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)

Widespread environmental pollution with mutagenic and carcinogenic nitrofluorenes contributes to human health risks. Since nitroreduction leads to activation of many nitro compounds, nitroreduction of the nitrofluorene (NF) derivatives by one- and two-electron reductants was examined. Rates of nitroreduction catalyzed by xanthine oxidase (XO)/hypoxanthine and measured via stimulation of acetylated cytochrome c reduction increased with the number of nitro groups and oxidation at C-9: 9-oxo-2,4,7-triNF > 9-oxo-2,7-diNF > 2,7-diNF > 9-oxo-2-NF = 2,5-diNF > 9-hydroxy-2-NF > 2-NF. Ascorbate catalyzed one-electron reduction to nitro anion radicals which reacted with molecular O2 to yield superoxide. Rates of O2 uptake with 9-oxo-2,4,7-triNF and 9-oxo-2,7-diNF were 63 and 0.17 times those, respectively, with equivalent concentrations of nitrofurazone, a classical substrate. Superoxide formation was indicated by the approximately 75% regeneration of O2 upon addition of superoxide dismutase and catalase. 9-Oxo-2,4,7-triNF stimulated O2 uptake in the presence of XO/NADH with typical Michaelis-Menten kinetics with an apparent Km of 0.476 +/- 0.054 microM versus a Km of 6.18 +/- 0.719 microM for nitrofurazone. HPLC analyses of products from reduction catalyzed by XO or diaphorase of Clostridium with NADH showed the following trends for the rates of amine formation from 9-oxo-2,7-diNF > 2,7-diNF; 9-oxo-2-NF > 9-hydroxy-2-NF > 2-NF; 2,7-diNF > 2-NF; and 9-oxo-2,7-diNF > 9-oxo-2-NF. Little or no amine was formed in 95% O2, suggesting O2-labile intermediates. The data herein suggest that oxidation at C-9 and multiple nitro groups increase the potential for nitroreduction of the nitrofluorenes in vivo which may lead to genotoxic effects.
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PMID:Nitroreduction of nitrated and C-9 oxidized fluorenes in vitro. 981 98

1. In this study we investigated the ability of ascorbate to protect nitric oxide from destruction by superoxide anion. 2. Ascorbate produced concentration-dependent relaxation of rings of rat aorta, comprising two components: the first, seen at 1-300 microM, reached a maximum of 45.3+/-2.8%, and was abolished by endothelial removal or treatment with L-NAME (100 microM), demonstrating involvement of nitric oxide. The second occurred at concentrations of 1 mM and above and was associated with falls in the pH of the bathing fluid. 3. Pretreatment with ascorbate at concentrations up to 3 mM had no effect on the relaxation to acetylcholine (10 nM-10 microM) on endothelium-containing rings or adenosine (0.1 microM-3 mM) on endothelium-denuded rings. 4. An oxidant stress was applied to aortic rings, comprising inhibition of endogenous Cu/Zn superoxide dismutase by diethyldithiocarbamate (0.1 mM) followed by generation of superoxide anion by hypoxanthine (0.1 mM/xanthine oxidase (16 u ml(-1)). This reduced maximal acetylcholine-induced relaxation from 96.7+/-1.3% to 42.4+/-3.5% (P<0.001). Treatment with ascorbate (30 microM-3 mM) reversed this blockade in a concentration-dependent manner. 5. Our findings show that ascorbate has the ability to protect nitric oxide from destruction by superoxide anion. This action is seen with ascorbate at levels normally present in plasma, suggesting that this antioxidant may exert a tonic protective effect on nitric oxide within the vasculature.
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PMID:Recovery by ascorbate of impaired nitric oxide-dependent relaxation resulting from oxidant stress in rat aorta. 983 15

Delphinidine-3-(p-coumaroylrutinoside)-5-glucoside (nasunin), an anthocyanin was isolated as purple colored crystals from eggplant peels, Solanum melongena L. 'Chouja'. Using an electron spin resonance spectrometer and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), spin trapping, hydroxyl (.OH) or superoxide anion radicals (02*-) generated by the Fenton reaction or the hypoxanthine-xanthine oxidase system were measured as DMPO-OH or DMPO-OOH spin adducts. L-Ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetra-methyl-2-(4,8,12-trimethyltridecyl)-2 H-1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1) and bovine erythrocyte superoxide dismutase (SOD) were used as standards for .OH and O2*-, respectively. Nasunin directly scavenged O2*- with a potency of 143+/-8 SOD-equivalent units/mg), and inhibited formation of DMPO-OH (0.65+/-0.07 EPC-K1 micromol/mg). A spectrophotometric study showed that nasunin formed an iron complex with a molar ratio of nasunin : Fe3+ of 2 : 1. Therefore, hydroxyl radical scavenging by nasunin is not due to direct radical scavenging but inhibition of .OH generation by chelating iron. Nasunin (1 microM) significantly protected against lipid peroxidation of brain homogenates (p<0.001) as measured by malonaldehyde and 4-hydroxyalkenals. These findings demonstrate that nasunin is a potent O2*- scavenger and iron chelator which can protect against lipid peroxidation.
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PMID:Antioxidant activity of nasunin, an anthocyanin in eggplant. 1010 May 9

