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 peroral administration of xylitol on the absorption of iron and the activities of xanthine oxidase (EC 1.2.3.2) and ferroxidase in rat duodenal wall was studied. Adult male rats were given the basal diet containing 200 g xylitol/kg or the same diet containing no added carbohydrates for 8 weeks. Both feeding groups comprised twelve animals. Xylitol significantly increased serum and liver Fe concentrations with a concomitant, significant increase in the duodenal xanthine oxidase activities, but caused a marginal increase in the duodenal ferroxidase activities. In vitro, sugar alcohols reduced the binding rate of Fe to transferrin. The xylitol-induced increase of Fe absorption may involve the following mechanism: the high intraluminal xylitol concentration of the xylitol-fed rats keeps Fe in the form of a soluble complex for a prolonged period of time, due to the slow absorption of xylitol. The polyol-Fe complex in turn induces xanthine oxidase and ferroxidase formation.
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PMID:Duodenal xanthine oxidase (EC 1.2.3.2) and ferroxidase activities in the rat in relation to the increased iron absorption caused by peroral xylitol. 384 Jun 96

The effect of transferrins on hydroxyl radical formation from the superoxide anion and hydrogen peroxide generated by the xanthine-xanthine oxidase system has been studied by EPR using 5,5-dimethyl-1-pyrroline N-oxide as a spin trap. Neither diferriclactoferrin nor diferrictransferrin were found capable of promoting hydroxyl radical formation via the Haber-Weiss reaction even in the presence of EDTA in concentrations up to 1 mM. Activity observed by other authors may have been due to the presence of extraneous iron or an active protein impurity. Partially saturated transferrin and lactoferrin present in normal subjects may protect cells from damage by binding iron that might catalyze hydroxyl radical formation from superoxide and hydrogen peroxide. In any event, the hydroxyl radical formation observed in active neutrophils during phagocytosis cannot be associated with lactoferrin activity.
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PMID:The effect of human serum transferrin and milk lactoferrin on hydroxyl radical formation from superoxide and hydrogen peroxide. 609 75

The ability of paraquat radicals (PQ+.) generated by xanthine oxidase and glutathione reductase to give H2O2-dependent hydroxyl radical production was investigated. Under anaerobic conditions, paraquat radicals from each source caused chain oxidation of formate to CO2, and oxidation of deoxyribose to thiobarbituric acid-reactive products that was inhibited by hydroxyl radical scavengers. This is in accordance with the following mechanism derived for radicals generated by gamma-irradiation [H. C. Sutton and C. C. Winterbourn (1984) Arch. Biochem. Biophys. 235, 106-115] PQ+. + Fe3+ (chelate)----Fe2+ (chelate) + PQ++ H2O2 + Fe2+ (chelate)----Fe3+ (chelate) + OH- + OH.. Iron-(EDTA) and iron-(diethylenetriaminepentaacetic acid) (DTPA) were good catalysts of the reaction; iron complexed with desferrioxamine or transferrin was not. Extremely low concentrations of iron (0.03 microM) gave near-maximum yields of hydroxyl radicals. In the absence of added chelator, no formate oxidation occurred. Paraquat radicals generated from xanthine oxidase (but not by the other methods) caused H2O2-dependent deoxyribose oxidation. However, inhibition by scavengers was much less than expected for a reaction of hydroxyl radicals, and this deoxyribose oxidation with xanthine oxidase does not appear to be mediated by free hydroxyl radicals. With O2 present, no hydroxyl radical production from H2O2 and paraquat radicals generated by radiation was detected. However, with paraquat radicals continuously generated by either enzyme, oxidation of both formate and deoxyribose was measured. Product yields decreased with increasing O2 concentration and increased with increasing iron(DTPA). These results imply a major difference in reactivity between free and enzymatically generated paraquat radicals, and suggest that the latter could react as an enzyme-paraquat radical complex, for which the relative rate of reaction with Fe3+ (chelate) compared with O2 is greater than is the case with free paraquat radicals.
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PMID:Hydroxyl radical production from hydrogen peroxide and enzymatically generated paraquat radicals: catalytic requirements and oxygen dependence. 609 5

The nonceruloplasmin enzyme located in the intestinal mucosa which promotes the incorporation of iron into transferrin has been resolved into a small, heat-stable component and a heat-labile protein component. The small, heat-stable component was purified from the high-speed supernatant of intestinal mucosal homogenates by ion-exchange chromatography and gel filtration and identified as xanthine. The heat labile protein component was purified from the high-speed supernatant of intestinal mucosal homogenates by heat treatment, gel filtration, and ion-exchange chromatography. The physical, spectral, and kinetic properties of the heat-labile protein component strongly suggest that it is xanthine oxidase. By promotion of the oxidation and incorporation of iron into transferrin, intestinal xanthine oxidase could perform a similar function in iron absorption as ceruloplasmin serves in the mobilization of iron from liver stores.
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PMID:Purification and characterization of the intestinal promoter of iron(3+)-transferrin formation. 625 34

