UNIPROT:P47989 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

1. The survival of mammalian epithelial cells exposed in vitro to the xanthine/xanthine oxidase system in phosphate-buffered saline (PBS) or serum-containing medium (SCMEM) was investigated. 2. The cytotoxic effect observed depended on the composition of the medium in which the enzymic reaction was carried out; a surviving fraction of 5 x 10(-5) was found for cells exposed in PBS and 5.2 x 10(-1) for those in SCMEM. 3. The cytotoxic product(s) formed by the xanthine/xanthine oxidase system was relatively stable in PBS; survival of cells incubated after completion of the enzymic reaction was always less than that found for cells exposed during the reaction in the same system. 4. Superoxide dismutase or mannitol present during the enzymic reaction did not inhibit the cytotoxic effect. 5. NaN3 (a single-oxygen quencher and a catalase inhibitor) added to the system in SCMEM caused a reduction in survival to the level observed for cells exposed to the enzymic reaction in PBS. 6. Catalase completely protected cells, but no protection was observed when both catalase and NaN3 were present in the reaction mixture. 7. A similar cytotoxic effect was produced when cells were treated with H2O2 alone. 8. The rate of H2O2 decomposition in medium was accelerated by the presence of serum, but this was completely inhibited by NaN3. 9. It is concluded that H2O2 is the major cytotoxic product formed by the xanthine/xanthine oxidase system.
...
PMID:Role of hydrogen peroxide in the cytotoxicity of the xanthine/xanthine oxidase system. 282 57

It has been proposed that oxygen free radical production is an important mediator of the myocardial dysfunction during the course of acute ischemia. We tested this hypothesis by characterizing the pathway of calcium efflux across sarcoplasmic reticulum (SR) membranes affected by oxygen free radicals. The effect of oxygen free radicals on the steady state calcium load, calcium permeability, and Ca,Mg-ATPase activity of isolated canine cardiac SR vesicles was investigated at pH 7.0. In vitro generation of oxygen free radicals by xanthine oxidase (0.09 units/ml), acting on xanthine in doses up to 50 microM as a substrate, increased the permeability of the SR vesicles to calcium, determined by measuring net efflux of calcium after stopping pump-mediated fluxes, and decreased total intravesicular calcium and free intravesicular calcium with no effect on Ca,Mg-ATPase activity. The effect of oxygen free radicals on calcium permeability was calcium gradient-dependent. Xanthine alone or xanthine plus denatured xanthine oxidase had no effect on this system. Superoxide dismutase (SOD, 56 units/ml), but not denatured SOD, significantly inhibited the effect of xanthine-xanthine oxidase reaction. The calcium permeability of the SR membrane decreased with decreasing calcium load. In addition, inasmuch as extravesicular calcium exerts only a slight effect on calcium permeability, the decrease in the permeability with calcium load is specifically related to the calcium load. Oxygen free radical-induced increase in calcium permeability was unaffected by Mg concentration between 2.1 and 21 mM. In summary, our data reveal that .O2- can produce a diminished level of accumulated calcium, which is reflected by the decreased calcium load and an increase in passive calcium permeability, and that the decreased calcium accumulation in the presence of the xanthine-xanthine oxidase system may not be mainly due to an inhibited calcium pump but due to an increased calcium permeability. Our results also suggest that increased SR membrane passive calcium permeability induced by oxygen free radicals is not carrier mediated. It is postulated that, with the oxygen free radical-mediated progressive increase in calcium permeability, free cytosolic calcium concentrations would increase in ischemic myocardium.
...
PMID:The effect of oxygen free radicals on calcium permeability and calcium loading at steady state in cardiac sarcoplasmic reticulum. 284 52

