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)

Cell extracts of Clostridium acidiurici, C. cylindrosporum, and C. purinolyticum converted purine, hypoxanthine, 2-hydroxypurine, 6,8-dihydroxypurine, and uric acid into xanthine by the shortest possible route. Adenine was transformed to xanthine only by C. purinolyticum, whereas the other two species formed 6-amino-8-hydroxypurine, which was neither deaminated nor hydroxylated further. 8-Hydroxypurine was formed from purine by all three species. Xanthine dehydrogenase activity was constitutively expressed by C. purinolyticum. Due to the lability of the enzyme activity, comparative studies could not be done with a purified preparation. All enzymes reported to be involved in formiminoglycine metabolism of C. acidiurici and C. cylindrosporum were present in C. purinolyticum. However, glycine was reduced directly to acetate in all three species, as indicated by radiochemical data and by the detection of glycine reductase in cell extracts of C. cylindrosporum and C. purinolyticum. The expression of glycine reductase and the high ratio of glycine fermented to uric acid present points to an energetic advantage for the glycine reductase system, which is expressed when selenium compounds are added to the growth media.
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PMID:Purine and glycine metabolism by purinolytic clostridia. 683 77

We have developed a quantitative assay to monitor the oxidative burst (H2O2 production) of polymorphonuclear leukocytes (PMNL) using single cell analysis by flow cytometry, and have examined whether PMNL respond to membrane stimulation with an all-or-none oxidative burst. During incubation with normal neutrophils, dichlorofluorescin diacetate diffused into the cells, was hydrolyzed to 2',7'-dichlorofluorescin (DCFH) and was thereby trapped within the cells. The intracellular DCFH, a nonfluorescent fluorescein analogue, was oxidized to highly fluorescent 2',7'-dichlorofluorescein (DCF) by PMNL stimulated by phorbol myristate acetate (PMA). That the oxidative product was DCF was shown by excitation/emission spectra and by mass spectrometry of the product from PMA-stimulated PMNL. Normal resting and PMA-stimulated PMNL oxidized 6.9 +/- 0.7 and 160 +/- 13 attomoles DCF per cell, respectively, in 15 min. Absence of calcium and magnesium ions and/or addition of 2 mM EDTA did not inhibit DCF formation by PMNL stimulated by 100 ng/ml PMA. Since EDTA prevented aggregation of PMNL (even when stimulated by 100 ng/ml PMA), which would prevent accurate flow cytometric analysis, further experiments were performed with EDTA in the medium. A close correlation between average DCFH oxidation and hexose monophosphate shunt stimulation was demonstrated using cells from patients whose PMNL had oxidative metabolic defects of varying severity. Intracellular DCFH was also oxidized by reagent H2O2 or oxygen derivatives generated by glucose oxidase + glucose or by xanthine oxidase + acetaldehyde; DCFH oxidation by these systems was inhibited by catalase but unchanged by superoxide dismutase. The data indicate that the DCFH oxidation assay is quantitatively related to the oxidative metabolic burst of PMNL, and they strongly suggest that the reaction is mediated by H2O2 generated by the PMNL. Incubation of PMNL with varying concentrations of PMA caused graded responses by all PMNL present; i.e., 1 ng/ml PMA caused a mean response of 34% maximal with a single population of responding PMNL (rather than 66% resting and 34% fully stimulated as predicted by the all-or-none hypothesis). Thus, with these assay conditions, oxidative product formation by PMNL occurs as a graded response to membrane stimulation by PMA.
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PMID:Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. 683 55

The activation of N2-methyl-9-hydroxyellipticinium acetate (4) by a peroxidase--H2O2 system leads to the formation of an omicron-quinone (7a). This omicron-quinone is not directly generated from the starting material but through a quinone imine intermediate (6) which is subsequently oxidized. This reaction is highly dependent on pH values. The omicron-quinone 7a is easily protonated (7b), gives an addition product with methanol (9), and is reduced by cysteine. The omicron-quinone 7b has a rather low inhibitory effect against L1210 leukemia cell multiplication but acts as an electron carrier and dramatically augments the oxygen consumption in xanthine oxidase-NADH and rat liver microsomes-NADPH systems.
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PMID:omicron-Quinone formation in the biochemical oxidation of the antitumor drug N2-methyl-9-hydroxyellipticinium acetate. 683 91

