonic acid makes it (and its metabolites) highly susceptible to peroxidation by oxygen radicals. Incubation of synaptoneurosomes with the superoxide radical-generating system, xanthine and xanthine oxidase, decreased muscimol-induced 36Cl- uptake, suggesting that the peroxidation of arachidonic acid and/or its metabolites interferes with GABAA-receptor function. Another factor involved in ischemia-induced neuronal degeneration is an increase in intracellular Ca2+. Calcium also inhibited GABA-mediated 36Cl- flux, consistent with its ability to activate PLA2. In contrast, Mg2+, which blocks Ca2+ channels, enhanced muscimol-induced 36Cl- uptake, consistent with its neuroprotective effects. Each of these cellular processes is activated during cerebral ischemia and can lead to neuronal degeneration. We used a model of transient forebrain ischemia in gerbils to determine if GABAA-receptor regulation is altered in vivo at a time when CA1 hippocampal cells have degenerated. Four days after a 5 minute bilateral carotid artery occlusion, receptor autoradiography was performed to measure the binding of [35S]t-butylbicyclophosphorothionate (TBPS) to the GABA-gated chloride channel. Significant decreases in TBPS binding were observed only in the dendritic layers (stratum oriens and lacunosem moleculare) of the CA1 hippocampus. The results suggest that ischemia-induced cellular processes that contribute to cell death can decrease GABA-gated chloride channels on dendrites of CA1 pyramidal cells, and that GABAA receptors may also reside on neurons afferent to or intrinsic to the dendritic layers of CA1 hippocampus.
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PMID:Cellular regulation of the benzodiazepine/GABA receptor: arachidonic acid, calcium, and cerebral ischemia. 131 67

The effects of omeprazole on polymorphonuclear neutrophil (PMN) chemotaxis, superoxide generation, degranulation and translocation of cytochrome b-245 were investigated. Omeprazole (10(-6) - 5 x 10(-3) mol/l) reduced chemotaxis under agarose in a dose dependent manner, and the effect was irreversible. Superoxide anion generation was inhibited 50% at a concentration of 2.5 x 10(-5) mol/l and completely abolished at 5 x 10(-3) mol/l. Acid degraded omeprazole also inhibited O2- generation. Omeprazole did not scavenge O2- generated in a cell free xanthin-xanthine oxidase system. Degranulation by PMNs was inhibited only by omeprazole in concentrations above 10(-4) mol/l. Translocation of cytochrome b-245, essential for generation of O2-, was not affected by omeprazole. In conclusion, the anti-ulcer agent omeprazole in concentrations obtained during intravenous administration may inhibit the function of PMNs in vitro.
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PMID:Effects of omeprazole on neutrophil chemotaxis, super oxide production, degranulation, and translocation of cytochrome b-245. 131 81

The inhibition of xanthine oxidase by its reaction product, uric acid, was studied by steady state kinetic analysis. Uric acid behaved as an uncompetitive inhibitor of xanthine oxidase with respect to the reducing substrate, xanthine. Under 50 microM xanthine and 210 microM oxygen, the apparent K(i) for uric acid was 70 microM. Uric acid-mediated xanthine oxidase inhibition also caused an increase in the percentage of univalent reoxidation of the enzyme (superoxide radical production). Steady-state rate equations derived by the King-Altman method support the formation of an abortive-inhibitory enzyme-uric acid complex (dead-end product inhibition). Alternatively, inhibition could also depend on the reversibility of the classical ping-pong mechanism present in xanthine oxidase-catalyzed reactions.
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PMID:Inhibition of xanthine oxidase by uric acid and its influence on superoxide radical production. 132 3

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

We have studied the pathogenesis of murine cytomegalovirus (MCMV) pneumonitis in immunocompetent ICR mice and in mice treated with cyclophosphamide (CP). Intranasal infection of immunocompetent mice with MCMV resulted in transient and self-limited pulmonary lesions. When mice were given 200 mg/kg of CP one day before virus infection, transient splenic atrophy and subsequent splenic hypertrophy were induced, and the lesions in the lung were markedly augmented in their number and size although there was no significant enhancement of the virus growth. The augmentation coincided with the period of splenic hypertrophy. A marked increase in the number of pulmonary lesions was also induced in mice given 100 mg/kg of CP every 4 days following the initial dose of 200 mg/kg. In these mice, however, continuous splenic atrophy and augmented replication of MCMV in the lung were observed. When the activity of xanthine oxidase (XO) in lung tissue homogenates was measured, the activity was found to significantly increase after intranasal infection with MCMV irrespective of CP administration and there was a good correlation between the elevation of XO activity and the degree of pathological changes in the lung. In addition, we found that the administration of allopurinol, a specific inhibitor of XO and superoxide dismutase, a superoxide radical scavenger, reduced the number of the pulmonary lesions. These results suggest that superoxide radicals are involved in the pathogenesis of MCMV-associated pneumonitis in ICR mice.
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PMID:Pathogenesis of cytomegalovirus-associated pneumonitis in ICR mice: possible involvement of superoxide radicals. 133 50

