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 effects of cimetidine, ranitidine, histamine and histidine, as well as of their copper complexes, have been examined in an enzymic and chemical O2- generated systems. Copper complexes like CuZnSOD inhibited both the reduction of cytochrome c and NBT2+ in xanthine-xanthine oxidase systems, but their inhibitory action was due to a certain extent to the copper-induced inhibition of xanthine oxidase. EDTA abolished the inhibitory effect of all copper complexes studied. Luminol chemiluminescence in NADH2-PMS system was inhibited by CuZnSOD while it was enhanced by copper complexes. The copper-accelerating effect gradually increased up to about 1 microM Cu and decreased, reaching the control values up to 10 microM Cu. In the presence of low copper concentrations chemiluminescence was inhibited by CuZnSOD only, while in the presence of high copper concentrations it was inhibited by catalase and mannitol, but not by CuZnSOD. The ligands however, have been ineffective in the two O2- generated systems.
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PMID:Do the copper complexes of histamine, histidine and of two H2-antagonists react with O2-? 167 75

Activated neutrophils and possibly xanthine oxidase-derived free radicals are believed to be mediators of ischemia and reperfusion-induced myocardial damage. We studied the cardioprotective effect of the neutrophil stabilizer and xanthine oxidase inhibitor azapropazone in dogs subjected to thrombotic occlusion of the left anterior descending coronary artery (LAD), induced by intracoronary introduction of a copper coil, followed 60 min later by thrombolytic treatment with intracoronary streptokinase and 4-day reperfusion; we then determined infarct size by triphenyltetrazolium stain. Azapropazone [100 mg/kg intravenously (i.v.) followed by a 24-h i.v. infusion of 10 mg/kg/h, n = 8] or vehicle (n = 10) treatments were started immediately before the streptokinase infusion. Steady-state plasma levels of azapropazone ranged from 97 to 163 micrograms/ml during the infusion. Myocardial blood flow and underperfused area at risk were determined using radiolabeled microspheres. Results were as follows (mean +/- SEM): area at risk (percentage of left ventricle) azapropazone 22.7 +/- 3.16 and vehicle 21.8 +/- 4.13; infarct size (percentage of area at risk), azapropazone 45.1 +/- 11.8 and vehicle 75.7 +/- 10.6, p less than 0.03; collateral blood flow (ml/min/g), azapropazone 0.27 +/- 0.02 and vehicle 0.23 +/- 0.02; total ischemic period (min), azapropazone 106 +/- 5.9 and vehicle 91.5 +/- 4.9. Azapropazone had no effects on heart rate (HR), blood pressure (BP), or rate/pressure product (RPP). These dta show that azapropazone limits infarct size in a canine model of coronary thrombosis and long-term reperfusion and that this cardioprotection is independent of cardiovascular parameters.
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PMID:Persistent cardioprotection by azapropazone in a canine model of coronary artery thrombosis and thrombolysis. 171 99

The therapy of copper poisoning with mercaptodextran inhibits the copper-induced haemolysis, whereas 2,3- dimercaptopropanesulfonic acid (DMPS) may accelerate such haemolysis. Some aspects of the mechanisms of these effects were investigated. The possible generation of activated oxygen species during the interaction of Cu++ and chelating thiols was studied using a chemoluminiscent method detecting oxygen radicals. It was found that incubation of DMPS with copper ions or erythrocyte membranes was accompanied by generation of oxygen radicals. Mercaptodextran added to similar suspensions did not lead to oxygen radical production. And unlike DMPS, mercaptodextran acted as a scavenger of radicals generated by the xanthine oxidase/acetaldehyde system. The different ability of the chelating thiols to cope with free radicals may explain their different potentials to protect against copper-induced haemolysis. Our results also indicate that mercaptodextran may be a useful therapeutic agent in cases of haemolytic crisis in Wilson's disease.
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PMID:Mercaptodextran--a new copper chelator and scavenger of oxygen radicals. 171 13

In this paper we have investigated whether or not superoxide dismutase is localized in peroxisomes from rat liver. Using an improved method to prepare peroxisomes from clofibrate induced rat livers, we identified superoxide dismutase activity in peroxisomes. This activity was found to be predominantly of the copper-zinc type. The finding of superoxide dismutase activity in peroxisomes makes sense since peroxisomes also contain superoxide generating enzyme activities such as xanthine oxidase.
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PMID:Identification of superoxide dismutase in rat liver peroxisomes. 173 41

