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)

Group B streptococci (GBS) lack catalase, and they produce and release H2O2;thus, they should be readily killed by phagocytes with a diminished respiratory burst. Surprisingly, although strains of Staphylococcus aureus were killed at H2O2 concentrations greater than 0.5 mM, GBS strains were killed only at concentrations greater than 5mM. In contrast, GBS were killed by hydroxyl radicals generated by the xanthine oxidase-acetaldehyde system at O2 fluxes greater than or equal to 3.5 nmol/ml per min, whereas O2 fluxes greater than or equal to 10 nmol/ml per min were required to kill the S. aureus strains. Results with virulent and laboratory strains of GBS were similar. The differences in susceptibility of GBS and S. aureus seemed to correlate with differences in content of endogenous oxygen-metabolite scavengers. GBS contained approximately 100-fold more glutathione and approximately 20-fold more glutathione reductase than did S. aureus, whereas S. aureus was rich in catalase that GBS lacked. GBS that were grown in buthionine sulfoximine, however, contained 87% less glutathione than did controls but were not more susceptible to killing by H2O2 or the xanthine oxidase-acetaldehyde system. Similarly, the relative susceptibility of GBS to tert-butyl hydroperoxide and H2O2 paralleled that of S. aureus. Thus, inherent differences in susceptibility of vital cellular functions to oxidative damage rather than content of oxygen-metabolite scavengers may account for the differences in susceptibility of GBS and S. aureus.
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PMID:Comparative susceptibility of group B streptococci and Staphylococcus aureus to killing by oxygen metabolites. 299 35

Xanthine (X) and xanthine oxidase (XO) were injected intratracheally (IT) in hamsters at Day 0 (38 mg X, 100 micrograms XO) and Day 5 (38 mg X, 250 micrograms XO). Control hamsters received saline or X (38 mg) plus boiled XO (100, 250 micrograms). Cytoplasmic superoxide dismutase (SOD) activity increased from control of 286 to 337 and 335 units/lung at Days 12 and 19, respectively, but decreased to 228 units/lung at Day 33; mitochondrial SOD activity increased at Day 12 from control of 57 to 71 units/lung and then decreased at Days 26 and 33 to 42 and 33 units/lung, respectively. Glutathione peroxidase (GP) and glutathione reductase (GR) activities rose from their control values of 1161 and 1151 to 1561 and 2287 units/lung at Day 12, respectively; thereafter, GR activity decreased to 512 and 462 units/lung at Days 19 and 26, respectively. Glutathione transferase declined at Day 12 but increased at Day 26 after initial treatment. Glucose-6-phosphate dehydrogenase activity declined from control of 1071 to 693 units/lung at Day 2 and returned to control thereafter. Catalase activity remained unaffected. Hydroxyproline was increased from 903 micrograms/lung in control to 1080, 1301, 1195, and 1148 micrograms/lung at Days 12, 19, 26, and 33, respectively. Malonaldehyde increased from 40 nmole/lung in control to 70 and 113 nmole/lung at Days 12 and 33, respectively. The ratio of right ventricle to left ventricle and septum increased significantly from control of 0.277 to 0.318 at Day 33. Histopathology at Days 2 and 4 revealed peribronchiolar and arteriolar inflammation, and diffuse alveolitis. By Day 12 there were thickened alveolar septa and foci of fibrotic consolidation.
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PMID:Effects of intratracheal administration of xanthine plus xanthine oxidase on lung antioxidant enzymes, lipid peroxidation, and collagen in hamsters. 319 17

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 mechanism of the enhancing effect of methyl viologen (MV) and flavin-adenine dinucleotide (FAD) on sulfoxide reduction which is mediated by a combination of aldehyde oxidase (AO) from guinea pig liver and one-electron reducing flavoenzymes, such as milk xanthine oxidase (XO), was examined. The activity of anaerobic reduction of diphenyl sulfoxide (DPSO) to diphenyl sulfide (DPS) was less than 1 nmol/min/mg protein of AO preparation in a system consisting of hypoxanthine, XO and AO. However, the sulfoxide reduction by this system was enhanced about 6- and 100-fold by the additions of FAD and MV, respectively. In the system containing MV or FAD, other one-electron reducing flavoenzymes such as nicotinamide adenine dinucleotide (reduced form) (NADH) dehydrogenase, lipoamide dehydrogenase and glutathione reductase with an appropriate electron donor, could replace XO. The ability of supplemented flavoenzymes to facilitate DPSO reduction correlated with their abilities to reduce MV and FAD. When AO was omitted from the combined system, no sulfoxide reduction was observed. Stoichiometric study revealed that MV semiquinone and FADH2 were oxidized at ratios of 2 and 1 mol, respectively, per mol of DPS formed. These results indicate that either MV or FAD serves as an electron carrier from the supplemented flavoenzymes to AO, a terminal reductase of sulfoxide.
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PMID:Sulfoxide reduction catalyzed by guinea pig liver aldehyde oxidase in combination with one-electron reducing flavoenzymes. 383 63

