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 ability of various reactive oxygen species and serine proteases to activate latent collagenase (matrix metalloproteinase-1) purified from human neutrophils was examined. Latent 70-75 kD human neutrophil collagenase (HNC) was efficiently activated by known non-proteolytic activators phenylmercuric chloride (an organomercurial compound) and gold thioglucose (Au(I)-salt). Corresponding degree of activation was achieved by reactive oxygen species including hypochlorous acid (HOCl), hydrogen peroxide (H2O2) and hydroxyl radical generated by hypoxanthine/xanthine oxidase (HX/XAO). The presence of trace amounts of iron and EDTA were necessary and even enhanced H2O2 induced activation of latent HNC. This activation could be abolished by an iron chelator desferrioxamine and a hydroxyl radical scavenger mannitol. HOCl induced activation of latent HNC was not affected by desferrioxamine and mannitol. Thus, these compounds do not inhibit the active/activated form of HNC. Latent HNC could also be activated by trypsin and chymotrypsin but not by plasmin and plasma kallikrein. The ability of mannitol and desferrioxamine to inhibit the H2O2-induced activation of HNC suggests the transition metal dependent Fenton reaction to be responsible for localized and/or site-specific generation of hydroxyl radical/hydroxyl radical -like oxidants to act as the activating oxygen species. Our results support the ability of myeloperoxidase derived HOCl to act as a direct oxidative activator of HNC and further suggest the existence of a new/alternative oxidative activation pathway of HNC involving hydroxyl radical.
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PMID:Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteases. 217 13

H2O2-mediated cytotoxicity (as measured by 51Cr-release) of rat pulmonary artery endothelial cells was time-dependent and related to the concentration of H2O2 employed. The cytotoxic effects of H2O2 were, as expected, prevented by catalase and the degree of protection was directly related to its time of addition. Endothelial cells were incubated with [14C]adenosine to achieve intracellular labeling of ATP, after which the cells were exposed to H2O2. Based on analysis of cell extracts by high-performance liquid chromatography, there was a time-dependent loss of intracellular radioactivity and ATP with the simultaneous appearance of purine degradation products including xanthine/hypoxanthine. Approximately 50% of the intracellular ATP was lost after 15 minutes of exposure and up to 80% was lost by 30 minutes. The extracellular fluid of cells exposed to H2O2 contained significant amounts of xanthine/hypoxanthine. The ferric iron chelator deferoxamine provided almost complete protection against H2O2-mediated cytotoxicity. Two inhibitors of xanthine oxidase, allopurinol and oxypurinol, were also protective as was deoxycoformycin, an inhibitor of adenosine deaminase. Remarkably, cells protected by these agents showed the same loss of intracellular ATP as unprotected, H2O2-treated cells. These findings demonstrate the dissociation between ATP loss per se and oxidant injury of endothelial cells. ATP breakdown may be an important event leading to cellular injury in that this results in the formation of substrate for xanthine oxidase.
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PMID:H2O2-mediated cytotoxicity of rat pulmonary endothelial cells. Changes in adenosine triphosphate and purine products and effects of protective interventions. 217 53

Reductive release of iron from ferritin may catalyze cytotoxic radical reactions like the Haber-Weiss reaction. The ability of .O2- to mobilize Fe(II) from ferritin was studied by using the xanthine/xanthine oxidase reaction, with and without superoxide dismutase, and with bathophenanthroline sulphonate as the chelator. Not more than one or two Fe(II)/ferritin molecules could be released by an .O2(-)-dependent mechanism, even after repeated exposures of ferritin to bursts of .O2-. The amount of releaseable iron depended on the size and the age of the iron core, but not on the iron content of the protein shell of ferritin which was manipulated by chelators and addition of FeCl3. The kinetic characteristics of the .O2(-)-mediated iron release indicated the presence of a small pool of readily available iron at the surface of the core. The very limited .O2(-)-dependent release of iron from ferritin is compatible with a protective role of ferritin against toxic iron-catalyzed reactions.
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PMID:On the limited ability of superoxide to release iron from ferritin. 217 70