The prooxidant/antioxidant imbalance in familial adenomatous polyposis (FAP) is suggested by (i) the intimate connection between APC and prostaglandin H synthase-2 genes, (ii) the increase of the free radical-generating enzyme xanthine oxidase, and (iii) the decrease of antioxidant defences. In this research work we evaluated lipid peroxidation measuring the thiobarbituric acid (TBA) reactive products and we studied the activities of superoxide dismutase (SOD) and catalase as well as the levels of ascorbate and tocopherols in the peripheral blood cells from a total of 27 FAP patients and 83 normal controls. TBA-reactive products were determined according to a previously published method. SOD and catalase activities were determined by the spectrophotometric monitoring of the inhibition of pyrogallol autoxidation and the hydrogen peroxide decomposition rate, respectively. Ascorbate levels were determined by a modified 2,4-dinitrophenylhydrazine method and tocopherol levels by a modified Emmerie-Engle method. The levels of TBA-reactive products were higher in FAP patients than in normal controls. Although no statistically significant differences in SOD and catalase activities were observed between FAP patients and normal controls, we found that ascorbate and tocopherol levels were significantly lower in FAP patients than in normal controls, as assessed by the Mann-Whitney test. Hence, this finding of an imbalance in the prooxidant/antioxidant status may contribute towards new strategies for prevention and therapy in FAP patients.
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PMID:Oxidative stress in familial adenomatous polyposis. 1049 5

The influence of hypoxanthine (HX)/xanthine oxidase (XO) on short-term [electrical field stimulation (EFS; 4 Hz) for 10 s and 3 min; bolus of exogenous NO (10(-5) M)] and long-term [EFS (4 Hz) and continuous NO-infusion for 20 min] nitrergic relaxations was investigated in circular muscle strips of the pig gastric fundus. HX (3x10(-4) M) / XO (64 mu ml(-1)) did not affect EFS for 10 s and 3 min; the short-lasting relaxation in response to a bolus of exogenous NO (10(-5) M) was changed into a biphasic relaxation with a small and short first phase followed by a larger and prolonged second phase. Cu/Zn superoxide dismutase (Cu/Zn SOD; 1000 u ml(-1)) and uricase (100 mu ml(-1)) respectively enhanced the amplitude of the first phase and diminished the amplitude of the second phase. Ascorbate (5x10(-4) M) and bilirubin (2x10(-4) M) prevented the prolonged component. Exposure to HX/XO during long-term EFS elicited a complete, stable reversal of relaxation starting after a delay. During continuous NO-infusion, HX/XO induced an immediate, complete but transient reversal. The antioxidants bilirubin, ascorbate, alpha-tocopherol, urate, glutathione and Cu/Zn SOD, the hydrogen peroxide degrading enzyme catalase, the hydroxyl radical scavengers dimethylsulphoxide and mannitol, and the cofactor flavin adenine dinucleotide did not influence the reversal induced by HX/XO during either EFS or NO-infusion. The cell-permeable manganese SOD mimetic EUK-8 modified the stable reversal during long-term EFS into a transient one. The results suggest that a nitrated uric acid derivative is responsible for the prolonged second phase in the relaxation to a bolus of exogenous NO in the presence of HX/XO. The exact underlying mechanism of the reversal induced by HX/XO during sustained relaxation remains unclear.
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PMID:Interaction of hypoxanthine/xanthine oxidase with nitrergic relaxation in the porcine gastric fundus. 1080 74

