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)

Lesion formation due to oral administration of absolute ethanol could be prevented by parenteral pretreatment with antiperoxidative drugs such as butylated hydroxytoluene (BHT), quercetin and quinacrine. Also effective were allopurinol and oxypurinol, inhibitors of xanthine oxidase, but not superoxide dismutase (SOD) and hydroxyl radical scavengers, such as sodium benzoate and dimethyl sulfoxide (DMSO). BHT, quercetin, quinacrine and sulfhydryl compounds such as reduced glutathione and cysteamine which offer gastroprotection in vivo against ethanol inhibited lipid peroxidation induced in vitro by ferrous ion in porcine gastric mucosal homogenate, but SOD, sodium benzoate, DMSO, allopurinol and oxypurinol did not. These results suggest the possibility that an active species, probably derived from free iron mobilized by the xanthine oxidase system, other than oxygen radicals such as hydroxyl radicals, contributes to lipid peroxidation and lesion formation in the gastric mucosa after absolute ethanol administration.
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PMID:Effect of antiperoxidative drugs on gastric damage induced by ethanol in rats. 361 39

Molybdenum cofactor (mocofactor) is extracted efficiently, free of impurities and in high concentrations, by acid treatment of xanthine oxidase and subsequent incubation of the precipitate with phosphate buffer containing EDTA, molybdate and oxygen. It is suggested that cofactor is bound to the enzyme via hydrophobic forces as well as via an oxygen-sensitive mechanism. Upon extraction, the capability to complement the apo nitrate reductase of Neurospora crassa nit-1 can be conserved only in the total absence of oxygen. Cysteine and glutathione were shown to protect efficiently free mocofactor from oxidation. Two species of active mocofactor, probably a molybdoform and a demolybdoform, could be separated by means of reversed-phase HPLC with a mobile phase of 5 mM sodium citrate at a pH of 6.5. The mode of interaction between either of these species with thiol reagents is discussed.
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PMID:Extraction and purification of molybdenum cofactor from milk xanthine oxidase. 369 96

Isolated erythrocyte membranes exposed to protease-free xanthine oxidase plus xanthine and ferric iron undergo lipid peroxidation and protein crosslinking (appearance of high molecular weight aggregates on sodium dodecyl sulfate (SDS) gel electrophoresis). Spectrin is more susceptible to crosslinking than the other polypeptides. Thiol-reducible bonds (disulfides) as well as nonreducible bonds are generated, the former type relatively rapidly (detected within 10-20 min) and the latter type more slowly (usually detected after 1 h). Reducible crosslinking is inhibited by catalase, but not by superoxide dismutase, desferrioxamine, butylated hydroxyltoluene, and mannitol; whereas nonreducible crosslinking, like free radical lipid peroxidation, is inhibited by all of these agents except mannitol. Zinc(II) also inhibits lipid peroxidation, but stimulates disulfide bond formation to the virtual exclusion of all other crosslinking. Our results indicate that disulfide formation is dependent on H2O2, but not O2- or iron. However, O2-, H2O2, and iron are all required for lipid peroxidation and nondisulfide crosslinking, suggesting the intermediacy of OH generated via the iron-catalyzed Haber-Weiss reaction. The possible role of malonaldehyde (MDA, a by-product of lipid peroxidation) in the latter type of crosslinking was examined. Solubilized samples of xanthine/xanthine oxidase-treated membranes showed a strong visible fluorescence (emission maximum 450 nm; excitation 390 nm). This resembled the fluorescence of membranes treated with authentic MDA, which forms conjugated imine linkages between amino groups. Fluorescence scanning of SDS gels from MDA-treated membranes showed a strong signal coincident with crosslinked proteins and also one in the low molecular weight, nonprotein region, suggestive of aminolipid conjugates. Similar scanning on xanthine/xanthine oxidase-reacted membranes indicated that all fluorescence is associated with the lipid fraction. Thus, nonreducible protein crosslinks in this system do not appear to be of the MDA-derived, Schiff base type.
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PMID:Xanthine oxidase-catalyzed crosslinking of cell membrane proteins. 380 Mar 91

