Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asbestos resembles the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), in its ability to elicit release of superoxide (O2-.) from rodent alveolar macrophages (AM) in vitro. In addition, superoxide dismutase (SOD), the antioxidant enzyme scavenging O2-, is increased in cultures of tracheobronchial epithelial cells and lung fibroblasts after exposure to either crocidolite or chrysotile asbestos. Our objectives here were to determine: (1) the chemical and physical properties of asbestos important in the generation of O2- from rat AM; and (2) the effects of O2- in comparison with asbestos on biosyntheses of collagen and non-collagen protein in rat lung fibroblasts in vitro. We were also interested in whether increased production of SOD occurred in the lungs of rats after inhalation of crocidolite asbestos. To determine whether O2- was elicited in response to a variety of asbestiform fibres, AM lavaged from Fischer 344 rat lungs were exposed in vitro to equivalent non-toxic amounts of crocidolite asbestos, erionite, Code 100 fibreglass, sepiolite, and their non-fibrous analogues, riebeckite, mordenite and glass particles. In addition, sized preparations of long (greater than 10 microns) and short (less than 2 microns) asbestos were introduced at identical concentrations to determine whether length of fibres is critical in O2- release. The amount of O2- released from AM in response to dusts was then determined by measuring SOD-inhibitable reduction of cytochrome C. All asbestiform fibres caused a significant (p less than 0.05) increase in generation of O2- from epithelial cells, whereas non-fibrous particles were less active at comparable concentrations. Experiments with long (greater than 10 microns) versus short (less than 2 microns) chrysotile showed that long fibres caused a more striking, dosage-dependent release of O2-. To determine whether O2- plays a role in the causation of fibrotic lung disease, rat lung fibroblasts were exposed to a biochemical generation system (xanthine-xanthine oxidase) for O2- before quantitation of cell-associated collagen and non-collagen protein at 24, 48 and 72 h thereafter. At the latter time periods, significant increases in total collagen per ng DNA were observed. In comparison with controls, the generation system for O2- also caused an initial decrease in synthesis of non-collagen protein followed by increases in synthesis of non-collagen protein at 48 and 72 h.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of fibre-induced superoxide release from alveolar macrophages and induction of superoxide dismutase in the lungs of rats inhaling crocidolite. 254 20

Rates of enzymatic single-electron reduction of some myotoxic quinones to semiquinone metabolites in an in vitro xanthine oxidase/hypoxanthine/catalase system varied widely. Naphthoquinones, especially juglone, were found to undergo rapid single-electron reduction. Benzoquinones and benzoquinoneimines, as well as phenanthrene-9,10-quinone, benzo[a]pyrene-3,6-quinone, and diethylstilbestrolquinone, were also actively reduced. The anthraquinones danthron, doxorubicin and emodin were poorly metabolized in this system. N-Acetylcysteine inhibited quinone-stimulated cytochrome C reduction at high concentrations. The results of this study are discussed with respect to cytotoxicity and mutagenicity of selected quinones.
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PMID:Relative metabolism of quinones to semiquinone radicals in xanthine oxidase system. 255 68

The ability of Oxyphenbutazone (a non-steroidal antiinflammatory drug) to react with singlet oxygen and superoxide anions, possible mediators of the damage to the lipids of the cell membranes during inflammation was studied. Oxyphenbutazone inhibited the reduction of nitroblue tetrazolium in aerobic riboflavin-photosensitized oxidation of methionine, but did not influence the cytochrome C-reduction by superoxide-generating system xanthine-xanthine oxidase. Oxyphenbutazone was photooxidized in the presence of Rose Bengal, the latter being a photosensitizer. The increase of the reaction rate of Oxyphenbutazone-oxidation in D2O as compared to H2O, as well as the inhibition of oxidation by singlet oxygen-quencher sodium azide confirmed the participation of singlet oxygen in this process. It was found that Oxyphenbutazone reacted with singlet oxygen, but did not react with superoxide anions. This was supported by the observed protection of erythrocyte membranes from the hemolytic action of the singlet oxygen-generating system Rose Bengal + light.
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PMID:Reactions of oxyphenbutazone with active oxygen species. 282 29

Cytochrome a1c1 (nitrite-cytochrome c oxidoreductase) purified from Nitrobacter winogradskyi (formerly N. agilis) contained molybdenum, non-heme iron, and acid-labile sulfur in addition to hemes a and c; it contained 1 mol of heme a, 4-5 g atoms of non-heme iron, 2-5 g atoms of acid-labile sulfur, and 1-2 g atoms of molybdenum per mol of heme c, but did not contain copper. The fluorescence spectra of the molybdenum cofactor derivative prepared from cytochrome a1c1 were very similar to those of the cofactor derivative from xanthine oxidase, and the aponitrate reductase of nit-1 mutant of Neurospora crassa was complemented by addition of the molybdenum cofactor derived from the cytochrome. Further, the ESR spectrum of cytochrome a1c1 was similar to that of liver sulfite oxidase. The content of cytochrome a1 in the cells cultivated with the medium in which tungsten was substituted for molybdenum markedly decreased as compared with that in the cells cultivated in the molybdenum-supplemented medium. These results indicate that cytochrome a1c1 is an iron-sulfur molybdoenzyme which contains hemes a and c.
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PMID:Nitrobacter winogradskyi cytochrome a1c1 is an iron-sulfur molybdoenzyme having hemes a and c. 282 43