We have demonstrated the selective induction of manganese superoxide dismutase (MnSOD) or catalase mRNA after exposure of tracheobronchial epithelial cells in vitro to different oxidant stresses. Addition of H2O2 caused a dose-dependent increase in catalase mRNA in both exponentially growing and confluent cells. A 3-fold induction of catalase mRNA was seen at a nontoxic dose of 250 microM H2O2. Increase in the steady-state mRNA levels of glutathione peroxidase (GPX) and MnSOD were less striking. Expression of catalase, MnSOD, and GPX mRNA was highest in confluent cells. In contrast, constitutive expression of copper and zinc SOD (CuZnSOD) mRNA was greatest in dividing cells and was unaffected by H2O2 in both exponentially growing and confluent cells. MnSOD mRNA was selectively induced in confluent epithelial cells exposed to the reactive oxygen species-generating system, xanthine/xanthine oxidase, while steady-state levels of GPX, catalase, and CuZnSOD mRNA remained unchanged. The 3-fold induction of MnSOD mRNA was dose-dependent, reaching a peak at 0.2 unit/ml xanthine oxidase. MnSOD mRNA increases were seen as early as 2 h and reached maximal induction at 24 h. Immunoreactive MnSOD protein was produced in a corresponding dose- and time-dependent manner. Induction of MnSOD gene expression was prevented by addition of actinomycin D and cycloheximide. These data indicate that epithelial cells of the respiratory tract respond to different oxidant insults by selective induction of certain antioxidant enzymes. Hence, gene expression of antioxidant enzymes does not appear to be coordinately regulated in these cell types.
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PMID:Differential regulation of antioxidant enzymes in response to oxidants. 176 41

In sheep from biogeochemical provinces enriched by molybdenum and copper and in a model form of molybdenum toxicosis in animals, the important role of enzymic and neurohumoral systems in the development of adaptation to excessive uptake of molybdenum and copper has been demonstrated. Adaptive reorganization of the activity of enzymic systems (xanthine oxidase, ceruloplasmin, succinate dehydrogenase, aspartate and alanine aminotransferases) and gradual involvement of neurohumoral mechanisms of the sympathoadrenal and cholinoreactive systems provide for adaptation of some animals in molybdenum and copper-molybdenum biogeochemical provinces. In other sheep, under the same conditions, dystonic disturbances in the vegetative nervous systems are observed together with the development of molybdenum toxicosis.
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PMID:[The enzymatic chemical mechanisms of adaptation]. 183 7

Mixtures of Cu2+ and H2O2 at pH 7.4 caused damage to the bases in DNA greater than that caused by mixtures of Fe3+ and H2O2. Addition of ascorbic acid to the Cu2+/H2O2 system caused a very large increase in base damage, much greater than that produced by the Fe3+/H2O2/ascorbic acid system. The products of base damage in the presence of Cu2+ were typical products that have been shown to result from attack of hydroxyl radicals upon the DNA bases. Cytosine glycol, thymine glycol, 8-hydroxyadenine and especially 8-hydroxyguanine were the major products in both the Cu2+/H2O2 and the Cu2+/H2O2/ascorbic acid systems. Base damage in DNA by these systems was inhibited by the chelating agents EDTA and nitrilotriacetic acid and by catalase, but not by superoxide dismutase, nor by the hydroxyl-radical scavenger mannitol. It is proposed that Cu2+ ions bound to the DNA react with H2O2 and ascorbic acid to generate hydroxyl radicals, which then immediately attack the DNA bases in a site-specific manner. A hypoxanthine/xanthine oxidase system also caused damage to the DNA bases in the presence of Cu2+ ions. This was inhibited by superoxide dismutase and catalase. The high activity of Cu2+ ions, when compared with Fe3- ions, in causing hydroxyl-radical-dependent damage to DNA and to other biomolecules, means that the availability of Cu2+ ions in vivo must be carefully controlled.
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PMID:Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide. 189 97

Uric acid is an end-product of purine metabolism in Man, and has been suggested to act as an antioxidant in vivo. Products of attack upon uric acid by various oxidants were measured by high performance liquid chromatography. Hypochlorous acid rapidly oxidized uric acid, forming allantoin, oxonic/oxaluric and parabanic acids, as well as several unidentified products. HOCl could oxidize all these products further. Hydrogen peroxide did not oxidize uric acid at detectable rates, although it rapidly oxidized oxonic acid and slowly oxidized allantoin and parabanic acids. Hydroxyl radicals generated by hypoxanthine/xanthine oxidase or Fe2(+)-EDTA/H2O2 systems also oxidized uric acid to allantoin, oxonic/oxaluric acid and traces of parabanic acid. Addition of ascorbic acid to the Fe2(+)-EDTA/H2O2 system did not increase formation of oxidation products from uric acid, possibly because ascorbic acid can 'repair' the radicals resulting from initial attack of hydroxyl radicals upon uric acid. Mixtures of methaemoglobin or metmyoglobin and H2O2 also oxidized uric acid: allantoin was the major product, but some parabanic and oxonic/oxaluric acids were also produced. Caeruloplasmin did not oxidize uric acid under physiological conditions, although simple copper (Cu2+) ions could, but this was prevented by albumin or histidine. The possibility of using oxidation products of uric acid, such as allantoin, as an index of oxidant generation in vivo in humans is discussed.
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PMID:Action of biologically-relevant oxidizing species upon uric acid. Identification of uric acid oxidation products. 215 12