The generation of superoxide radicals from xanthine oxidase-hypoxanthine in a particulate fraction of gerbil cerebral cortex influenced the activity of the synaptic enzyme adenylate cyclase, as well as Mn2+- and Na+,K+-sensitive forms of ATPase. Low concentrations of xanthine oxidase actually elevated the sensitivity of adenylate cyclase to GTP, GTP + norepinephrine (NE), and forskolin but not significantly to Mn2+. Higher levels of xanthine oxidase elicited a marked inhibition of these responses. The stimulation of adenylate cyclase mechanisms requiring GTP (GTP, forskolin, and NE) was more susceptible than was Mn2+, suggesting that the guanine nucleotide stimulatory protein was more vulnerable to free radical attack than the catalytic site of adenylate cyclase. Superoxide dismutase (SOD), but not catalase, partially protected the forskolin-sensitive enzyme from the action of xanthine oxidase-hypoxanthine. A combination of SOD plus catalase preserved enzyme responses to forskolin. In comparison, additions of SOD plus mannitol or catalase plus flunarizine were less effective. The sensitivity of the particulate ATPase to Mn2+ was more labile to the consequence of superoxide formation than Na+, K+ -ATPase. In this regard the Ca2+,Mg2+ sensitivity of the enzyme was reduced only to a marginal extent. The findings might be analogous to in vivo data in which cerebral adenylate cyclase and Na+, K+-ATPase are damaged following postischemic reperfusion in gerbils, a process thought to be mediated by free radicals.
...
PMID:Free radicals generated by xanthine oxidase-hypoxanthine damage adenylate cyclase and ATPase in gerbil cerebral cortex. 285 Apr 58

Oxygen-free radicals have been implicated as mediators of ischemic damage in a number of tissues, including heart, kidney, small intestine, and skin. Superoxide dismutase, a free radical scavenger, and allopurinol, an inhibitor of xanthine oxidase (a catalyst in the formation of superoxide) have been shown separately to decrease ischemic damage to tissue. Sixty-two male Sprague-Dawley rats (220 to 280 g) were divided into five groups: control, superoxide dismutase only, allopurinol only, high-dose combined allopurinol and superoxide dismutase, and low-dose combined allopurinol and superoxide dismutase. An 18-cm2 ventral island skin flap, based on a single inferior epigastric vessel, was raised and replaced. Blood flow was assessed with a perfusion fluorometer immediately after the flap was replaced, and on postoperative days 1 and 3. Gross necrosis was assessed on postoperative day 7. Gross necrosis was reliably reduced in all groups as compared with the control; however, necrosis in any one experimental group was not significantly different from any other experimental group. Necrosis (expressed as a percentage of the area of the random [distal] half of the flap) was as follows for each group: control, 74%; superoxide dismutase, 43%; allopurinol, 43%; high-dose combined, 48%; low-dose combined, 33%. Blood flow, as represented by the dermofluorescence index, was not changed by any of the treatments. Blood flow was also related to the eventual survival or necrosis for any one portion of tissue. All experimental groups survived with significantly less blood flow than the control.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The effects of allopurinol and superoxide dismutase in a rat model of skin flap necrosis. 291 92

It has been postulated that changes in the availability of partially reduced O2 species, such as O2 radicals, could serve as a link between PO2 in the alveolus and pulmonary vascular tone (Herz 11: 127-141, 1986). To assess this hypothesis, the hemodynamic effects of acute changes in the balance between the production of O2 radicals and availability of antioxidant enzymes were studied in the isolated perfused rat lung. Intravascular generation of O2 radicals, by administration of xanthine-xanthine oxidase, decreased the pulmonary vascular pressor response to alveolar hypoxia (-55 +/- 5%) and angiotensin II (-58 +/- 10%, P less than 0.01 for each) in isolated perfused rat lungs without increasing the lung wet-to-dry weight ratio. Decreases in pulmonary vascular reactivity were inhibited by pretreatment of the lung with desferrioxamine or a mixture of catalase and superoxide dismutase. Catalase and superoxide dismutase preserved the hypoxic pressor response whether given in liposomes or in dissolved form. Superoxide dismutase administered free in solution, or combined with catalase in liposomes, increased the normoxic pulmonary arterial pressure and enhanced vascular reactivity to angiotensin II and hypoxia. Lungs treated with antioxidant enzymes in liposomes had 50% higher lung catalase levels than control lungs (P less than 0.05). These findings demonstrate that exogenous partially reduced O2 species can decrease pulmonary vascular reactivity and suggest that endogenous radicals, superoxide radical in particular, might be important in modulating pulmonary vascular tone.
...
PMID:Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung. 291 13