Heme-nonapeptide inhibits NADH and NADPH dependent lipid peroxidation of brain microsomes in the presence or absence of ADP-Fe complex. The transient accumulation of lipid peroxides during NADH or NADPH dependent, ADP-Fe stimulated lipid peroxidation, is inhibited by heme-nonapeptide. Oxygen consumption of brain microsomes in the presence of NADH or NADPH is stimulated by heme-nonapeptide. Reduction of cytochrome-c and nitro-tetrazolium-blue by O2- generated by xanthine oxidase is inhibited by heme-nonapeptide.
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PMID:Effect of a heme-peptide derived from cytochrome-c on lipid peroxidation. I. Effects on brain microsomes. 302 27

Standard microelectrode techniques were used to study the effects of a free radical generating system on action potentials recorded from guinea pig ventricular myocardium. Free radicals were generated by mixing xanthine oxidase (0.02-0.04 mu/ml) with the superfusate-modified Locke's solution containing purine 2.3 mM. The system was validated by demonstrating that it could reduce cytochrome C at a rate of 15.9 +/- 1.5 mol/l/min. This rate was decreased to 3.0 +/- 0.3 (p less than 0.001) in the presence of superoxide dismutase (12 mg/100 ml), and the reaction was absent if xanthine oxidase and purine were premixed for 60 minutes prior to adding cytochrome C. Superfusion of guinea pig ventricular strips with the free radical generating system (20-30 minutes) resulted in a highly significant reduction in resting potential from -79.3 +/- 1.8 mV to -70.9 +/- 1.4 mV (p less than 0.0001, n = 6) and in action potential amplitude from 110.9 +/- 2.2 mV to 101.7 +/- 4.0 mV (p less than 0.0001). There was an accompanying fall in maximum rate of depolarization (Vmax) from 254.1 +/- 17.7 V/sec to 207.1 +/- 18.6 V/sec (p less than 0.01) and no significant change in action potential duration. These changes were accompanied by spontaneous activity in 3 of 6 preparations and reversed after 20-30 minutes washing in Locke's solution. They were largely abolished by adding superoxide dismutase (12 mg/100 ml) to the superfusate and completely absent if the xanthine oxidase and purine were premixed for 60 minutes before superfusing the myocardium. We conclude that the phenomena observed may contribute to the genesis of reperfusion arrhythmias.
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PMID:Proarrhythmic effects of an oxygen-derived free radical generating system on action potentials recorded from guinea pig ventricular myocardium: a possible cause of reperfusion-induced arrhythmias. 303 67

An automated enzymatic method is described for the determination of Cu,Zn-superoxide dismutase (SOD) in plasma or erythrocytes using the xanthine-xanthine oxidase and cytochrome C coupled assay. This method was adapted to an Abbott ABA-200 discrete analyzer. Coefficients of variation for within-run and day-to-day analyses were less than 5%. Only 2.5 muL of serum or erythrocyte extract is required so a capillary tube sample of blood (70 muL) is sufficient for the assay. Recovery of added SOD ranged from 92 to 101%. The method reported here is practical for use in a clinical chemistry laboratory for monitoring changes in this enzyme, which is a sensitive early indicator of alterations in copper status.
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PMID:An automated method for the determination of Cu,Zn-superoxide dismutase in plasma and erythrocytes using an ABA-200 discrete analyzer. 308 43

Following therapeutic administration, cyclophosphamide and Adriamycin are biotransformed to reactive metabolites, some of which are responsible for undesirable systemic toxicities of these chemicals, whereas others are responsible for their chemotherapeutic effectiveness. Microsomal mixed function oxidases activate cyclophosphamide to produce phosphoramide mustard and acrolein, while cytochrome reductase and xanthine oxidase are capable of transforming Adriamycin and forming free radicals. These reactive metabolites produce unwanted toxic side effects; however, their action may be partially ameliorated by the concomitant administration of thiols. In this study we evaluated the therapeutic activity of combinations of mesna (2-mercaptoethanesulfonate) with cyclophosphamide or Adriamycin in mice with a variety of transplantable tumors (L1210 and P-388 leukemia, Lewis lung and colon 26 carcinoma, B16 melanoma, and M5076 sarcoma). In all cases the administration of mesna prior to cyclophosphamide or Adriamycin treatment did not reduce the antitumor effectiveness of these agents and in some instances (C57BL/6 mice with B16 melanoma or M5076 sarcoma) small improvements were observed. Therefore, the addition of thiols, to reduce effectively the buildup of toxic metabolites of cyclophosphamide or Adriamycin may result in the improved therapeutic effectiveness for these agents in the treatment of cancer.
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PMID:Combinations of mesna with cyclophosphamide or adriamycin in the treatment of mice with tumors. 310 25

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

The relationship between the structure and function of ferricytochrome c bound to the phosphoprotein phosvitin was investigated. The rates of reduction of phosvitin-bound ferricytochrome c by cytochrome b2, ascorbate and the superoxide radical generated by xanthine oxidase wer repressed where the binding ratio was less than half the maximum, but at higher ratios they were restored gradually with increase in the ratio. The affinity of cytochrome b2 for cytochrome c was not affected by binding of cytochrome c to phosvitin. The redox potential of the bond form was lower than that of the free form and only decreased with decrease in the ratio. The conformatin around the heme moiety and the electronic structure of the heme group of bound ferricytochrome c were similar to those of free ferricytochrome c, but the conformational stability in the vicinity of the prosthetic group was related to the binding ratio as ratios above half the maximum and was well correlated with the reduction rate. Since the binding of cytochrome c to phosvitin is much stronger at binding ratios below half the maximum, these results suggest that this binding strength exclusively affects the conformational flexibility of the heme crevice in the cytochrome molecule, thus altering the reduction rate.
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PMID:Relation of the structure and function of ferricytochrome c bound to the phosphoprotein phosvitin. 625 2


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