The ability of the superoxide radical (SOR) generated by xanthine oxidase to activate phospholipase A2 (PLA2) was examined in microsomes prepared from luteinized rat ovaries. Treatment of microsomes with xanthine oxidase resulted in a rapid burst in SOR formation followed by an increase in PLA2 activity. Stimulation of PLA2 activity was dose related and similar in microsomes prepared from control or prostaglandin F2 alpha (PGF2 alpha)-treated rats. Activation was inhibited by the antioxidants, vitamin E and nordihydroguaiaretic acid, and by superoxide dismutase and catalase, which metabolize SOR and H2O2 to remove reactive oxygen species from the cell. The stimulation of PLA2 activity by xanthine oxidase was dependent upon the addition of calcium ions, and it was highest in samples in which cytosol was added to membranes. These results indicate that the SOR and/or H2O2 may mediate PLA2 activation, which may be involved in the luteolytic process.
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PMID:Stimulation of phospholipase A2 by xanthine oxidase in the rat corpus luteum. 133 74

Electrochemical sensors based on immobilised cytochrome c or superoxide dismutase for the measurement of superoxide radical production by stimulated neutrophils are described. Cytochrome c was immobilised covalently at a surface-modified gold electrode and by passive adsorption to novel platinised activated carbon electrodes (PACE). The reoxidation of cytochrome c at the electrode surface upon reduction by superoxide was monitored using both xanthine/xanthine oxidase and stimulated neutrophils as sources of the free radical. In addition, bovine Cu/Zn superoxide dismutase was immobilised to PACE by passive adsorption and superoxide, generated by xanthine/xanthine oxidase, detected by oxidation of hydrogen peroxide produced by the enzymic dismutation of the superoxide radical. A biopsy needle probe electrode based on cytochrome c immobilised at PACE and suitable for continuous monitoring of free radical production was constructed and characterised.
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PMID:Electrochemical sensors for direct reagentless measurement of superoxide production by human neutrophils. 133 38

On the basis of a recent report that minocycline is effective in the treatment of acne inflammation by acting directly as an antioxidant on infiltrating neutrophils, we investigated whether doxycycline might also be capable of reducing the generation of reactive oxygen species, using human neutrophils and a cell-free, xanthine-xanthine oxidase system. The species investigated are superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). Doxycycline significantly reduced the levels of O2-, H2O2 and OH. generated by both systems. Our results seem to suggest that the clinical effectiveness of doxycycline in the treatment of acne inflammation is due partly to its antioxidant effect on neutrophils.
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PMID:Effect of doxycycline on the generation of reactive oxygen species: a possible mechanism of action of acne therapy with doxycycline. 135 52

We determined the effects of superoxide anion, produced by addition of xanthine oxidase to hypoxanthine, on the intracellular pH (pHi) and intracellular free calcium concentration ([Ca2+]i) and release of arachidonate in human cultured amnion cells. Superoxide anion induced a prompt increase of pHi and subsequent increase of [Ca2+]i. The evoked pHi was inhibited by pretreatment with anion channel blockers but not affected by omission of extracellular Na+ or addition of amiloride. The increase of [Ca2+]i was inhibited significantly by the absence of extracellular calcium or by the addition of a calcium channel blocker, cobalt. NH4Cl, which can generally increase pHi, also increased [Ca2+]i of amnion cells. But the increase of [Ca2+]i induced by the NH4Cl was significantly less than that induced by the amount of superoxide anion causing a similar increase in pHi. These results show that superoxide anion, crossed through anion channel in membrane, increased [Ca2+]i at least partially via increase of pHi and that the calcium mobilization was dependent on both extracellular and intracellular sources. Superoxide anion induced the release of arachidonate in a dose-dependent manner and this induction was inhibited by omission of extracellular calcium. These data suggest that the release of arachidonate was dependent on the increase of [Ca2+]i. We also determined the viability of cells in the presence of superoxide anion by flow cytometry. Superoxide anion at the levels used in these experiments did not change the percentage of viable cells. These findings suggested that superoxide anion may regulate biological functions in amnion cells via pHi, [Ca2+]i mobilization, and the release of arachidonate without damaging the cells.
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PMID:Superoxide anion increases intracellular pH, intracellular free calcium, and arachidonate release in human amnion cells. 164 84

The effects of alpha-tocopherol, ascorbic acid and rutin on peroxidative processes were studied in xanthine-xanthine oxidase system, linoleic acid ufasomes and human erythrocyte membranes. In these three systems, tested compounds scavenge superoxide anion radicals or inhibit lipid peroxidation in a concentration-dependent manner, and it was shown that rutin was the most potent radical scavenger, followed by ascorbic acid and alpha-tocopherol. An important antilipoperoxidant activity was observed when these compounds were tested in combination, demonstrating that a dose-dependent interaction occurs. Water-soluble (rutin and ascorbic acid) as well as lipid-soluble (tocopherol) antioxidants are involved in the protection of polyunsaturated fatty acids constituting the ufasome or erythrocyte ghosts. When these compounds are used in combination, an additive effect is observed with alpha-tocopherol and ascorbic acid or rutin, while a supra-additive effect (synergism) is noted with ascorbic acid and rutin. Results obtained with the triple combination alpha-tocopherol-ascorbic acid-rutin show that an increase in superoxide radical scavenging activities or in lipid peroxidation inhibition is possible after the addition of a third antioxidant, as compared with the protective effects produced by the double combination of these compounds. This interaction takes place not only in homogeneous aqueous solutions, but also in ufasome or erythrocyte ghost preparations. It is suggested that ascorbic acid and rutin interacts with tocopherol at the surface of or the interface with the membrane, and that rutin simultaneously interacts with ascorbic acid.
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PMID:Additional antilipoperoxidant activities of alpha-tocopherol and ascorbic acid on membrane-like systems are potentiated by rutin. 165 40


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