Reductive activation of misonidazole and misondiazole acetate, a simple derivative, in the presence of xanthine oxidase causes inactivation of the enzyme. The inactivation is not accompanied by binding of the misonidazole to the enzyme. The nitroreductase activity of xanthine oxidase is inhibited as measured by the reduction of 3,5-dinitrobenzonitrile (DNBN). Cysteine does not appear to protect against the enzyme inactivation by misonidazole but, by itself, cysteine has a strong stimulating effect on the reduction of DNBN. The possible significance of these reactions to the toxicity of misonidazole are discussed.
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PMID:Reductive activation of nitroaromatics and enzyme inhibition: misonidazole and xanthine oxidase. 689 6

We have characterized the effects of phorbol myristate acetate (PMA) on human monocyte and neutrophil oxidative metabolism and antibody-dependent cytotoxicity toward anti-D sensitized human erythrocytes (RBC) and a human lymphoblastoid cell line (CEM). Hexose monophosphate shunt activity was measured by [1-(14)C]glucose oxidation and target lysis by (51)Cr release. PMA produced a dose-dependent stimulation of hexose monophosphate shunt activity. Neutrophils responded with higher hexose monophosphate shunt activity and at a lower PMA concentration than did monocytes. PMA increased monocyte lysis of antibody-sensitized RBC by two-thirds, but did not affect lysis of CEM targets. Neutrophils were unable to lyse either antibody-sensitized or nonsensitized RBC without the addition of PMA. When PMA was added, lysis of both targets increased markedly. Neutrophils without PMA were able to lyse a small number of both antibody-sensitized and nonsensitized CEM targets. PMA also increased neutrophil lysis of these targets. Target lysis by neutrophils from a patient with chronic granulomatous disease, cells unable to produce reactive oxygen species, was not increased by PMA. Chronic granulomatous disease monocytes, however, responded to PMA by more than doubling lysis of antibody-sensitized RBC. Hypoxia inhibited PMA augmentation of antibody-sensitized RBC lysis by neutrophils, but not by monocytes. Generation of reactive oxygen species by the xanthine-xanthine oxidase system inhibited CEM growth, but did not cause lysis, indicating that in some cases oxidative injury may be nonlytic. We suggest that PMA augments neutrophil cytotoxicity to tumor and RBC targets by stimulating reactive oxygen species-mediated lysis, but in monocytes augmentation of lysis is due to activation of a nonoxidative mechanism of lysis.
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PMID:Activation of monocyte and granulocyte antibody-dependent cytotoxicity by phorbol myristate acetate. 706 17

Natural killer cells spontaneously lyse certain tumor cells and may defend against malignancy. We have previously shown that natural killing (NK) by human peripheral blood mononuclear cells (PBMC) is suppressed in vitro by phorbol diester tumor promoters, including 12-O-tetradecanoylphorbol-13-acetate (TPA). We here demonstrate that suppression of NK is mediated by monocytes or polymorphonuclear leukocytes (PMN) and that suppression is dependent on the generation of reactive forms of molecular oxygen (RO), particularly hydrogen peroxide (H2O2). NK was suppressed not only by TPA but also by opsonized zymosan (yeast cell walls), which, like TPA, was not toxic to PBMC. Both TPA and zymosan stimulated the production of superoxide anion (O2-) and H2O2 by PBMC. Production of RO correlated with suppression of NK. When PBMC were depleted of monocytes, the production of RO and the suppression of NK were both markedly reduced. Suppression could be restored by monocytes or PMN, both of which produced RO in response to TPA or zymosan. Suppression of NK was dependent on RO. Monocytes or PMN from a patient with chronic granulomatous disease, whose cells cannot generate RO, did not mediate suppression of NK. Suppression was also reduced in glucose-free medium, which did not support the generation of RO. Suppression of NK by TPA was inhibited by catalase. Bovine superoxide dismutase had a limited effect on suppression, even in high concentration, and tyrosine-copper (II) complex, which also enhances dismutation of O2- to H2O2, had almost no effect on suppression. When H2O2 was directly generated enzymatically from glucose oxidase and glucose, NK was suppressed and suppression was reversed by catalase. NK was also suppressed by the enzymatic generation of O2- from xanthine oxidase and xanthine, but suppression under these conditions was again inhibited by catalase and not by superoxide dismutase, indicating that suppression was due to the secondary formation of H2O2 from O2-. These results indicate that H2O2 is important in suppression of NK. Myeloperoxidase did not appear to play a role in suppression because inhibition of this enzyme by sodium azide, cyanide, or aminotriazole did not prevent suppression of NK. Suppression of NK was reversible; after exposure to zymosan, NK could be partially restored by the addition of catalase and superoxide dismutase or by the removal of zymosan. These studies demonstrate cellular regulation of NK by monocytes or polymorphonuclear leukocytes and indicate a role for RO in immunoregulation.
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PMID:Suppression of natural killing in vitro by monocytes and polymorphonuclear leukocytes: requirement for reactive metabolites of oxygen. 707 51

