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)

We have suggested that red blood cell proteolytic systems can degrade oxidatively damaged proteins, and that both damage and degradation are independent of lipid peroxidation (Davies, K. J. A., and Goldberg, A. L. (1987) J. Biol. Chem. 262, 8220-8226. These ideas have now been tested in cell-free extracts of rabbit erythrocytes and reticulocytes. Exposure to oxygen radicals or H2O2 increases the degradation of endogenous proteins in cell-free extracts, as in intact cells. Various radical-generating systems (acetaldehyde or xanthine + xanthine oxidase, ascorbic acid + iron, H2O2 + iron) and H2O2 alone enhanced the rates of proteolysis severalfold. Since these extracts were free of membrane lipids, protein damage and degradation must be independent of lipid peroxidation. An antioxidant buffer consisting of HEPES, glycerol, and dithiothreitol inhibited the increased proteolysis by 60-100%. Mannitol caused a 50-80% reduction in proteolysis suggesting that the hydroxyl radical (.OH), or a species with similar reactivity, may be the initiator of protein damage. When casein or bovine serum albumin were exposed to .OH (generated by H2O2 + Fe2+, or COCo radiation) these proteins were degraded up to 50 times faster than untreated proteins during subsequent incubations with red cell extracts. Mannitol inhibited this increase in proteolysis only if present during .OH exposure; mannitol did not affect the degradative system. Although ATP increased the degradation of untreated proteins 4- to 6-fold in reticulocyte extracts, it had little or no effect on the degradation of proteins exposed to .OH. ATP also did not stimulate hydrolysis of .OH-treated proteins in erythrocyte extracts. Leupeptin did not affect the degradative processes in either extract; thus lysosomal or Ca2+-activated thiol proteases were not involved. We propose that red cells contain a soluble, ATP-independent proteolytic pathway which may protect against the accumulation of proteins damaged by .OH or other active oxygen species.
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PMID:Proteins damaged by oxygen radicals are rapidly degraded in extracts of red blood cells. 359 73

A homogeneous preparation of transketolase was obtained from spinach leaf; the specific enzyme activity was 9.5 mumolo of glyceraldehyde-3-P formed (mg of protein)-1 min-1, when xylulose-5-P and ribose-5-P were used as the donor and acceptor, respectively, of the ketol residue. Transketolase catalyzed the formation of glycolate from fructose-6-P coupled with the O2- -generating system of xanthine-xanthine oxidase. The addition of superoxide dismutase (145 units) or 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron) (5 mM), both O2- scavengers, to the reaction system inhibited glycolate formation 72 and 58%, respectively. The reacton was not inhibited by catalase. Mannitol, an .OH scavenger, and beta-carotene and 1,4-diazobicyclo[2.2.2]octane, 1O2 scavengers, showed little or no inhibitory effects. The rate of glycolate formation catalyzed by the transketolase system was measured in a coupled reaction with a continuous supply of KO2 dissolved in dimethyl sulfoxide, used as an O2- -generating system. The optimum pH of the reaction was above pH 8.5. The second-order rate constant for the reaction between transketolase and O2-, determined by the competition for O2- between nitroblue tetrazolium (NBT) and transketolase, was 1.0 X 10(6) M-1 s-1. Transketolase showed an inhibitory effect on the O2- -dependent reduction of NBT only if the reaction mixture was previously incubated with ketol donors such as fructose-6-P, xylulose-5-P, or glycolaldehyde. The results suggest the possibility that transketolase catalyzes O2- -dependent glycolate formation under increased steady-state levels of O2- in the chloroplast stroma.
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PMID:Glycolate formation catalyzed by spinach leaf transketolase utilizing the superoxide radical. 625 May 80

Generation of oxygen free radicals by xanthine acting on xanthine oxidase as a substrate significantly depressed calcium transport by sarcoplasmic reticulum in canine whole heart homogenates at 37 degrees C. At pH 7.0, this effect was completely inhibited by the addition of superoxide dismutase (SOD), a scavenger of the superoxide anion radical. At pH 6.4, SOD (5 to 20 micrograms X ml-1) was ineffective but catalase (20 micrograms X ml-1) was able to inhibit the effects of the xanthine-xanthine oxidase system. SOD + catalase (20 micrograms X ml-1) and SOD + mannitol, a scavenger of the hydroxyl free radical, inhibited the effects of the xanthine-xanthine oxidase system at pH 6.4. Preincubation at pH 6.4, in the absence of an exogenous free radical generating system, depressed calcium transport. This depression was more severe the longer the duration of incubation. However, return of the pH to 7.0 after preincubation at pH 6.4 partially restored calcium uptake velocity. The degree of reversibility was decreased the longer the period of incubation at pH 6.4. SOD reversed the effects of incubation at pH 6.4 for 5 min, but not those for incubations of 10 and 15 min. Mannitol alone was ineffective. The combinations of SOD and mannitol significantly reversed the effects of pH 6.4 up to 15 min. These results demonstrate that both exogenously generated and endogenously generated free oxygen radicals are capable of depressing calcium transport by cardiac sarcoplasmic reticulum in the whole heart homogenate in the presence of endogenous scavenging systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates. 632 91