The selenium-containing glutathione peroxidase, when in its active reduced form, was inactivated during exposure to the xanthine oxidase reaction. Superoxide dismutase completely prevented this inactivation, whereas catalase, hydroxyl radical scavengers, or chelators did not, indicating that O2 was the responsible agent. Conversion of GSH peroxidase to its oxidized form, by exposure to hydroperoxides, rendered it insensitive toward O2. The oxidized enzyme regained susceptibility toward inactivation by O2 when reduced with GSH. The inactivation by O2 could be reversed by GSH; however, sequential exposure to O2 and then hydroperoxides caused irreversible inactivation. Reactivity toward CN- has been used as a measure of the oxidized form of GSH peroxidase, whereas reactivity toward iodoacetate has been taken as an indicator of the reduced form. By these criteria both O2 and hydroperoxides convert the reduced form to oxidized forms. A mechanism involving oxidation of the selenocysteine residue at the active site has been proposed to account for these observations.
...
PMID:Inactivation of glutathione peroxidase by superoxide radical. 299 78

The N-oxidation of N-(2-methyl-1-phenyl-2-propyl)hydroxylamine (N-hydroxyphentermine, MPPNHOH) and the N-hydroxylation of 2-methyl-1-phenyl-2-propylamine (phentermine) by reconstituted systems that contained cytochromes P-450 purified from rat liver microsomes were demonstrated. The oxidation of MPPNHOH, but not of phentermine, could also be mediated by a superoxide and hydrogen peroxide generating system that contained xanthine and xanthine oxidase. Superoxide dismutase completely inhibited the oxidation of MPPNHOH by the xanthine/xanthine oxidase system and inhibited by 70% the oxidation mediated by a reconstituted cytochrome P-450 oxidase system. The majority of the microsomal oxidation was inhibited by an antibody raised against the major isozyme of cytochrome P-450 purified from livers of phenobarbital-pretreated rats. 2-Methyl-2-nitroso-1-phenylpropane (MPPNO) was found to be an intermediate in the overall oxidation of MPPNHOH to 2-methyl-2-nitro-1-phenylpropane (MPPNO2). Superoxide dismutase appeared to inhibit the first step, the conversion of MPPNHOH to MPPNO. These observations are accounted for by a sequence of two mechanistically distinct P-450-mediated oxidations. In the first reaction, N-hydroxylation of phentermine occurs by a normal cytochrome P-450 pathway. The formed hydroxylamine then uncouples the cytochrome P-450 system to generate superoxide and hydrogen peroxide. The superoxide oxidizes MPPNHOH to MPPNO which is then oxidized to MPPNO2, the ultimate product. This superoxide-mediated oxidation represents another pathway for N-oxidation by cytochrome P-450.
...
PMID:Role of superoxide in the N-oxidation of N-(2-methyl-1-phenyl-2-propyl)hydroxylamine by the rat liver cytochrome P-450 system. 299 91

3 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.50) from Pseudomonas testosterone was inactivated by superoxide radicals generated by the aerobic xanthine oxidase reaction. Superoxide dismutase, NAD+, bovine serum albumin and histidine and cysteine as free amino acids partially protected the enzyme from inactivation. NADH-binding properties were determined by fluorescence spectroscopy, and no variation was found between native enzyme and the unmodified fraction of the partly inactivated one. The fluorescence emission maximum for the completely inactivated enzyme was shifted 10 nm to a longer wavelength when compared with the native one, and it seems possible that the modification of histidine and cysteine residues by superoxide radicals causes the conformational change of the enzyme and the consequent loss of catalytic activity.
...
PMID:Inactivation of 3 alpha-hydroxysteroid dehydrogenase by superoxide radicals. Modification of histidine and cysteine residues causes the conformational change. 300 70

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)
...
PMID:Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles. 300 82

Human polymorphonuclear leucocytes were found to promote peroxidation of phospholipid liposomes upon stimulation by phorbol myristate acetate. Peroxidation required the presence of either pyrophosphate-chelated or ADP-chelated iron, whereas iron chelated to EDTA or ATP had no effect. Peroxidation was also catalyzed by ferritin, but not by transferrin. Superoxide dismutase abolished the peroxidation, whereas catalase and apparently also the hydroxyl radical scavenger dimethyl sulphoxide were inactive, indicating that the peroxidation was mediated by superoxide radicals but not by hydrogen peroxide or hydroxyl radicals. Xanthine oxidase-promoted peroxidation was studied for comparison and showed similar characteristics except that transferrin catalyzed the peroxidation. Peroxidation of membrane lipids may be a mechanism whereby granulocytes cause tissue damage in inflammation. The drugs paracetamol, gentisic acid and 5-aminosalicylic acid inhibited lipid peroxidation, probably through their ability to react with the superoxide anion.
...
PMID:Peroxidation of liposomes promoted by human polymorphonuclear leucocytes. 301 66

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>