Recent studies have demonstrated that nitric oxide (NO) in the presence of superoxide (O2-) may mediate mutagenesis via the N-nitrosation of DNA bases followed by nitrosative deamination to yield their hydroxylated derivatives. We have found that phorbol myristate acetate (PMA)-activated extravasated rat neutrophils (PMNs) will N-nitrosate 2,3-diaminonaphthalene (DAN) to yield its highly fluorescent nitrosation product 2,3-naphthotriazole (triazole) via the L-arginine dependent formation of NO. Addition of SOD enhanced triazole formation suggesting that O2- production may inhibit the N-nitrosating activity and thus the mutagenic activity of inflammatory PMNs. The objective of this study was to assess the role of superoxide as a modulator of NO-dependent N-nitrosation reactions using PMA-activated PMNs as well as a chemically defined-system that generates both NO and superoxide. We found that PMA-activation of PMNs reduced found that PMA-activation of PMNs reduced the amount of N-nitrosation of DAN by approximately 64% when compared to non-stimulated cells (450 vs. 1250 nM). Addition of SOD but not inactivated SOD or catalase to PMA-activated PMNs enhanced the formation of triazole by approximately 4-fold (1950 nM). In addition, we found that the NO-releasing spermine/NO adduct (Sp/NO; 50 microM) which produces approximately 1.0 nmol NO/min generated approximately 8000 nM of triazole whereas the combination of Sp/NO and a superoxide generator (hypoxanthine/xanthine oxidase) that produces approximately 1.0 nmol O2-/min reduced triazole formation by 90% (790 nM). Addition of SOD but not catalase restored the N-nitrosating activity. We conclude that equimolar fluxes of superoxide react rapidly with NO to generate products that have only limited ability to N-nitrosate aromatic amino compounds and thus may have limited ability to promote mutagenesis via the nitrosative deamination of DNA bases.
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PMID:Effects of superoxide on nitric oxide-dependent N-nitrosation reactions. 749 44