Red blood cells (RBC) are thought to be well protected against oxidative stress by the antioxidant, cu-pro-zinc enzyme superoxide dismutase (CuZn SOD) which dismutates O2- to H2O2. CuZn SOD, however, is irreversibly inactivated by its product H2O2. Exposure of intact RBC to H2O2 resulted in the inactivation (up to 50%) of endogenous SOD in a concentration-dependent manner. When RBC were exposed to O2- and H2O2, generated by xanthine + xanthine oxidase, an even greater loss of SOD activity (approximately 75%) was observed. Intracellular proteolysis was markedly increased by exposure to these same oxidants; up to a 12-fold increase with H2O2 and a 50-fold increase with xanthine oxidase plus xanthine. When purified SOD was treated with H2O2, inactivation of the enzyme also occurred in a concentration-dependent manner. Accompanying the loss of SOD activity, the binding of the copper ligand to the active site of the enzyme diminished with H2O2 exposure, as evidenced by an increase in accessible copper. Significant direct fragmentation of SOD was evident only under conditions of prolonged exposure (20 h) to relatively high concentrations of H2O2. Gel electrophoresis studies indicated that under most experimental conditions (i.e. 1-h incubation) H2O2, O2-, and H2O2 + O2- treated SOD experienced charge changes and partial denaturation, rather than fragmentation. The proteolytic susceptibility of H2O2-modified SOD, during subsequent incubation with (rabbit, bovine or human) red cell extracts also increased as a function of pretreatment with H2O2. Both enzyme inactivation and altered copper binding appeared to precede the increase in proteolytic susceptibility (whether measured as an effect of H2O2 concentration or as a function of the duration of H2O2 exposure). These results suggest that SOD inactivation and modification of copper binding are prerequisites for increased protein degradation. Proteolytic susceptibility was further enhanced by H2O2 exposure under alkaline conditions, suggesting that the hydroperoxide anion is the damaging species rather than H2O2 itself. In RBC extracts, the proteolysis of H2O2-modified SOD was inhibited by sulfhydryl reagents, serine reagents, transition metal chelators, and ATP; suggesting the existence of an ATP-independent proteolytic pathway of sulfhydryl, serine, and metalloproteases, and peptidases. The proteolytic activity was conserved in a "Fraction II" of both human and rabbit RBC, and was purified from rabbit reticulocytes and erythrocytes to a 670-kDa proteinase complex, for which we have suggested the trivial name macroxyproteinase. In erythrocytes macroxyproteinase may prevent the accumulation of H2O2-modified SOD.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Superoxide dismutase undergoes proteolysis and fragmentation following oxidative modification and inactivation. 219 28

Dietary fat-type and copper (Cu) deficiency have been independently identified as potentially important factors in the etiology of ischemic heart disease (IHD); a disease that has been linked to inflammation and oxygen free radical (OFR) mediated damage. Group (n = 6) of male, weanling, Wistar rats were provided ad libitum with deionized water and control or low Cu diets containing (200 g/kg) either saturated or polyunsaturated fatty acids (SFA or PUFA, respectively) for 56 d. Measurement of several indices of Cu status indicated that both groups fed the low Cu diets were Cu-deficient. SFA consumption resulted in significantly increased hepatic Cu (p less than 0.001) and iron (Fe) (p less than 0.001) concentrations and xanthine oxidase activity (p less than 0.05) and significantly decreased hepatic glucose-6-phosphate dehydrogenase activity (p less than 0.001). Although Cu deficiency resulted in significantly decreased hepatic copper-zinc superoxide dismutase (CuZnSOD) activity (p less than 0.01), no significant effect on the activities of the other hepatic antioxidant enzymes, manganese superoxide dismutase, catalase, and glutathione peroxidase, or glutathione reductase, were observed. Cu deficiency also resulted in significantly decreased hepatic Cu levels (p less than 0.001) and cytochrome c oxidase activity (p less than 0.01). No significant difference in hepatic thiobarbituric acid reactive substances (TBARS), a measure of lipid peroxidation, was found between groups consuming SFA or PUFA, but both Cu-deficient groups exhibited significantly increased hepatic TBARS (p less than 0.001), compared to controls. This was probably owing to the significantly decreased hepatic CuZnSOD activity observed in the Cu-deficient, compared to control animals.
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PMID:Dietary saturated or polyunsaturated fat and copper deficiency in the rat. 248 34


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