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

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high-speed supernatant from homogenates of rat small intestine contains a heat-stable, dialyzable factor which showed a time-dependent inhibition of peroxidase activity in salt extracts of the tissue. The inhibitor was purified by chromatography on Dowex 50W-X8 and identified as xanthine. The inhibition of peroxidase by xanthine was prevented by allopurinol, an inhibitor of xanthine oxidase, and hypoxanthine was also found to be inhibitory. H2O2, produced in the reaction catalyzed by xanthine oxidase, was shown to be directly responsible for the observed inhibition. The time-dependent loss of peroxidase activity in the presence of xanthine or hypoxanthine occurred more rapidly in NH4Cl than in CaCl2 extracts of small intestine and was due to the difference in the initial concentration of H2O2 in these two extracts. The possible relationship between peroxidase and xanthine oxidase in the rat small intestine is discussed.
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PMID:Rat intestinal peroxidase: inhibition by endogenous xanthine and xanthine oxidase. 383 43

For the three Gram-negative bacteria, Pseudomonas fluorescens, Escherichia coli, and Erwinia amylovora, p-benzoquinone was the principal bactericidal agent formed in vitro during the oxidation of hydroquinone by horseradish peroxidase, whereas no toxicity could be associated with either phenolic or oxygen-free radicals. Even the continuous generation of p-benzosemiquinone during the simultaneous reduction of p-benzoquinone by xanthine oxidase and reoxidation of hydroquinone by peroxidase was no more toxic than p-benzoquinone alone. Anaerobiosis had no effect on the toxicity of either p-benzoquinone or the peroxidase reaction and the generation of superoxide and hydroxyl radicals catalyzed by xanthine oxidase was not bactericidal. Substitutions on the p-benzoquinone ring decreased quinone toxicity in rough proportion to the decrease in quinone redox potential, suggesting that strong oxidizing potentials are important for such quinone toxicity.
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PMID:Bactericidal agents generated by the peroxidase-catalyzed oxidation of para-hydroquinones. 393 58

Previous studies indicate that vascular permeability is increased in skeletal muscle subjected to 4 hours of inflow occlusion. However, the mechanism(s) underlying the increase in permeability are unknown. The aim of this study was to assess the role of oxygen-derived free radicals and histamine as putative mediators of the increased permeability in skeletal muscle subjected to 4 hours of inflow occlusion. The osmotic reflection coefficient for total plasma proteins and isogravimetric capillary pressure were estimated in canine gracilis muscle for the following conditions: control, ischemia, and ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), catalase (a peroxidase that reduces hydrogen peroxide to water and molecular oxygen), superoxide dismutase (a superoxide anion scavenger), dimethyl sulfoxide (a hydroxyl radical scavenger), diphenhydramine (a histamine H1-receptor blocker), or cimetidine (a histamine H2-receptor blocker). Ischemia, followed by reperfusion, significantly reduced the reflection coefficient from 0.94 +/- 0.02 to 0.64 +/- 0.02 and isogravimetric capillary pressure from 13.8 +/- 1.0 mm Hg to 6.9 +/- 0.4 mmHg, indicating a dramatic increase in microvascular permeability. Prior treatment with diphenhydramine or cimetidine did not significantly alter the permeability increase induced by ischemia. However, pretreatment with allopurinol, catalase, superoxide dismutase, or dimethylsulfoxide did significantly attenuate the increase in vascular permeability. The results of this study indicate that oxygen radicals are primarily responsible for the increased vascular permeability produced by ischemia-reperfusion, that the hydroxyl radical may represent the primary damaging radical, and that xanthine oxidase may represent the primary source of oxygen-derived free radicals in ischemic skeletal muscle.
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PMID:The role of oxygen-derived free radicals in ischemia-induced increases in canine skeletal muscle vascular permeability. 404 85

The origin of luminol-dependent chemiluminescence (CL) in neutrophils stimulated by immune complexes (IC) was investigated. It was found that CL induced by soluble IC and aggregated human gamma globulin (AHG) was glucose-independent, while insoluble IC-induced CL was diminished in the absence of glucose. AHG-induced CL was not inhibited by superoxide dismutase, catalase or 2,5-dimethyl furan, but was suppressed in the presence of phenol, sodium benzoate, sodium formate and mannitol. The CL was also inhibited by inhibitors of arachidonic acid (AA) metabolism including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin and aspirin, and by prostaglandins E1 and E2, theophylline and dibutyryl cyclic AMP. Luminol-dependent CL was also studied in cell-free systems including AA plus soybean lipoxygenase, hydroperoxyeicosatetraenoic acid plus peroxidase and xanthine oxidase plus xanthine. Our results indicate that, in neutrophils exposed to soluble IC and AHG, CL is produced and this is closely linked to the formation of free radicals during the metabolism of AA. The radical(s) involved is likely to include the hydroxyl radical. In neutrophils stimulated by large aggregates of IC or micro-organisms, superoxide anion, H2O2 and singlet oxygen are also produced as a result of activation of NAD(P)H oxidase. These oxygen species function as oxidizing agents for AA metabolism and amplify the production of hydroxyl radical along the lipoxygenase (and possibly cyclooxygenase) pathway(s).
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PMID:Luminol-dependent chemiluminescence produced by neutrophils stimulated by immune complexes. 608 70

