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)

Indoleamine 2,3-dioxygenase purified to apparent homogeneity from rabbit intestine was inhibited by scavengers for superoxide anion such as superoxide dismutase and 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron). On the other hand, beta-carotene and 1,4-diazobicyclo-(2,2,2)-octane, scavengers for singlet oxygen, did not affect the enzyme activity significantly. The degree of inhibition of the dioxygenase by superoxide dismutase preparations from bovine erythrocytes, green peas, spinach leaves, and Escherichia coli paralleled that observed with these dismutase preparations on the aerobic reduction of cytochrome c by xanthine oxidase and its substrate. The pH profiles of the inhibition by dismutase of the dioxygenase and cytochrome c reduction were also similar and the maximal inhibition was observed around pH 10 in both cases. The degree of inhibition was not affected by the concentration of substrate but was a function of the concentration of dismutase. It was inversely related to the concentrations of the dioxygenase and its cofactors, ascorbic acid and methylene blue, both of which were required for maximum activity. Ascorbic acid could be replaced either by xanthine oxidase and its substrate, or by tetrabutylammonium superoxide prepared by electrolytic reduction of molecular oxygen, or by potassium superoxide. When limited amounts of superoxide anion were added to the reaction mixture containing a substrate amount of the dioxygenase, the ratio of the amount of superoxide anion added to that of the product formed was approximately unity both under aerobic and anaerobic conditions. Taken together, these findings indicate that superoxide anion, rather than molecular oxygen, is utilized as substrate by indoleamine 2,3-dioxygenase.
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PMID:Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate. 23 93

The chemiluminescence of isolated neutrophils, stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine, latex, lipopolysaccharide from Escherichia coli, zymosan A, or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate was inhibited up to 99% by the dose-dependent oxygen radical scavenging activity of 6 mmol/l ascorbic acid. The chemiluminescence of neutrophils in blood, stimulated with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, or with zymosan A was inhibited 35% or 48%, respectively, by 6 mmol/l ascorbic acid. Ascorbic acid, up to 6 mmol/l, did not inhibit the release of beta-N-acetylglucosaminidase and elastase from isolated neutrophils activated by the above stimulatory agents. During neutrophil/nylon fibre interaction ascorbic acid reduced the oxygen radical production dose-dependently (77% inhibition of the chemiluminescence response at 6 mmol/l ascorbic acid), whereas the adherence was unaffected. Hypoxanthine/xanthine oxidase-generated oxygen radicals were scavenged by ascorbic acid in a dose-dependent manner (99% inhibition of the chemiluminescence response at 100 mumol/l ascorbic acid). From these results, ascorbic acid can highly be recommended for animal experiments and clinical studies in patients with trauma, shock and sepsis and for studies to prevent or reduce reperfusion injuries.
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PMID:Effect of ascorbic acid on neutrophil functions and hypoxanthine/xanthine oxidase-generated, oxygen-derived radicals. 152 46

Present work describes a new property of HDL to act as a scavenger of O2- free radicals in vitro. This lipoprotein prevents both enzymic and non-enzymic generation of O2- anions as evidenced by inhibition of xanthine oxidase, peroxidase, peroxidation of pyrogallol and phenazine methosulphate-NADH reaction. Ascorbate stimulated MDA formation in microsomes has been shown to be suppressed by HDL and these effects are comparable with that of BHA.
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PMID:High density lipoprotein is a scavenger of superoxide anions. 217 36

We have studied the scavenging effects of different structures and configurations of schizandrins isolated from Fructus Schizandrae, a traditional Chinese herb, on active oxygen radicals with the method of spin-trapping technique. The active oxygen radicals were produced from human polymorphonuclear leukocytes (PMN) stimulated with phorbol myristate acetate (PMA). In addition, the scavenging effects of schizandrins on hydroxyl radicals (.OH) in Fenton's reaction and the scavenging effects on superoxide anions (O2-.) in both riboflavin/EDTA and xanthine/xanthine oxidase systems have also been studied. They are compared with the scavenging effects of both Vitamin C (Vc) and Vitamin E (VE). The experimental results have shown that the scavenging effect of schizandrin B (Sin B) on the active oxygen radicals is stronger than that of S(-) Sin B and R(+) Sin B. For schizandrins of the same molecular structures with different stereoconfigurations the scavenging effects of S type of the benzene ring on active oxygen radicals are stronger than those of R type and for schizandrins of the same stereoconfigurations with different structures the scavenging effects of schizandrin C (Sin C) on the active oxygen radicals are stronger than those of Sin B.
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PMID:Scavenging effects on active oxygen radicals by schizandrins with different structures and configurations. 217 1

