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)

Na-Ca exchange activity in bovine cardiac sarcolemmal vesicles was stimulated up to 10-fold by preincubating the vesicles with 1 microM FeSO4 plus 1 mM dithiothreitol (DTT) in a NaCl medium. The increase in activity was not reversed upon removing the Fe and DTT. Stimulation of exchange activity under these conditions was completely blocked by 0.1 mM EDTA or o-phenanthroline; this suggests that the production of reduced oxygen species (H2O2, O2-.,.OH) during Fecatalyzed DTT oxidation might be involved in stimulating exchange activity. In agreement with this hypothesis, the increase in exchange activity in the presence of Fe-DTT was inhibited 80% by anaerobiosis and 60% by catalase. H2O2 (0.1 mM) potentiated the stimulation of Na-Ca exchange by Fe-DTT under both aerobic and anaerobic conditions; H2O2 also produced an increase in activity in the presence of either FeSO4 (1 microM) or DTT (1 mM), but it had no effect on activity by itself. Superoxide dismutase did not block the effects of Fe-DTT on exchange activity; however, the generation of O2-. by xanthine oxidase in the presence of an oxidizable substrate stimulated activity more than 2-fold. Hydroxyl radical scavenging agents (mannitol, sodium formate, sodium benzoate) did not attenuate the stimulation of activity observed with Fe-H2O2. Exchange activity was also stimulated by the simultaneous presence of glutathione (GSH; 1-2 mM) and glutathione disulfide (GSSG; 1-2 mM). Neither GSH nor GSSG was effective by itself and either 0.1 mM EDTA or o-phenanthroline blocked the effects on transport activity of the combination of GSH + GSSG. Treatment of the GSH and GSSG solutions with Chelex ion-exchange resin to remove contaminating transition metal ions reduced (by 40%) the degree of stimulation observed with GSH + GSSG. Full stimulating activity was restored to the Chelex-treated GSH and GSSG solutions by the addition of 1 microM Fe2+; Cu2+ was less effective than Fe2+ whereas Co2+ and Mn2+ were without effect. In the presence of 1 microM Fe2+, GSH alone produced a slight increase in transport activity, but this was markedly enhanced by the addition of Chelex-treated GSSG. The results indicate that stimulation of exchange activity requires the presence of both a reducing agent (DTT, GSH, O-.2, or Fe2+) and an oxidizing agent (H2O2, GSSG, and perhaps O2) and that the effects of these agents are mediated by metal ions (e.g. Fe2+).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles. 300 82

The accumulation of lipoperoxide (LPO) is reported to occur in the organs of animals with endotoxemia, where it is accompanied by an activation of xanthine oxidase (XOD) and a depletion of superoxide dismutase (SOD). In the present study, three measures of preventing LPO accumulation, ie, prior treatment with a XOD inhibitor, exogenous supply of enzymatic scavengers, and supplementation with chemical quenchers, were investigated to determine how to improve the survival rate of rats with lethal endotoxemia. Thirty minutes after treatment with various doses of allopurinol, SOD, catalase (CAT), vitamin E (VE), and reduced glutathione (GSH), adult male Wistar rats were subjected to endotoxemia by an intraperitoneal injection of 0.4 mg/100 g of Escherichia coli endotoxin. Allopurinol did not improve survival rates, denoting a lower level of XOD and an almost normal level of SOD in the liver. SOD (9,000 U/100 g) with or without CAT (4,000 U/100 g) markedly increased the survival rate of rats, with complete inhibition of hepatic LPO accumulation and suppression of XOD activity. CAT alone had no salutary effects on survival rate or hepatic LPO. Large amounts of VE (100 mg/100 g) or GSH (50 mg/100 g) slightly suppressed the accumulation of LPO in the liver but had no effect on survival rate. In that exogenous SOD has been considered not to penetrate the cellular membrane because of its high molecular weight, the results suggest that the extracellular spaces are the site of SOD action. Lipid peroxidation of the biomembrane initiated by oxygen free radicals released into extra-cellular space from phagocytes may play an important role in the development of lethality in experimental endotoxemia.
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PMID:Inhibition of lipid peroxidation improves survival rate of endotoxemic rats. 302 69

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 role of nonprotein thiols (NPSH) in the enzymatic reduction of the nitro function in 2-nitroimidazoles (2-NI) has been investigated. The addition of NPSH has been shown previously to protect cells from the hypoxic cytotoxicity of 2-NI, whereas depletion of NPSH enhances the hypoxic cytotoxicity. In this report, we have investigated the effects of thiol depleting agents, N-ethylmaleimide (NEM) and diethyl maleate (DEM), on the enzymatic reduction of the nitro group. Cytosolic and microsomal fractions of rat hepatic tissue and xanthine oxidase were employed as sources of nitro reductases. Addition of NPSH caused an enhancement in the reduction of the nitro group of 2-NI; cysteine was significantly more effective than glutathione (GSH) in stimulating the enzymatic reduction. The reduction of the nitro function was decreased markedly in the presence of NEM or DEM. Addition of cysteine or GSH reversed the inhibition with NEM. Both NEM and DEM also attenuated the enhancement of reduction observed after the addition of NPSH. These results suggest that the addition of NPSH facilities the reduction of the nitro function to the reduced intermediates that may be inactivated by an excess of NPSH, whereas the depletion of NPSH allows the accumulation of the toxic nitro radicals causing increased cytotoxicity.
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PMID:Role of nonprotein thiols in enzymatic reduction of 2-nitroimidazoles. 333 46