Oxygen-derived free radicals have been proposed as general mediators of tissue injury in a variety of disease states. Recent interest has focused on the possibility that free radicals may be involved in ischemic myocardial damage. However, the exact types of damage that result from myocardial exposure to free radicals remains to be established. The purpose of this study was to evaluate the effects of superoxide and hydroxyl radicals on myocardial structure and function in an isolated perfused rabbit interventricular septal preparation. Superoxide was generated by adding purine (2.3 mM) and xanthine oxidase (0.01 U/ml) to the physiological solutions perfusing the septa. Hydroxyl radical generation was catalyzed by the addition of 2.4 microM Fe3+-loaded transferrin to the system. Exposure of normal septa to superoxide-generating solutions resulted in the development of structural alterations in the vascular endothelium including the development of vacuoles. Membranous cellular debris was evident in the extracellular space and within the vessels. Cardiac myocytes showed evidence of mild alterations. Exposure of septa to solutions capable of generating hydroxyl radicals resulted in more extensive and severe damage. Vascular endothelial cells showed evidence of vacuoles or blebs and edema. Severe swelling of mitochondria was evident in cardiac myocytes and vascular endothelial cells. In addition, myocytes often showed blebbing of the basement membrane. Normal septa exposed to superoxide showed no significant decrease in developed tension, whereas hydroxyl radical exposure resulted in a significant decrease in myocardial function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial alterations due to free-radical generation. 633 Nov 79

Previous work has shown that the Pseudomonas-derived protease, pseudomonas elastase (PAE), can modify transferrin to form iron complexes capable of catalyzing the formation of hydroxyl radical (.OH) from neutrophil (PMN)-derived superoxide (.O2-) and hydrogen peroxide (H2O2). As the lung is a major site of Pseudomonas infection, the ability of these iron chelates to augment oxidant-mediated pulmonary artery endothelial cell injury via release of 51Cr from prelabeled cells was examined. Diferrictransferrin previously cleaved with PAE significantly enhanced porcine pulmonary artery endothelial cell monolayer injury from 2.3-6.3 to 15.8-17.0% of maximum, resulting from exposure to H2O2, products of the xanthine/xanthine oxidase reaction, or PMA-stimulated PMNs. Iron associated with transferrin appeared to be responsible for cell injury. Spin trapping and the formation of thiobarbituric acid-reactive 2-deoxyribose oxidation products demonstrated the production of .OH in this system. The addition of catalase, dimethyl thiourea, and the hydrophobic spin trap, alpha-phenyl-n-terbutyl-nitrone, offered significant protection from injury (27.8-58.2%). Since sites of Pseudomonas infection contain other proteases, the ability of porcine pancreatic elastase and trypsin to substitute for PAE was examined. Results were similar to those observed with PAE. We conclude .OH formation resulting from protease alteration of transferrin may serve as a mechanism of tissue injury at sites of bacterial infection and other processes characterized by increased proteolytic activity.
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PMID:Protease-cleaved iron-transferrin augments oxidant-mediated endothelial cell injury via hydroxyl radical formation. 776 95

The effects of a xanthine oxidase-mediated free radical-generating system containing purine and iron-loaded transferrin or solutions containing hydrogen peroxide and iron-loaded transferrin on substrate utilization and high-energy phosphates were evaluated by nuclear magnetic resonance (NMR) spectroscopy in isolated perfused rat hearts. Hearts were supplied with lactate, acetate, and glucose, and the contribution of each substrate to acetyl coenzyme A was measured in control hearts and in the presence of a free radical-generating system. Perfused hearts were monitored by 31P NMR, and tissue extracts were analyzed by 13C NMR. Free radicals decreased the phosphocreatine and beta-ATP peak areas and reduced contractile function. Under control conditions, lactate, acetate, and endogenous sources were the major contributors of acetyl coenzyme A units, with only 5% originating from glucose. In the presence of a xanthine oxidase-mediated free radical-generating system, the glucose contribution increased to 54%, while contributions from acetate and endogenous sources were significantly reduced. Both 13C and 31P NMR analyses showed no significant accumulation of glycolytic sugar phosphates, suggesting little inhibition of glyceraldehyde-3-phosphate dehydrogenase. The increased contribution of glucose to the tricarboxylic acid cycle relative to acetate and endogenous sources is consistent with activation of pyruvate dehydrogenase. In contrast, hearts exposed to a hydrogen peroxide-based free radical-generating system showed an increase in lactate utilization, a decrease in acetate utilization, and no change in glucose utilization compared with control hearts. Glycolytic sugar phosphates were found to accumulate, suggesting possible inhibition of glyceraldehyde-3-phosphate. Thus, different radicals or their metabolites may have varying effects on myocardial metabolism.
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PMID:Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts. 791 69