Neutrophil-mediated injury to lung parenchymal cells has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. As an in vitro model of neutrophil-mediated injury, this study used activated human neutrophils as effector cells in an 18-h cytotoxicity assay with 51Cr-labeled bovine pulmonary artery endothelial cells serving as target cells. Neutrophils effectively injured pulmonary endothelial cells, expressed as cytotoxic index (CI), of 63.8 +/- 5.4, and this injury could be significantly reduced by several agents, including 1% dimethyl sulfoxide (CI, 51.3 +/- 3.7), 50 micrograms/ml ascorbic acid (CI, 40.8 +/- 4.7), and especially 1,100 U/ml catalase (CI, 14.3 +/- 4.1). As cell-free models of neutrophil-mediated endothelial cell injury, H2O2 (30 microM), O2- (generated by 0.5 mU xanthine oxidase), and the myeloperoxidase-dependent (0.32 U) hypohalite ion were each capable of injuring the target cells with CI of 6.21 +/- 2.8, 53.6 +/- 5.3, and 21.2 +/- 1.5, respectively. Catalase was effective in reducing the injurious effect of each of these oxidant-generating systems (p less than 0.01, all comparisons), confirming the important role for H2O2 in the mediation of this injury. The data indicate that neutrophils are capable of killing pulmonary endothelial cells by a pathway largely dependent on the generation of H2O2, and suggest the possibility that removal of H2O2 from the alveolar structures in subjects with these disorder might be an effective future therapeutic approach.
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PMID:Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury. 608 99

The antibody-dependent cell-mediated cytoxicity (ADCC) by human monocytes and neutrophils was investigated by measuring the release of 51chromate from prelabeled erythrocytes coated with immunoglobulin G. ADCC was found to be positively correlated to phagocytosis of 51Cr-labeled erythrocytes and to the postphagocytic events of the effector cells, activation of the hexose monophosphate shunt, and degranulation. Exclusion of oxygen from the incubation media halved the ADCC by both cell types without affectijg phagocytosis or degranulation. Likewise, ADCC by cells from patients suffering from chronic granulomatous disease (CGD) was only half the intensity of ADCC by cells from normals. Inhibitors of mitochondrial respiration were without depressing effect of ADCC. Azide, which in addition to its blocking action on oxydative phosphorylation also inhibits catalase and myeloperoxidase, resulted in a approximately equal to 40% stimulation of ADCC by cells from normals but was without effect of ADCC by cells from CGD patients. The hydroxyl radical scavenger, mannitol, significantly depressed ADCC by cells from normals (P < 0.01) but was without effect on cells from CGD patients. Azide and mannitol also were without effect on ADCC by normal cells when oxygen was excluded. In a xanthine-xanthine oxidase system, erythrocytes were effectively lysed. This lysis was inhibited by catalase, superoxide dismutase, and mannitol. When comparable concentrations of glucose oxidase were used no lysis was observed. H2O2 either alone or in combination with azide did not lyse erythrocytes. It is suggested that ADCC by both monocytes and neutrophils is partly dependent on the generation of hydroxyl radicals by the effector cells.
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PMID:Role of oxygen in antibody-dependent cytotoxicity mediated by monocytes and neutrophils. 625 48

In previous studies, we noted that Candida hyphae and pseudohyphae could be damaged and probably killed by neutrophils, primarily by oxygen-dependent nonphagocytic mechanisms. In extending these studies, amount of damage to hyphae again was measured by inhibition of [(14)C]cytosine uptake. Neutrophils from only one of four patients with chronic granulomatous disease damaged hyphae at all, and neutrophils from this single patient damaged hyphae far less efficiently than simultaneously tested neutrophils from normal control subjects. Neutrophils from neither of two subjects with hereditary myeloperoxidase deficiency damaged the hyphae. This confirmed the importance of oxidative mechanisms in general and myeloperoxidase-mediated systems in particular in damaging Candida hyphae. Several potentially fungicidal oxidative intermediates are produced by metabolic pathways of normal neutrophils, but their relative toxicity for Candida hyphae was previously unknown. To help determine this, cell-free in vitro systems were used to generate these potentially microbicidal products. Myeloperoxidase with hydrogen peroxide, iodide, and chloride resulted in 91.2% damage to hyphal inocula in 11 experiments. There was less damage when either chloride or iodide was omitted, and no damage when myeloperoxidase was omitted or inactivated by heating. Azide, cyanide, and catalase (but not heated catalase) inhibited the damage. Systems for generation of hydrogen peroxide could replace reagent hydrogen peroxide in the myeloperoxidase system. These included glucose oxidase, in the presence of glucose, and xanthine oxidase, in the presence of either hypoxanthine or acetaldehyde. In the presence of myeloperoxidase and a halide, the toxicity of the xanthine oxidase system was not inhibited by superoxide dismutase and, under some conditions, was marginally increased by this enzyme. This suggested that superoxide radical did not damage hyphae directly but served primarily as an intermediate in the production of hydrogen peroxide. The possible damage to hyphae by singlet oxygen was examined using photoactivation of rose bengal. This dye damaged hyphae in the presence of light and oxygen. The effect was almost completely inhibited by putative quenchers of singlet oxygen: histidine, tryptophan, and 1,4-diazobicyclo[2.2.2]octane. These agents also inhibited damage to hyphae by myeloperoxidase, halide, and either hydrogen peroxide or a peroxide source (xanthine oxidase plus acetaldehyde). Myeloperoxidase-mediated damage to hyphae was also inhibited by dimethyl sulfoxide, an antioxidant and scavenger of the hydroxyl radical. These data support the involvement of oxidative mechanisms and the myeloperoxidase-H(2)O(2)-halide system, in particular in damaging hyphae in vitro and perhaps in vivo as well.
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PMID:Damage to Candida albicans hyphae and pseudohyphae by the myeloperoxidase system and oxidative products of neutrophil metabolism in vitro. 625 27