The susceptibility of rat mast-cell heparin to oxidative degradation was examined. Heparin as a component of intact mast-cell granules (MCG) was degraded following ingestion by normal human neutrophils. In contrast, neutrophils from patients with chronic granulomatous disease (CGD), which do not respond to stimulation with respiratory-burst activity, exhibited a greatly diminished ability to degrade phagocytosed MCG heparin. MCG-associated heparin also was cleaved by H2O2 plus Fe2+ (Fenton's reagent). Isolated heparin proteoglycan (average Mr approx. 750,000) was rapidly cleaved to smaller molecules similar in size to commercial pig heparin upon exposure to Fenton's reagent. This cleavage was inhibited by catalase and by the hydroxyl-radical (OH.)-scavenger mannitol, but not by superoxide dismutase (SOD). The cleavage products retained approx. 26% of the anticoagulant activity of the native molecule. The heparin proteoglycan was also cleaved by acetaldehyde/xanthine oxidase/FeSO4, a system that generates superoxide (O2.-), H2O2 and OH.. Whereas the cleavage at relatively high iron ion concentrations was inhibited by catalase and mannitol but not by SOD, at lower iron ion concentrations the cleavage was inhibited by catalase, mannitol and SOD. These findings suggest the involvement of OH., which at high Fe2+ concentrations is generated by Fenton's reagent (H2O2 plus Fe2+), and at low iron ion concentrations is generated by the iron-ion-catalysed interaction between O2.- and H2O2 (Haber-Weiss reaction). These studies suggest that oxygen radicals generated by activated phagocytes may contribute to the degradation in vivo of both solubilized and granule-associated proteoglycan heparin.
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PMID:Oxidative degradation of rat mast-cell heparin proteoglycan. 217 84

To investigate renal tubular epithelial cell injury mediated by reactive oxygen molecules and to explore the relative susceptibility of epithelial cells and endothelial cells to oxidant injury, we determined cell injury in human umbilical vein endothelial cells and in four renal tubular epithelial cell lines including LLC-PK1, MDCK, OK and normal human kidney cortical epithelial cells (NHK-C). Cells were exposed to reactive oxygen molecules including superoxide anion, hydrogen peroxide and hydroxyl radical generated by xanthine oxidase and hypoxanthine. We determined early sublethal injury with efflux of 3H-adenine metabolites and a decline in ATP levels, while late lytic injury and cell detachment were determined by release of 51chromium. When the cells were exposed to 25, 50, and 100 mU/ml xanthine oxidase with 5.0 mM hypoxanthine, ATP levels were significantly lower (P less than 0.001) in LLC-PK1, NHK-C and OK cells compared to MDCK cells while ATP levels were significantly lower (P less than 0.01) in endothelial cells compared to all tubular cell lines. A similar pattern of injury was seen with efflux of 3H-adenine metabolites. When the cells were exposed to 50 mU/ml xanthine oxidase with 5.0 mM hypoxanthine for five hours, total 51chromium release was significantly (P less than 0.001) greater in LLC-PK1, NHK-C and OK cells compared to MDCK cells, while total 51chromium release was significantly (P less than 0.001) greater in endothelial cells compared to all tubular cells. However, lytic injury was the greatest in LLC-PK1 cells and NHK-C cells while cell detachment was the greatest in endothelial cells. MDCK cells were remarkably resistant to oxidant-mediated cell detachment and cell lysis. In addition, we determined ATP levels, 3H-adenine release and 51chromium release in LLC-PK1, NHK-C and endothelial cells in the presence of superoxide dismutase to dismute superoxide anion, catalase to metabolize hydrogen peroxide, DMPO to trap hydroxyl radical and DMTU to scavenge hydrogen peroxide and hydroxyl radical. We found that catalase and DMTU (scavengers of hydrogen peroxide) provided significant protection from ATP depletion, prevented efflux of 3H-adenine metabolites and cell detachment while DMPO (scavenger of hydroxyl radical) prevented lytic injury. In addition, we found that the membrane-permeable iron chelator, phenanthroline, and preincubation with deferoxamine prevented cell detachment and cell lysis, confirming the role of hydroxyl radical in cell injury.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reactive oxygen molecule-mediated injury in endothelial and renal tubular epithelial cells in vitro. 217 55