The effects of a range of free-radical scavenging drugs on luminol-enhanced chemiluminescence (CL) generated by porcine leukocytes, following activation by two nonreceptor-mediated stimulants, phorbol myristate acetate (PMA; a protein kinase activator) and ionomycin (a cation ionophore), and by xanthine plus xanthine oxidase (X-XO), have been examined. Superoxide dismutase (0.1 units/mL) and catalase (50 units/mL) inhibited X-XO, but they were ineffective in leukocyte suspensions except at concentrations 500 times and 20 times higher. Sodium azide (10(-5) to 10(-3) M) caused a marked inhibition in CL production in activated leukocytes, but not of X-XO CL. The antioxidants, glutathione (10(-3) M) and L-ascorbic acid (10(-3) M) were ineffective in activated leukocytes, but caused total inhibition of X-XO-induced CL. Mannitol (100 mM) had no effect on chemiluminescence in either system. Captopril (10(-3) M) produced an inhibition of CL in both systems and this inhibition was significantly modified by pH. Thus, the present study has established a standard screening procedure for the assessment of free-radical scavenging activity using activated porcine leukocytes and xanthine-xanthine oxidase.
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PMID:Characterization of a method for the detection of drugs with free radical scavenging activity using porcine leukocytes. 783 5

Combined stimulation, by superoxide ions generated by the xanthine-xanthine oxidase reaction, and platelet-activating factor (PAF), induced cell differentiation of rat monocytic leukemia cells (c-WRT-LR) to macrophage-like mature cells. Monitoring of cytochrome c reduction revealed that PAF stimulation induced the release of superoxide ions from c-WRT-LR. To further investigate the effect of superoxide ions in the autocrine or paracrine mechanism in cell differentiation, molecular species of the oxygen radicals under PAF stimulation were examined using the EPR spin trap, 5,5'-dimethyl-1-pyrroline N-oxide (DMPO). PAF and/or phorbol myristate acetate caused the formation of EPR spectra, a combination of DMPO/.OOH and DMPO/.OH. Since both spectra were diminished in the presence of superoxide dismutase, it was concluded that DMPO/.OH was derived from superoxide ions. Mannitol and catalase suppressed cell differentiation induced by combined stimulation with PAF and oxygen radicals generated by the xanthine-xanthine oxidase reaction. Taken together, these results suggest that hydroxyl radicals generated by Fenton reaction from H2O2 may be involved in the mechanism of cell differentiation in rat monocytic leukemia cells.
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PMID:A role for oxygen radicals in rat monocytic leukemia cell differentiation under stimulation with platelet-activating factor. 830 1

To understand the influence of oxidant stress on the barrier function of airway epithelium, we conducted studies to determine the effects of chemically generated reactive oxygen species on permeability, permselectivity, and active ion transport of ferret trachea. We examined the consequences of oxidant injury using ferret trachea mounted in Ussing-type chambers and bathed with a modified Krebs-Henseleit solution containing mannitol and xanthine. We added xanthine oxidase to the luminal bathing solution, which reacted with the xanthine to generate reactive oxygen species. Tissue electrical conductance and short-circuit current were significantly increased after the addition of xanthine oxidase. Simultaneous measurement of mannitol flux (as a marker of paracellular conductance) and the backflux of chloride (lumen to submucosa) demonstrated a significant oxidant-induced increase in mannitol flux and backflux of chloride. Mannitol flux and the backflux of sodium (submucosa to lumen) also increased after oxidant stress. Comparison of the diffusion of sodium relative to the diffusion of chloride in relation to predicted diffusion in free solution indicated that the paracellular pathway was cation selective after oxidant stress. Active ion transport, as reflected by the short-circuit current, was significantly increased transiently after oxidant stress. Studies with furosemide, amiloride, and diphenylamine-2-carboxylate are suggestive that oxidant stress transiently stimulates the Na-K-ATPase. These studies demonstrated that exposure to reactive oxygen species significantly altered the permeability of the tracheal epithelium as well as active ion transport.
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PMID:Oxidant injury alters barrier function of ferret tracheal epithelium. 844 29