The effects of the beta-receptor blockading agents, metoprolol and sotalol on neutrophil random motility, chemotaxis, post-phagocytic glycolysis, superoxide production, hexose monophosphate shunt activity, myeloperoxidase (MPO) mediated protein iodination and hydrogen peroxide production were assessed in vitro. The concentration range investigated was 10(-8)--10(-2) M for each drug. Both agents caused significant stimulation of neutrophil motility at concentrations of more than 10(-4) M. Increased migration was not associated with increased glycolysis or significant cyclic nucleotide fluctuations, but was inversely related to inhibition of superoxide and hydrogen peroxide generation and MPO mediated iodination with both drugs. In a further series of experiments to determine the relationship between the drug induced inhibition of H2O2 production and MPO mediated protein iodination to stimulation of motility it was found that concentrations of sotalol and metoprolol that caused these effects prevented HRP/H2O2/I- induced inactivation of the leucoattractant and inhibition of neutrophil chemotactic responsiveness. Neither drug inhibited the activity of MPO per se nor the reduction of ferricytochrome c by superoxide generated by the xanthine: xanthine oxidase system in vitro. It is suggested that enhanced neutrophil motility is not related to beta-receptor blockade but rather to restricting the availability of hydrogen peroxide and reactive products of the MPO/H2O2/halide system.
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PMID:In vitro stimulation of neutrophil motility by metoprolol and sotalol related to inhibition of both H2O2 production and peroxidase mediated iodination of the cell and leucoattractant. 625 68

The distal articular surface of the femur was surgically removed in 57 dogs. Succinate dehydrogenase and cytochrome oxidase activities were assayed on postoperative days 7, 20, 26, 33 and 70 in the regenerating, chondrifying articular surface and in the granulation tissue adhering to the capsule. In the 70-day samples, the cyanide-induced inhibition of oxygen consumption was determined and enzyme histochemical reactions (cytochrome oxidase, monoamine oxidase, xanthine oxidase, peroxidase and "catalase") were performed. The succinate dehydrogenase activity was the highest in the early postoperative stage in both tissues. This was followed by a definite decrease and a subsequent significant increase in activity when chondrification took place. Measurement of cytochrome oxidase activity could not reveal any convincing result, presumably because of the properties of the tissues studied. The oxygen consumption by the chondrifying articular surface at 70 days was inhibited to about 50% by cyanide, and about 90% inhibition was observed in the tissue adhering to the capsule. The cells of the regenerating articular surface possess cytochrome oxidase and a cyanide- (and sodium azide-) resistant oxidase activity. The enzyme activity of the cartilaginous islets exceeded that of their connective tissue environment. The cytochrome oxidase activity increased in the cells during cartilage differentiation. Presumably, some further cyanide-sensitive and cyanide-resistant oxidases are present in chondroblasts and young chondrocytes.
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PMID:Studies on cartilage formation. XXII. Investigations of certain oxidative metabolic processes in regenerating articular cartilage. 626 95

The effects of dapsone on polymorphonuclear leukocyte functions and lymphocyte mitogen-induced transformation were assessed in vitro and in vivo in normal individuals and in newly diagnosed untreated patients with lepromatous leprosy. The effects of dapsone on the cell-free generation of superoxide by the xanthine: xanthine oxidase system and iodination of bovine serum albumin by horseradish peroxidase were also investigated. In normal individuals dapsone mediated stimulation of polymorphonuclear leukocyte migration in vitro and vivo. Dapsone had no effect on postphagocytic hexose monophosphate shunt activity in vivo. Similar effects were found in patients with lepromatous leprosy. Dapsone also decreased the inhibitory activity of serum from patients with lepromatous leprosy on normal polymorphonuclear leukocyte migration in vitro. Progressive loss of serum-mediated inhibition of migration was observed after ingestion of dapsone by the patients. Further experiments showed that stimulation of polymorphonuclear leukocyte motility was related to inhibition of lymphocyte transformation at high concentrations in vitro, but had slight stimulatory activity on phytohemagglutinin-induced transformation in controls and patients in vivo.
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PMID:In vitro and in vivo effects of dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy. 626 48


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