We compared the effects of phorbol 12-myristate 13-acetate (PMA) and thrombin with those of nonlytic concentrations of reactive oxygen species (ROS) generated by hypoxanthine (HX)-xanthine oxidase (XO) on the adhesion properties of human umbilical cord vein endothelial cells (HUVEC) to resting polymorphonuclear neutrophils (PMN). PMN adherence to HX-XO-treated HUVEC was increased approximately twofold to 2.5-fold relative to untreated HUVEC, both immediately and after 2 hours. It was not additive to that induced by PMA or thrombin stimulation of HUVEC. ROS-induced adherence was not due to platelet-activating factor (PAF) or P-selectin expression, as it was neither antagonized by BN52021 (PAF receptor antagonist) nor inhibited by anti-P-selectin monoclonal antibody (MoAb), contrary to the increased adhesion of PMA- and thrombin-stimulated HUVEC. PMN preincubated with mannose-6-P or N-acetylneuraminic acid (sialic acid), but not mannose or galactose-6-P, showed reduced adherence to ROS-treated HUVEC, suggesting that carbohydrate molecules were expressed on the latter and served as the ligand for the PMN L-selectin. Intercellular adhesion molecule (ICAM-1), constitutively present on the surface of resting HUVEC, was involved in the PMN adherence to ROS-treated HUVEC, since this adherence was inhibited by anti-ICAM-1, anti-CD11a, anti-CD11b, and anti-CD18 MoAbs. A non-CD18, non-ICAM-1-dependent mechanism is also involved in this adherence, since effects of these MoAbs were not additive; moreover, combinations of anti-CD18 and anti-ICAM-1 MoAbs with mannose-6-P and sialic acid completely inhibited PMN adherence. The increased binding of PMN to HX-XO-exposed HUVEC observed here involved IC-AM-1, but was independent of its upregulation, and another non-ICAM-1-dependent mechanism, in which carbohydrates expressed on HUVEC recognize L-selectin on PMN.
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PMID:Reactive oxygen species rapidly increase endothelial ICAM-1 ability to bind neutrophils without detectable upregulation. 751 10

The reaction kinetics of radioadaptive response of low doses of X-rays have been studied in quiescent cultured mouse cells. Mouse m5S cells pre-exposed in G1 to low doses of X-rays became insensitive to the induction of chromosome aberrations, mutation toward 6-thioguanine resistance, and cell killing. Adapted cells were, however, more susceptible to morphological transformation by subsequent high challenging doses of X-rays. The cytogenetic adaptation, which lasted about 20 h pertained to a narrow dose range. X-ray doses below and above 0.1 Gy appeared to be recognized as different signals; higher doses of X-rays were incapable of inducing adaptation and rapidly extinguished the adapted condition. Treatment with 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and hydrogen peroxide, but not the xanthine/xanthine oxidase superoxide-generating system, mimicked X-rays in inducing adaptation when applied at low doses. Over-exposure to TPA or inhibitors of protein kinase C (PKC) abrogated the adaptive response to X-rays, providing evidence for the involvement of a PKC-mediated signalling pathway. The lack of radioadaptive response in a tumorigenic variant, clone 6110, and its restoration in the morphological revertant obtained by introducing human chromosome 11 further suggested that interference of signalling pathways may alter radioadaptive responses in malignant cells.
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PMID:On the reaction kinetics of the radioadaptive response in cultured mouse cells. 756 88

Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid), a novel antiulcer agent, has been reported to prevent various acute experimental gastric mucosal lesions and to accelerate the healing of chronic gastric ulcers. We investigated the effect of rebamipide on rat gastric mucosa damaged by exposure to 30 min of ischemia and 60 min of reperfusion (I/R) with continuous intragastric instillation of 0.1 N HCl (1 ml/100 g body weight) into the stomach. Rebamipide, at 30 and 100 mg/kg, i.p., reduced the mucosal damage score from 2.28 (I/R vehicle group) to 1.54 and 1.07, respectively. Pretreatment with rebamipide significantly reduced the activity of myeloperoxidase (an index of neutrophil infiltration) and preserved the activities of superoxide dismutase and nitric oxide synthase in the gastric mucosa with inhibition of malondialdehyde production. Thus, a negative correlation between the activities of nitric oxide synthase and myeloperoxidase (y = 4.35-9.45x, r = .67, P < .01) was observed. In an in vitro study, rebamipide inhibited N-formyl-met-leu-phe-induced chemotaxis of neutrophils and production of superoxide anion from opsonized zymosan-stimulated neutrophils. However, it did not affect the production of superoxide anion either by the xanthine-xanthine oxidase reaction or phorbol 12-myristate 13-acetate-stimulated neutrophils. Based on these results, it is suggested that rebamipide exerts a protective effect on the I/R-induced gastric mucosal damage through inhibition of mobilization and activation of neutrophils in association with an attenuation of the decreases in both superoxide dismutase and nitric oxide synthase activities, thereby preventing the gastric microcirculation from deterioration.
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PMID:Preventive effect of rebamipide on gastric lesions induced by ischemia-reperfusion in the rat. 756 69


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