In this study we sought to define the role of oxygen-derived free radicals during ischemia and reperfusion in the production of acute damage to the gastric mucosa of baboons. The protective effect of the xanthine oxidase inhibitor, allopurinol, the superoxide scavenger, superoxide dismutase (SOD), and a long-acting SOD-albumin was determined. Mucosal damage was evaluated using light and scanning electron microscopy. Evidence for oxidative insult to the gastric mucosa was sought by measuring tissue concentrations of reduced (GSH) and oxidized (GSSG) glutathione. Gastric mucosal blood flow was estimated using the microsphere technique. A similar pattern of tissue damage was found at the end of ischemia in all three groups. Thirty minutes after reperfusion, severe mucosal damage (grade 3) increased only in the untreated control. In the two treated groups, grade 3 damage remained unchanged during reperfusion and a decrease in the percentage of moderate damage (grade 2) was seen. Both GSH and GSSG tissue concentrations were lower in the untreated controls as compared to the scavenger-treated groups, making it questionable whether GSH/GSSG tissue levels adequately reflect oxidative stress. We conclude that in our ischemia-reperfusion model the generation of oxygen-derived free radicals produces mucosal damage and prevents the restitution of moderate mucosal damage during reperfusion. In ischemia, factors other than free radicals seem to be responsible for mucosal damage. The protective effect of allopurinol and SOD was not mediated by changes in gastric mucosal blood flow.
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PMID:Gastric mucosal lesions induced by hemorrhagic shock in baboons. Role of oxygen-derived free radicals. 337 79

The implication of activated oxygen in the interaction between hypoxic rat liver and circulating erythrocytes was investigated. Reduced species of oxygen generated in hypoxic liver owing to accelerated purine nucleotide degradation via xanthine oxidase initiate alterations of plasma membrane and glutathione system of erythrocytes. Osmotic fragility, hemolysis rate and erythrocytic GSSG:GSH ratio may be considered as appropriate indicators of oxidative load in liver and other tissues. Addition of erythrocytes to the perfusion medium attenuates the GSSG efflux of hypoxic liver from 2.7 +/- 0.5 nmol x g w.w.-1 x min-1 to 1.4 +/- 0.2 nmol x g w.w.-1 x min-1 Thus, circulating erythrocytes protect the liver against oxidative attack.
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PMID:Damage of erythrocytes by activated oxygen generated in hypoxic rat liver. 350 95

The biliary GSSG efflux rate of normoxic perfused rat liver was 1.5 +/- 0.2 nmol/min/g liver wet weight. The GSSG efflux rate as indicator for the flux through the glutathione peroxidase reaction and, therefore, for an oxidative loading increased with the extent of hypoxia. 2.6 +/- 0.5 nmol/min/g were released from the severely hypoxic liver. The hydroxyl radical scavenger formate as well as the xanthine oxidase inhibitor allopurinol reduced the efflux rate of GSSG. GSH was released from the perfused liver at a rate of 15.5 nmol/min/g which was nearly unchanged in severe hypoxia. The high rate of glucose liberation from the hypoxic liver declined to almost that of the normoxic organ in the presence of formate. There is an 'oxidative stress' during hypoxic liver perfusion which probably originates from increased generation of activated oxygen species in the degradation of purine nucleotides.
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PMID:Formation of activated oxygen in the hypoxic rat liver. 383 24

1. The aerobic oxidation of GSH and other thiols by rat liver homogenate is abolished either by previous dialysis or by removal of the proteins but is restored by a mixture of the protein-free filtrate and the dialysed homogenate. 2. The oxidation is prevented by previously heating the dialysed homogenate but not the protein-free filtrate and also by known inhibitors of xanthine oxidase. 3. A similar oxidation occurs with hypoxanthine in place of of protein-free filtrate.
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PMID:The enzymic oxidation of glutathione in rat liver homogenates. 545 14

1. The aerobic loss of GSH added to the supernatant fraction from rat liver is much increased by including the microsome fraction, which both inhibits the concurrent reduction of the GSSG formed and also augments the net oxidation rate. 2. Oxidation occurs with a mixture of dialysed supernatant and a protein-free filtrate; the latter is replaceable by hypoxanthine and the former by xanthine oxidase, whereas fractions lacking this enzyme give no oxidation. 3. In all these instances augmentation occurs with microsomes, with fractions having urate oxidase activity and with the purified enzyme; uric acid and microsomes alone also support the oxidation. 4. Evidence implicating additional protein factors is discussed. 5. It is suggested that GSH oxidation by homogenate is linked through glutathione peroxidase to the reaction of endogenous substrate with supernatant xanthine oxidase and of the uric acid formed with peroxisomal urate oxidase.
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PMID:The function of subcellular fractions in the oxidation of glutathione in rat liver homogenate. 545 15

The initial metabolite formed by most mammalian nitroreductases is the nitro anion free radical. We, as well as others, have proposed that nitroheterocyclic anion radicals covalently bind to protein, DNA, or thiol compounds such as reduced glutathione (GSH). Our results indicate that even at 100 mM GSH does not affect the steady-state concentration of the nitro anion free radical of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide (NFTA) in rat hepatic microsomal or xanthine oxidase incubations. The steady-state ESR amplitude of the anion radical is also unchanged by the addition of BSA or DNA. Similar results are obtained with nitrofurazone and nitrofurantoin. The reactive chemical species which binds to tissue macromolecules and GSH upon the reduction of nitrofurans remains unknown, but the anion free radical metabolite can be excluded from consideration.
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PMID:No detectable reaction of the anion radical metabolite of nitrofurans with reduced glutathione or macro-molecules. 609 28


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