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 effect of tris-(2-chloroethyl)-amine (HN-3) on RNA and DNA was investigated spectrophotometrically. The shift in the absorbance spectrum caused by the addition of HN-3 was used to test a variety of compounds for their ability to inhibit RNA alkylation. The effect of HN-3 on the activity of several enzymes was also investigated. The activities of ribonuclease A, desoxyribonuclease I, acetylcholinesterase, diaphorase, glutathione reductase, adenosine desaminase, glyoxalase I, 3-hydroxyacyl-CoA-dehydrogenase, xanthine oxidase, glucose-6-phosphate dehydrogenase, hexokinase and the microsomal N-oxygenation of aniline were not changed by HN-3, whereas the activity of cytochrome-c-reductase exhibited a dose dependent diminution in the presence HN-3. Of 105 compounds tested only 14, namely, sodium thiosulfate, dithioxanthine, thiosalicylic acid, 1,2,4-triazole-5-thiol, 2-thiocytosine, 2-thiohistadine, 2,3-dithiosuccinic acid, thioglycolic acid, 3-mercapto-D-valine,6-amino-2-thiouracil, thionicotine amide, dithiothreitol, sodium sulfite, and ergothioneine prevented the alkylation of RNA. All of them also reacted with HN-3 in absence of RNA. No correlation was found between the reaction constant of the reaction compound:HN-3 in the absence of RNA and the concentration of the compound which inhibited RNA alkylation by 50%. The compounds which were effective in vitro were also tested in mice for their ability to reduce HN-3 toxicity in vivo. Only sodium thiosulfate, d-penicillamine, and dithiosuccinic acid were effective. A 3.9fold increase in the LD50 of HN-3 was achieved in mice treated with sodium thiosulfate 3330 mg/kg i.p., a 1.7fold with 2125 mg dithiosuccinic acid/kg, and a 2fold increase with 2500 mg/kg d-penicillamine. The compound tested was injected i.p. 0.5 to 1 min after the s.c. injection of HN-3.
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PMID:Effect of various compounds on the reaction of tris-(2-chloroethyl)amine with ribonucleic acid in vitro and on its toxicity in mice. 617 33

Erythrocytes from young and old rats were separated into four age fractions by density-gradient centrifugation. The specific activities per cell were determined for glucose-6-phosphate dehydrogenase (EC 1.1.1.49), glutathione peroxidase (EC 1.11.1.9), glutathione reductase (EC 1.6.4.2) and catalase (EC 1.11.1.6). Decreased specific activities were observed with increasing cell age for all four enzymes in both young and old animals. In addition, significant differences in the activities of these enzymes were observed between cells of the same age fraction from young and old donors. Susceptibility of fractionated erythrocytes to oxidative attack in vitro generated by incubation with xanthine/xanthine oxidase increased with both cell and animal age. The amount of membrane-lipid peroxidation also increased with cell and animal aging, as measured by both thiobarbituric acid and fluorescent chromolipid assays. Increases of 2-3-fold in the contents of lipid peroxides were observed between the youngest and oldest age fractions of young rats. Lipid peroxide contents in young cells of old animals were equal to those in old erythrocytes from young rats and increased by 30% with cell aging in the old donors. These results suggest that the extent of enzymic protection against oxidative and peroxidative damage decreases with erythrocyte aging. More importantly, enzymic protection in cells of old rats is considerably decreased already in the early stages of their lifespan.
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PMID:Decreased enzymic protection and increased sensitivity to oxidative damage in erythrocytes as a function of cell and donor aging. 671 29