S-thiolation of cardiac creatine kinase and skeletal muscle glycogen phosphorylase b was initiated by reduced oxygen species in reaction mixtures containing reduced glutathione. Both proteins were extensively modified at similar rates under conditions in which the oxidation of glutathione was inadequate to cause S-thiolation by thiol-disulfide exchange. Creatine kinase was both S-thiolated and non-reducibly oxidized at the same time at low glutathione concentration. The amount of each modification was decreased by adding additional reduced glutathione, and with adequate glutathione oxidation was prevented while S-thiolation was still very active. S-thiolation of glycogen phosphorylase b was not significantly affected by glutathione concentration and non-reducible oxidation of glycogen phosphorylase b was not observed. These experiments suggest that oxyradical or H2O2-initiated processes may be an important mechanism of protein S-thiolation during oxidative stress, and that the cellular concentration of glutathione may be an important factor in S-thiolation of different proteins. Both creatine kinase and glycogen phosphorylase b competed favorably with ferricytochrome c for superoxide anion in the standard xanthine oxidase system for the generation of oxyradicals and H2O2. These proteins were as effective as ascorbate and much more effective than reduced glutathione in this regard. Ascorbate was also an effective inhibitor of oxyradical-initiated S-thiolation of creatine kinase, suggesting a role of superoxide anion in protein S-thiolation. Other experiments showed that both catalase and superoxide dismutase could partially inhibit protein S-thiolation. Thus, reduced oxygen species may react with protein sulfhydryls resulting in S-thiolation by a mechanism that involves the reaction of an activated protein thiol with reduced glutathione.
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PMID:S-thiolation of creatine kinase and glycogen phosphorylase b initiated by partially reduced oxygen species. 282 73

Exposure of red blood cells to oxygen radicals can induce hemoglobin damage and stimulate protein degradation, lipid peroxidation, and hemolysis. To determine if these events are linked, rabbit erythrocytes were incubated at 37 degrees C with various oxygen radical-generating systems and antioxidants. Protein degradation, measured by the production of free alanine, increased more than 11-fold in response to xanthine (X) + xanthine oxidase (XO). A similar increase in proteolysis occurred when the cells were incubated with acetaldehyde plus XO, with ascorbic acid plus iron (Asc + Fe), or with hydrogen peroxide (H2O2) alone. Upon addition of XO, increased proteolysis was evident within 5 min and was linear for up to 5 h. In contrast, lipid peroxidation, as shown by the production of malonyldialdehyde, conjugated dienes, or lipid hydroperoxides was observed only after 2 h of incubation with X + XO, acetaldehyde + XO, or H2O2. Ascorbate plus Fe2+ induced both protein degradation and lipid peroxidation; however, the addition of various antioxidants (urate, xanthine, glucose, or butylated hydroxytoluene) decreased lipid peroxidation without affecting proteolysis. Thus, these processes seem to occur by distinct mechanisms. Furthermore, at low concentrations of XO, protein degradation was clearly increased in the absence of detectable lipid peroxidation products. Hemolysis occurred only in a small number of cells (9%) and followed the appearance of lipid peroxidation products. Thus, an important response of red cells to oxygen radicals is rapid degradation of damaged cell proteins. Increased proteolysis seems to occur independently of membrane damage and to be a more sensitive indicator of cell exposure to oxygen radicals than is lipid peroxidation.
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PMID:Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes. 359 72

When Escherichia coli was incubated with xanthine oxidase and acetaldehyde, the killing of E. coli was accelerated by iron-EDTA but inhibited by hematin or hemoglobin. On the other hand, when E. coli was incubated with human neutrophils in the presence of phorbol myristate acetate (PMA), all of these iron species at concentrations of a few micromolar accelerated the inactivation of neutrophils and in so doing protected the E. coli from being killed by the neutrophils. The inactivation of the neutrophils was accompanied by an increase in lipid peroxidation and by a decrease in viability measured with trypan blue. This inactivation was inhibited by scavengers such as deoxyribose, mannitol, or thiourea. Desferrioxamine B and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) both inhibited the inactivation mediated by iron-EDTA, but had no effect on the hematin- or hemoglobin-mediated inactivation. Vanadium (vanadyl ion), an effective Fenton reagent, behaved in the same way as iron-EDTA relative to the effects of DMPO on neutrophil inactivation. These results led us to conclude that neutrophils were inactivated during PMA stimulation by OH radicals in the presence of iron-EDTA and by some other oxidizing species when hematin or Hb is present. Ascorbate enhanced the inactivation of neutrophils mediated by these iron species. Catalase was very effective in inhibiting neutrophil inactivation. Superoxide dismutase was not as effective but the combination with catalase was most effective.
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PMID:The effect of hemoglobin, hematin, and iron on neutrophil inactivation in superoxide generating systems. 813 43