The generation of free radicals in the progression of kainic acid (KA)-mediated neuronal death has been implicated in both in vitro and in vivo studies. In the present study, the association between KA-induced neurodegeneration and the appearance of lipid peroxidation products was investigated and compared to three well characterized free radical generating (FRG) systems: 200 microM ferrous ammonium sulfate (FAS), 20 microM copper (Cu2+), and 0.01 U/ml xanthine oxidase/2.3 mM purine/2.4 microM transferrin (XO). KA caused a dose-dependent increase in conjugated diene and lipid hydroperoxide formation as did the FRG systems. The antioxidant, butylated hydroxytoluene (BHT), decreased both FRG system- and KA-induced lipid peroxidation by approximately 60-70%. Unlike BHT, the potency of the lipid peroxidation inhibitor, U78517F, depended upon the system utilized to induce free radical generation. U78517F was most potent in attenuating FAS-induced lipid peroxidation (100 nM), followed by KA (1.5 microM), and then Cu2+ and XO (> 2 microM). Results were confirmed by measurement of cytolysis through the release of lactic dehydrogenase (LDH). These data provide further evidence that the generation of free radicals, subsequently leading to membrane disruption, is central to the mechanism of KA-elicited neuronal death in cultures of cerebellar granule cells.
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PMID:Kainic acid-induced lipid peroxidation: protection with butylated hydroxytoluene and U78517F in primary cultures of cerebellar granule cells. 825 95

Catalysis of the formation of reactive oxygen species (RO2S) by low molecular weight complexes of iron has been implicated in several pathological conditions in the retina since photoreceptors and retinal pigment epithelial cells are likely to be especially sensitive to RO2S. Since protective proteins cannot cross the blood-retinal barrier, it is likely that the retina performs its own protective functions by synthesizing proteins that bind iron and nonprotein iron complexes, the major catalysts of RO2S generation. Investigations were carried out to determine whether pigment epithelial cells are themselves sensitive to iron-generated RO2S and whether apo-transferrin and apo-hemopexin, known to be made locally in the retina, can perform a protective function. In 51Cr release assays, the toxicity of exogenous RO2S including hydrogen peroxide or superoxide (generated by xanthine oxidase/hypoxanthine) to human retinal pigment epithelial cells was inhibited by the iron chelators, desferrioxamine and apo-transferrin. Free but not protein-bound ferric iron and heme exacerbated the toxic effect. The toxic effect of heme was abolished by the heme-scavenging, extracellular antioxidant, apo-hemopexin, and also by exogenous bovine serum albumin. In addition, heme toxicity was inhibited by a 3 h preincubation of cells with either heme, apo-hemopexin, or heme-hemopexin 24 h prior to the toxicity assay. It is concluded, first, that toxic effects of iron and heme can be prevented by apo-transferrin or apo-hemopexin and, second, that exposure of RPE cells to free heme or hemopexin sets in motion a series of biochemical events resulting in protection against oxidative stress. It is probable that these include heme oxygenase induction.
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PMID:Heme-mediated reactive oxygen species toxicity to retinal pigment epithelial cells is reduced by hemopexin. 864 26

The involvement of "free" iron in damage caused by oxidative stress is well recognized. Superoxide generated in a short burst and at a relatively high flux by the xanthine/xanthine oxidase couple is known to release iron from ferritin in the presence of phenanthroline derivatives as iron chelators. However, superoxide generation via xanthine oxidase is accompanied by the simultaneous direct generation of hydrogen peroxide and, in the presence of ferritin, there is also a superoxide-independent release of iron. In this study it was found that the iron chelator employed attenuates superoxide formation from the xanthine/xanthine oxidase couple. The reaction of ferritin and transferrin with a clean chemical source of superoxide, di(4-carboxybenzyl)hyponitrite (SOTS-1) was therefore investigated. The efficiency of superoxide-induced iron release from ferritin increases dramatically as the superoxide flux is decreased, reaching as high as 0.5 Fe per O2*-. Treatment of ferritin for 16 h with SOTS-1 yielded as many as 130 Fe atoms/ferritin molecule, which greatly exceeds the amount of possible "contaminating" iron absorbed on the protein shell.
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PMID:Effect of a prolonged superoxide flux on transferrin and ferritin. 1106 77


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