Various tissues of the marine bivalve Mytilus galloprovincialis were analysed histochemically for oxidases capable of generating reactive oxygen species (ROS) using the cerium-DAB technique. Incubations were performed on unfixed cryostat sections using polyvinyl alcohol and semipermeable membranes. High xanthine oxidoreductase and D-amino acid oxidase (DAOX) activities were observed in kidney epithelial cells of mussels. DAOX also presented a strong activity in all the digestive epithelia. No xanthine oxidase activity was observed in any of the mussel tissues tested suggesting the presence of an enzyme only showing dehydrogenase activity. Mannitol oxidase, associated with special organelles called 'mannosomes' of terrestrial gastropods, presented a weak activity in the stomach epithelium and a strong specific activity in the haemocytes. Only DAOX presented a discrete granular distribution compatible with a peroxisomal compartmentalization. No urate oxidase activity could be demonstrated in tissues of mussels. These observations suggest a role for peroxisomes in ROS generation and determine the tissues capable of producing oxygen radicals in the digestive gland. This study raises the question of the behaviour of these enzymes in conditions in which ROS-generating organic xenobiotics are accumulated in the digestive gland of molluscs.
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PMID:Histochemistry of oxidases in several tissues of bivalve molluscs. 957 Aug 92

We had previously studied different modes of prevention of liver ischemia-reperfusion (IR)-induced remote organ reperfusion injury, a challenge that remains partly unmet. We have now studied the capability of mannitol at different doses in abrogating liver IR-induced lung reperfusion injury in an isolated double-organ model. Rat livers ( n = 8/group) were perfused with Krebs-Henseleit solution (control) or made globally ischemic (IR) for 2 h, after which they were paired with normal lungs and "reperfused" together for 15 min. The lungs were then perfused alone with the accumulated Krebs for an additional 45 min. Another 4 control and 4 IR pairs were reperfused with Krebs containing mannitol at.22 mmol,.55 mmol,.77 mmol, or 1.1 mmol. Mannitol.22 mmol and 1.1 mmol failed to attenuate IR-lung injury as indicated by 50-95% increases in inspiratory and perfusion pressures and compliance reduction, a 70% increase in weight gain, and a 2-50-fold increase in bronchoalveolar lavage volume and content. Mannitol.55 mmol prevented all these abnormalities, and.77 mmol attenuated only changes in ventilatory parameters. The latter two treatments were also associated with a 50% reduction in xanthine oxidase activity and a 35-45% increase in the reduced glutathione tissue content compared with the nontreated IR-paired lungs. It is concluded that mannitol in a narrow therapeutic dose range can reduce oxidalive stress-induced lung damage that is related to liver IR.
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PMID:Mannitol dose-dependently attenuates lung reperfusion injury following liver ischemia reperfusion: a dose-response study in an isolated perfused double-organ model. 1264 34

We examined if phytic acid inhibits the enzymatic superoxide source xanthine oxidase (XO). Half inhibition of XO by phytic acid (IC50) was about 30 mM in the formation of uric acid from xanthine, but generation of the superoxide was greatly affected by phytic acid; the IC50 was about 6 mM, indicating that the superoxide generating domain of XO is more sensitive to phytic acid. The XO activity in intestinal homogenate was also inhibited by phytic acid. However, it was not observed with intestinal homogenate that superoxide generation was more sensitive to phytic acid compared with the formation of uric acid as observed with XO from butter milk. XO-induced superoxide-dependent lipid peroxidation was inhibited by phytic acid, but not by myo-inositol. Reduction of ADP-Fe3+ caused by XO was inhibited by superoxide dismutase, but not phytic acid. The results suggest that phytic acid interferes with the formation of ADP-iron-oxygen complexes that initiate lipid peroxidation. Both phytic acid and myo-inositol inhibited XO-induced superoxide-dependent DNA damage. Mannitol inhibited the DNA strand break. Myo-inositol may act as a hydroxyl radical scavenger. The antioxidative action of phytic acid may be due to not only inhibiting XO, but also preventing formation of ADP-iron-oxygen complexes.
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PMID:Inhibition of xanthine oxidase by phytic acid and its antioxidative action. 1473 12


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