An ethanol-induced oxidative stress is not restricted to the liver, where ethanol is actively oxidized, but can affect various extrahepatic tissues as shown by experimental data obtained in the rat during acute or chronic ethanol intoxication. Most of these data concern the central nervous system, the heart and the testes. An acute ethanol load has been reported to enhance lipid peroxidation in the cerebellum. This is accompanied by an increase in the cytosolic concentration of low-molecular-weight iron derivatives which may contribute to the generation of aggressive free radicals. The ethanol-induced decrease in the main antioxidant systems (superoxide dismutase, alpha-tocopherol, ascorbate and selenium) is a likely contributor to the cerebellar oxidative stress. Most of these disturbances can be prevented by allopurinol administration. Some experimental data support also the occurrence of pro- and anti-oxidant disturbances in the cerebellum and in other regions of the central nervous system after chronic ethanol administration. Chronic ethanol administration enhances lipid peroxidation in the heart. The increased conversion of xanthine dehydrogenase into xanthine oxidase as well as the activation of peroxisomal acyl CoA-oxidase linked to ethanol administration could contribute to the oxidative stress. Chronic ethanol administration elicits in the testes an enhancement in mitochondrial lipid peroxidation and a decrease in the glutathione level, which appear to be correlated to the gross testicular atrophy observed. Vitamin A supplementation attenuates the changes in lipid peroxidation, glutathione and testicular morphology. Whether the reported disturbances are involved in the pathogenesis of the tissue disorders observed in alcoholic patients remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues. 219 38

Oxygen-derived free radicals (ODFR) depolymerized synovial-fluid (SF) hyaluronic acid (HA) when hypoxanthine/xanthine oxidase (HX/XAO) was used as the radical generator. The molecular-weight distribution of ODFR-induced SF HA degradation products was determined using high performance liquid chromatography (HPLC) with TSK 5000 PW or TSK 6000 PW size-exclusion columns and simultaneously using 125I-labelled hyaluronate-binding protein (125I-HABP) assay. The exposure of SF HA to hydroxyl-radical flux resulted in the formation of a degradation product having a molecular weight of 13.5 X 10(3) daltons, from which no further degradation was achieved. If the iron chelator desferrioxamine and hydroxyl-radical scavenger mannitol were present in the reaction mixture, the HA peak decreased by 30-50%, as a result of reaction with superoxide radical and hydrogen peroxide. These results show that superoxide radical and hydroxyl radical may have different modes of action on SF HA. The molecular-weight distribution of serum HA from patients with rheumatoid arthritis varied in different individuals and ranged between 275 X 10(3) and 650 X 10(3).
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PMID:Reactive oxygen species and hyaluronate in serum and synovial fluid in arthritis. 221 Sep 71