Regulation of induced nitric oxide synthase in rat hepatocyte primary cultures was explored. Nitric oxide synthase (NOS) induction by tumor necrosis factor-alpha (TNF alpha) is synergized by interferon-gamma, and both NOS activity and gene expression are maximal by 10 h and maintained through 24 h. Glutathione depletion by diethylmaleate, which conjugates reduced glutathione, 1,3-bis(chloroethyl)-1-nitrosourea (BCNU), a glutathione reductase inhibitor, or buthionine sulfoxamine, a glutathione synthesis inhibitor, abolishes or reduces NOS induction in TNF alpha-treated hepatocytes, whereas N-acetylcysteine has little effect. Thus, reduced glutathione is critical to NOS mRNA induction and activity in TNF alpha-treated hepatocytes. NOS induction in TNF alpha-treated cells is reduced by rotenone, a mitochondrial complex 1 inhibitor. Concurrent treatment with TNF alpha and the antioxidant, Trolox, or the iron-chelating agent, desferrioxamine, also reduces NOS activity. Dithiothreitol, a thiol antioxidant, reduced TNF alpha induction of NOS. Trolox and BCNU, combined, blocked TNF alpha stimulation of NOS greater than either agent alone. These results suggest that TNF alpha increases mitochondrial production of reactive oxygen intermediates (ROI), which contributes to NOS induction. Hepatocytes exposed to extracellular ROI generation through a xanthine/xanthine oxidase superoxide-generating system expressed increased NOS activity and mRNA levels. NOS induction by superoxide also requires reduced glutathione since diethylmaleate blocks induction by xanthine/xanthine oxidase while N-acetylcysteine elevates NOS expression. Thus, the generation of ROI by cytokines or other physiological processes stimulates the induction of NOS and this process is regulated by cellular levels of reduced glutathione.
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PMID:Regulation of hepatic nitric oxide synthase by reactive oxygen intermediates and glutathione. 753 84

In the present study we have examined the potential role of xanthine oxidase (XO) in the intracellular oxidative stress induced by combinations of recombinant murine TNF alpha (rMuTNF alpha) and murine interferon-gamma (IFN gamma) in cultured mouse hepatocytes. IFN gamma alone and the combination of rMuTNF alpha and IFN gamma increased XO activity after a 4 hr exposure period. rMuTNF alpha alone increased XO activity only after 24 hr. At the later time point, the increased XO activity was accounted for by decreased XDH activity. However, the apparent conversion of XDH to XO cannot account for the early effects of rMuTNF alpha on hepatocyte function, particularly the onset of an oxidative stress (as indicated by efflux of GSSG from the hepatocytes). This effect is observed after two hours, and it is temporally the earliest sign of alteration of cellular function caused by rMuTNF alpha. Increased XO activity was not observed until 4 hr after treatment with rMuTNF alpha/IFN gamma. In addition, inhibition of XO activity with allopurinol did not ameliorate GSSG efflux from hepatocytes treated with the cytokines. However, the ATP depletion caused by the combination of rMuTNF alpha and IFN gamma and the cytotoxicity observed with the combined cytokines in cells pre-treated with BCNU (to inhibit glutathione reductase) was inhibited by allopurinol. These results show that the onset of oxidative stress in cultured mouse hepatocytes is not due to conversion of XDH to XO. However, events which follow the efflux of GSSG, such as ATP depletion and cytotoxicity in cells with impaired anti-oxidant defenses, may be partially due to increased XO activity, especially in cells treated with both rMuTNF alpha and IFN tau.
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PMID:The role of xanthine oxidase in oxidative damage caused by cytokines in cultured mouse hepatocytes. 796 49

The authors investigated the mechanisms caused by oxidants (superoxide and hydrogen peroxide) and asbestos (amosite) fibers in human mesothelial cells. Immortalized human pleural mesothelial cells (MET 5A) were exposed in vitro to one of the following: hypoxanthine (100-200 microM) plus xanthine oxidase (10-20 mU/ml) as a superoxide-generating system, H2O2 (50 microM-5 mM); or amosite (1-100 micrograms/cm2). Cellular adenine nucleotide depletion, DNA single strand breaks, extracellular release of nucleotides, and their catabolites and lactate dehydrogenase (LDH) were assessed as markers of cell damage after 4-6 h exposure to the oxidants or fibers. The effect of intracellular antioxidant enzymes and exogenous antioxidants on cell damage were investigated during oxidant and amosite exposure. Superoxide radical and H2O2 exposure resulted in the depletion of adenine nucleotides, accumulation of the products of nucleotide catabolism, induction of DNA single strand breaks, and extracellular LDH release. Amosite exposure did not cause nucleotide depletion or induction of DNA single strand breaks. Inactivation of the intracellular antioxidant enzymes glutathione reductase or catalase augmented cell damage during H2O2 exposure but not during amosite exposure.
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PMID:Cytotoxicity of oxidants and asbestos fibers in cultured human mesothelial cells. 800 12


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