The male and female reproductive systems are targets for the toxicity of a wide range of compounds. There is a paucity of information regarding the modulating effects of antioxidants in such systems. Enzymically generated oxygen radicals have been shown to be toxic and/or mutagenic in a variety of in vitro test systems. It is known that vitamins C and E can modify responses in such systems. Malformations and growth reductions have been observed in whole rat embryo cultures in this laboratory after treatment with the oxygen radical generating system of xanthine/xanthine oxidase. Groups of 9.5-day-old rat embryos were treated with this system with or without vitamin C or E. Vitamin C at the doses given totally abolished neural suture defects while vitamin E only partially did so. Vitamins C and E administered alone had no effect on the embryos. Germ cell detachment has been shown to occur in mixed cultures of Sertoli and germ cells in response to some known in vivo testicular toxins. Such cultures were also treated with the oxygen radical generating system of xanthine/xanthine oxidase. There was an increase in germ cell detachment with this treatment which was reduced by vitamin C but not by vitamin E at the doses administered. These findings would suggest that vitamin supplementation could protect somatic cells of reproductive systems against toxins that act through oxygen radical mechanisms.
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PMID:The modulating effects of antioxidants in rat embryos and Sertoli cells in culture. 830 31

Nitric oxide release is induced in many cells, including vascular endothelium, as part of the host response to inflammation. Nitric oxide synthase activity is increased in patients with sepsis, associated with increased oxidant demands and decreased antioxidant protection. We used a human vascular endothelial cell line to investigate the influence of antioxidants on nitric oxide synthase activity. Cells were cultured to confluence and incubated with interferon gamma, tumor necrosis factor, and lipopolysaccharide in the combined presence of the antioxidants ascorbic acid, Trolox, catalase, or superoxide dismutase, singly and in combination, for 48 h. Additionally, some cells were incubated with hypoxanthine-xanthine oxidase or a nitric oxide donor. Nitric oxide synthase activity was upregulated by cytokine exposure (p < .0005). Ascorbic acid and superoxide dismutase/ catalase resulted in decreased enzyme activity (p < .05). Superoxide anion release from xanthine oxidase caused increased activity (p < .05) and exogenous nitric oxide tended to suppress synthase activity. We suggest that antioxidants scavenge superoxide anion, enabling feedback inhibition of nitric oxide synthase activity by nitric oxide, and thus reducing enzyme activity. Exogenous nitric oxide also has a similar effect. Superoxide generation suppresses this feedback inhibition. This study has important implications in patients with sepsis in whom nitric oxide synthase inhibitor therapy is currently under investigation.
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PMID:Regulation of nitric oxide synthase activity in cultured human endothelial cells: effect of antioxidants. 879 Oct 97

The bioactivity of nitric oxide (.NO) depends, in part, on its interaction with superoxide. Usually, superoxide dismutase (SOD) preserves .NO bioactivity by limiting the availability of superoxide. Ascorbic acid also effectively scavenges superoxide, but the extent to which this interaction is necessary for intact .NO bioactivity is not known. Therefore, the present study examined the effect of ascorbic acid on .NO bioactivity with isolated rabbit arterial segments. A steady flux of superoxide (1.15 to 2.3 micromol . L-1 . min-1) produced either by pyrogallol autoxidation or a hypoxanthine/xanthine oxidase system inhibited endothelium-derived .NO-mediated arterial relaxation elicited by acetylcholine. This effect of superoxide was completely blocked by SOD (300 IU/mL) and the manganese SOD mimic EUK-8 (300 micromol/L) and partially inhibited by ascorbic acid (10 mmol/L). Lower concentrations of ascorbic acid were ineffective despite scavenging >90% of superoxide. We increased the endogenous flux of superoxide (3.2+/-0.3-fold) by inhibiting vascular copper-zinc SOD with diethyldithiocarbamate. This increased endogenous flux of superoxide produced an impairment of .NO-mediated arterial relaxation that was reversed by EUK-8 (300 micromol/L) but not ascorbic acid (10 mmol/L) despite equivalent scavenging of the endogenous superoxide flux. We used 3-nitrotyrosine formation (from peroxynitrite) as an indicator of .NO interaction with superoxide and found that SOD and EUK-8 compete more effectively with .NO for superoxide than does ascorbic acid. These data indicate that preservation of .NO bioactivity by superoxide scavengers depends not only on superoxide scavenging activity, but also on the rate of superoxide scavenging. Normal extracellular concentrations of ascorbic acid (30 to 150 micromol/L) are not likely to prevent the interaction of .NO with superoxide under physiological conditions.
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PMID:Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. 979 40


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