The luminol-dependent chemiluminescence (CL) response in vitro of guinea-pig C. parvum-activated peritoneal macrophages to platelet activating factor (PAF) has been compared with that to opsonized zymosan (OpZ). The response to PAF (5 X 10(-6) mol/l.) reached a peak within 1 min, that to OpZ (0.17 mg/ml) within 10-20 min. Peak responses to both stimuli were dose-dependently inhibited in a similar manner by p-hydroxymercuribenzoate (10(-5) - 10(-3) mol/l), sodium benzoate (10(-5) - 10(-3) mol/l.) and quinacrine (10(-6) - 10(-3) mol/l.). In contrast, the xanthine oxidase inhibitor allopurinol (IC50 vs OpZ, 220 mumol/l.; vs PAF greater than 1000 mumol/l.), the methylation-inhibiting combination homocysteine + 3-deazaadenosine (IC50 vs OpZ, 22 mumol/l.; vs PAF greater than 100 mumol/l.), the phospholipase A2 inhibitor and alkylating agent p-bromophenacylbromide (pBPB; IC50 vs OpZ, 2.6 mumol/l.; vs PAF 15 mumol/l.) and the beta-adrenoceptor agonist isoprenaline (IC50 vs OpZ, 0.1 mumol/l.; PAF greater than 10 mumol/l.) all exerted differential inhibitory effects on the CL responses to the two stimuli, though colour quenching by adrenochrome cannot be ruled out in the differential effect of isoprenaline. In screening studies, carried out with CL responses measured 2 or 5 min after PAF and OpZ, respectively, verapamil (less than or equal to 10(-4) mol/l.), trifluoperazine (less than or equal to 10(5) mol/l.) EDTA (less than or equal to 10(6) mol/l.), mannitol (less than or equal to 10(-2) mol/l.), metyrapone (less than or equal to 10(-5) mol/l.), SQ 22536 (less than or equal to 10 micrograms/ml.), iso-butyl methylxanthine (less than or equal to 10(-5) mol/l.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological analysis of guinea-pig macrophage chemiluminescence responses to platelet activating factor and opsonized zymosan. 380 36

The presence of antigenically active xanthine oxidase was indicated in various relatively purified preparations of sulfhydryl oxidase obtained from bovine milk. Evidence for formation of a complex of the two enzymes was obtained by double immunodiffusion. Furthermore, sodium dodecylsulfate-gel electrophoresis of sulfhydryl oxidase and xanthine oxidase model mixtures indicated that high molecular weight species were present that reacted with both antisulfhydryl oxidase and antixanthine oxidase. Similar gel electrophoretic patterns visualized by protein-dye binding methods revealed a distinct band (greater than 200 kdalton) was formed upon incubation of mixtures of the two enzymes, the presence of which was unaffected by reduction of protein disulfide bonds. Immunofluorescent staining techniques showed both enzymes in the apical plasma membrane. Because sulfhydryl oxidase previously has been shown to catalyze conversion of the dehydrogenase form of xanthine oxidase to the oxidase form, this conversion may occur when xanthine oxidase contacts sulfhydryl oxidase in the apical plasma membrane. This conversion and the resulting potential for production of active oxygen species could be significant to membranotropic processes, such as fat globule secretion, and to the oxidative stability of the milk fat globule membrane.
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PMID:Association of sulfhydryl oxidase and xanthine oxidase in bovine mammary tissue. 380 56

[3H]1-Nitropyrene was administered at a dose of 25 mg/kg by i.p. injection to female Wistar rats. Animals were killed 24 h later and DNA was isolated from kidney, liver and mammary gland, enzymically hydrolysed and analysed by reverse-phase h.p.l.c. A major adduct peak was detected in DNA from each of the three organs. Enzymic hydrolysates of DNA, which had been reacted in vitro with 1-nitropyrene in the presence of xanthine oxidase, were similarly analysed by h.p.l.c. One major adduct peak was obtained which had the same retention time as the in vivo product. Confirmatory evidence that the in vivo adduct and the in vitro adduct were structurally similar was obtained from the determination of the pH-dependent solvent partitioning profiles. Further, treatment of the in vivo adduct from liver, kidney or mammary gland DNA hydrolysates and the in vitro adduct with sodium hydroxide resulted in the formation of a more polar product which eluted earlier on h.p.l.c. This behaviour is consistent with scission of the imidazole ring of a deoxyguanosine adduct. The major DNA adduct formed in vitro following xanthine oxidase reduction of 1-nitropyrene has previously been identified by others as N-(deoxyguanosin-8-yl)-1-aminopyrene. The present data suggest that the in vivo 1-nitropyrene-DNA adduct has the same structure.
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PMID:Evidence for N-(deoxyguanosin-8-yl)-1-aminopyrene as a major DNA adduct in female rats treated with 1-nitropyrene. 383 6

We studied the effects of vitamin C (sodium ascorbate) on the genotoxicity of oxygen radicals to tissue culture cells. Chinese hamster ovary cells (CHO cells), when exposed to an enzymatic oxygen radical generating system (xanthine oxidase plus hypoxanthine), develop increased numbers of sister-chromatid exchanges (SCEs). Inclusion of ascorbate in these incubations resulted in significant, but variable effects. In some cases, ascorbate (less than 0.1 mM) was protective and fewer SCEs were produced. In others, significant augmentation of oxygen radical-induced SCEs occurred. These experiments illustrate the complexity of the interactions of ascorbate in biologic systems and the difficulty of predicting a desirable or harmful effect.
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PMID:The effect of vitamin C on oxygen radical-induced sister-chromatid exchanges. 383 99