The molybdenum center of xanthine oxidase has been examined by resonance Raman spectroscopy. Making use of the long-wavelength absorption of the reduced molybdenum center in complex with violapterin (the product of enzymic action of lumazine), resonance Raman spectra were obtained using laser excitation at 676.4 nm. Several internal vibrational modes of violapterin were found to be resonance-enhanced, and a number of bands in the 250-1100 cm-1 range, presumably arising from vibrational modes of the molybdenum coordination sphere, were also observed. Upon substitution of 18O for 16O in the molybdenum coordination sphere, bands at 1469, 853, 517, 325, and 276 cm-1 exhibited shifts of 5-12 cm-1 to lower energy. By analogy to previous vibrational studies of Mo-O-Mo and Mo-O-R model compounds, the 853, 517, and 276 cm-1 frequencies were judged consistent with a labeled Mo-O-R linkage of the complexed violapterin. More importantly, the relatively small frequency shifts observed in these and other vibrations upon incorporation of 18O are very similar to those observed by others for 18O-labeled phenol and metal-phenolate complexes (Pinchas, S., Sadeh, D., and Samuel, D. (1965) J. Phys. Chem. 69, 2259-2264; Pyrz, W. J., Rue, L. A., Stern, L. J., and Que, L. J., Jr. (1985) J. Am. Chem. Soc. 107, 614-620) that model iron-tyrosinate proteins. The relatively small isotope-induced frequency shifts in multiple bands are thus interpreted as resulting from vibrational mixing of internal coordinates involving the oxygen atom with internal ring motions of the aromatic species. No oxygen isotope-sensitive bands were observed in the 900-1100 cm-1 region where Mo = O stretching modes typically occur. In agreement with the conclusions of previous workers (Davis, M.D., Olson, J. S., and Palmer, G. (1982) J. Biol. Chem. 257, 14730-14737) we interpret our results to indicate that the absorption band appearing upon complexation of violapterin with the molybdenum center of reduced xanthine oxidase is a molybdenum-to-violapterin charge-transfer band. These results, as well as several other lines of evidence, are consistent with direct coordination of violapterin to molybdenum in the charge-transfer complex via the 7-hydroxyl group (i.e. the hydroxyl group introduced into substrate by the enzyme). The Mo=O stretching mode of the complex is presumably not resonance enhanced because it is orthogonal to the charge-transfer electronic transition, suggesting that coordination of violapterin is cis to the oxo group.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Resonance-enhanced Raman scattering from the molybdenum center of xanthine oxidase. 221 38

As revealed in experiments on V. cholerae, the enzymatic link xanthine oxidase-xanthine produces a vibriostatic effect at the concentration of xanthine oxidase equal to 0.0125 g/l and a vibriocidal effect at the concentration of xanthine oxidase equal to 0.025 g/l in a medium with pH 7.5-7.6. In the presence of protein the antivibrionic activity of the xanthine oxidase link is decreased. The introduction of bivalent iron into the enzymatic link xanthine oxidase-xanthine enhances its vibriocidal action on V. cholerae.
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PMID:[The antimicrobial action of the xanthine oxidase-xanthine system on the causative agent of cholera]. 223

Factors that potentially affect the generation of excess low molecular weight DNA (LMW-DNA) in cultured phytohemagglutinin (PHA)-stimulated lymphocytes of patients with systemic lupus erythematosus (SLE) were studied because this species of DNA is consistently found and this DNA may play a role in the pathogenesis of the disease. Superoxide dismutase (SOD; 0.05 mg/mL), a scavenger of free radical oxygen, decrease LMW-DNA formation in lymphocytes by 22%. Co-cultivation with cysteamine, a second scavenger of free radical oxygen and a sulfhydryl radioprotective agent, resulted in a 32% decrease in the generation of excess LMW-DNA at a concentration of 0.5 x 10(-3) mol/L and largely prevented its formation at 1.0 x 10(-3) mol/L. Other free radical scavengers (catalase, mannitol, vitamins C and E), cyclooxygenase inhibitors (ibuprofen and aspirin), a xanthine oxidase inhibitor (allopurinol), and an iron chelator (desferoxamine) did not affect excess LMW-DNA formation. Glutathione (1 x 10(-3) mol/L) had no effect and cysteine was toxic. Because scavengers of free radicals might be useful in the therapy of lupus, a trial of cysteamine (30 to 60 mg/kg/d) was administered to six acutely ill patients with SLE. A therapeutic benefit was not demonstrated, and some patients had exacerbation of disease. Lymphocyte cell growth from control and lupus subjects was stimulated when cysteamine, 1 x 10(-5) to 1 x 10(-4) mol/L was added to the media, but inhibited at concentrations of 2 x 10(-4) mol/L or greater. These studies suggest that the autooxidation and toxicity of high-dose cysteamine preclude its therapeutic use as a free radical scavenger.
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PMID:Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus. 224 68


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