Incubation of rat brain synaptosomes with xanthine and xanthine oxidase (X/XO) resulted in an inhibition of gamma-aminobutyric acid (GABA) uptake. The inhibitory effects of X/XO were temperature- and time-dependent, and were characterized by an increased Km for GABA and a decreased Vmax. Inhibition of GABA uptake by X/XO was associated with both the formation of malonyldialdehyde (MDA) and conjugated dienes, indicating that lipid peroxidation was involved. Studies with catalase, superoxide dismutase (SOD), mannitol, and chelated iron suggested that hydroxyl radical (OH X) was probably responsible for the initiation of lipid peroxidation. Both the peroxidation of synaptosomal membranes and the inhibition of GABA uptake by X/XO were enhanced by the addition of ADP and FeCl2. The X/XO-induced inhibition of GABA uptake by synaptosomes could be prevented by preincubation of synaptosomes with certain glucocorticoids prior to X/XO exposure. Methylprednisolone sodium succinate (MPSS), dexamethasone sodium phosphate (DMSP), and prednisolone sodium succinate (PSS) all prevented the inhibition of GABA uptake by X/XO. MPSS was most effective at concentrations around 100 microM, DMSP was slightly more potent, and PSS was optimal at around 300 microM. On the other hand, hydrocortisone sodium succinate (HCSS) was ineffective at preventing X/XO-induced inhibition of GABA uptake at concentrations up to 3 mM. The steroids are presumed to work through a mechanism that blocked the formation of lipid peroxides, as MPSS inhibited the formation of conjugated dienes in synaptosomes exposed to X/XO at a concentration that also protected GABA uptake.
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PMID:Lipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomes: protection by glucocorticoids. 388 88

The milk-fat-globule membrane (MFGM) was isolated from guinea-pig milk and the membrane-associated proteins and glycoproteins characterized by electrophoretic techniques. Major components of the membrane included PAS-I, a sialoglycoprotein of Mr greater than or equal to 200000, the redox enzyme xanthine oxidase and the glycoprotein, butyrophilin. Membrane preparations also contained two other glycoproteins, GP-80 and GP-55, of Mr 80000 and 55000, respectively. Comparison of guinea-pig xanthine oxidase and butyrophilin with proteins from bovine MFGM by peptide mapping procedures, showed that the two proteins in both species were similar, but not identical. GP-55 may also be related to glycoproteins of Mr 45000 and 48000 in the bovine membrane. The integral and peripheral components of guinea-pig MFGM were identified by treating membrane preparations with sodium carbonate solutions at high pH and by partitioning the membrane proteins in solutions of Triton X-114. By these criteria xanthine oxidase and GP-55 appeared to be peripheral components and GP-80 an integral protein of the membrane. PAS-I and butyrophilin displayed hydrophilic properties in Triton X-114 solutions, but could not be removed from membrane preparations with sodium carbonate. Possible reasons for these ambiguous data are discussed. The observed similarity between several of the proteins of guinea-pig and bovine MFGM implies that these proteins may have specific functions related to milk secretion in mammary tissue, e.g. in the budding of milk-fat globules or the exocytosis of milk protein and lactose at the apical surface.
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PMID:Identification and characterization of the principal proteins of the fat-globule membrane from guinea-pig milk. 402 34

The composition of milk xanthine oxidase has been reinvestigated. When the enzyme is prepared by methods that include a selective denaturation step in the presence of sodium salicylate the product is obtained very conveniently and in high yield, and is homogeneous in the ultracentrifuge and in recycling gel filtration. It has specific activity higher than previously reported preparations of the enzyme and its composition approximates closely to 2mol of FAD, 2g-atoms of Mo and 8g-atoms of Fe/mol of protein (molecular weight about 275000). In contrast, when purely conventional preparative methods are used the product is also homogeneous by the above criteria but has a lower specific activity and is generally comparable to the crystallized enzyme described previously. Such samples also contain 2mol of FAD/mol of protein but they have lower contents of Mo (e.g. 1.2g-atom/mol). Amino acid compositions for the two types of preparation are indistinguishable. These results confirm the previous conclusion that conventional methods give mixtures of xanthine oxidase with an inactive modification of the enzyme now termed ;de-molybdo-xanthine oxidase', and show that salicylate can selectively denature the latter. The origin of de-molybdo-xanthine oxidase was investigated. FAD/Mo ratios show that it is present not only in enzyme purified by conventional methods but also in ;milk microsomes' (Bailie & Morton, 1958) and in enzyme samples prepared without proteolytic digestion. We conclude that it is secreted by cows together with the active enzyme and we discuss its occurrence in the preparations of other workers. Studies on the milks of individual cows show that nutritional rather than genetic factors determine the relative amounts of xanthine oxidase and de-molybdo-xanthine oxidase. A second inactive modification of the enzyme, now termed ;inactivated xanthine oxidase', causes variability in activity relative to E(450) or to Mo content and formation of it decreases these ratios during storage of enzyme samples including samples free from demolybdo-xanthine oxidase. We conclude that even the best purified xanthine oxidase samples described here and by other workers are contaminated by significant amounts of the inactivated form. This may complicate the interpretation of changes in the enzyme taking place during the slow phase of reduction by substrates. Attempts to remove iron from the enzyme by published methods were not successful.
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PMID:The composition of milk xanthine oxidase. 544 74


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