The free radical scavenging activities and inhibitory effect of lipid peroxidation of a delphinidin derivative in eggplant were investigated. Delphinidin-3-(p-coumaroylrutinoside)-5-glucoside (nasunin), an anthocyanin, was isolated as purple colored crystals from eggplant peels. Using electron spin resonance spectrometry and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), hydroxyl radicals (OH) or superoxide anion radicals (O(2)(-)) generated by the Fenton reaction or the hypoxanthine-xanthine oxidase system were measured as DMPO-OH or DMPO-OOH spin adducts. L-Ascorbic acid 2-[3, 4-dihydro-2,5,7,8-tetramethyl-2-(4,8, 12-trimethyltridecyl)-2H-1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1) and bovine erythrocyte superoxide dismutase (SOD) were used as standards for OH and O(2)(-) scavengers, respectively. Nasunin showed potent O(2)(-) scavenging (143+/-8 SOD-equivalent U/mg) and OH scavenging (0. 65+/-0.07 EPC-K1-equivalent micromol/mg) activities. Then, by changing the concentration of DMPO to vary the trapping rate of OH, the presence of a competitive reaction between nasunin and OH was studied. The 50% inhibition dose (ID(50)) obtained from the inhibition curve did not change, indicating OH scavenging of nasunin is not due to direct scavenging but inhibition of OH generating system by chelating ferrous ion. Nasunin protection against H(2)O(2)-induced lipid peroxidation in rat brain homogenate was measured at 586 nm using the indicator of malonaldehyde and 4-hydroxyalkenals. Nasunin (<50 microM) protected against lipid peroxidation of brain homogenates. The findings suggest that nasunin is a potent O(2)(-) scavenger and has protective activity against lipid peroxidation.
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PMID:Antioxidant activity of nasunin, an anthocyanin in eggplant peels. 1096 30

The antioxidant activities of two freeze-dried tomato powders as additives for food fortification and stabilization were studied. The two tomato powders were obtained from the whole fruit and from the pulp after "serum" separation, respectively. The antioxidant activity was studied by measuring (a) the inhibition of the singlet oxygen-catalyzed oxidation of alpha-linolenic acid, in the presence or absence of copper ions, as a model of the oxidative processes occurring in foods, and (b) the inhibition of xanthine oxidase (XOD)- and myeloperoxidase (MPO)-catalyzed reactions and copper-induced lipid peroxidation. The partial separation of "serum" decreased the freeze-drying time by 50%. The partially fractionated tomato powder had a 60% lower phenolic content and an 11-fold higher lycopene content than the whole tomato powder, on a dry weight basis. Ascorbic acid was almost completely removed by fractionation. Both the powder obtained from the whole tomato and that obtained from the partially fractionated tomato had antioxidant activity in all the model systems used. Based on these results, we conclude that tomato powders have multifunctional properties, which could address the prevention of oxidative degradations both in foods and in vivo. Therefore, tomato can be regarded as source of food additives for fortification and stabilization, even if it is submitted to technological processes that can cause the loss of the more labile hydrophilic antioxidants.
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PMID:Properties of tomato powders as additives for food fortification and stabilization. 1130 64

Lipopolysaccharide endotoxin and interferon-gamma induced inducible nitric oxide synthase (iNOS) protein expression and nitrite/nitrate formation in microvascular endothelial cell cultures (ECs) derived from rat skeletal muscle. Pretreatment of ECs with ascorbate accumulated a large amount of ascorbate inside the cells and consequently decreased both intracellular oxidant level and iNOS induction. These effects of ascorbate were abolished in the presence of exogenous superoxide generated by xanthine oxidase/xanthine plus catalase but were not altered when N-nitro-L-arginine methyl ester was applied to inhibit nitric oxide synthesis. Ascorbate also attenuated the activation of transcription factor IRF-1 but not NF kappa B. These results indicate that ascorbate inhibits iNOS expression in ECs by an antioxidant mechanism independent of both NF kappa B activation and the reported negative feedback effect of nitric oxide.
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PMID:Ascorbate inhibits iNOS expression in endotoxin- and IFN gamma-stimulated rat skeletal muscle endothelial cells. 1204 83

We previously found that human chymase cleaves big endothelins (ETs) at the Tyr(31)-Gly(32) bond and produces 31-amino acid ETs (1-31), without any further degradation products. In the present study, we investigated the effects of various antioxidants on the ET-1 (1-31)-induced change in intracellular signaling and proliferation of cultured rat aortic smooth muscle cells (RASMC). ET-1 (1-31) stimulated rapid and significant activation of the mitogen-activated protein (MAP) kinase family, i.e. extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK, in RASMC to an extent similar to that of ET-1. All of the antioxidants examined, i.e. N-acetyl-L-cysteine (NAC), diphenyleneiodonium chloride (DPI), and L-(+)-ascorbic acid (ascorbic acid), inhibited both ET-1 (1-31)- and ET-1-induced JNK and p38 MAPK activation but not ERK1/2 activation. Electron paramagnetic resonance (EPR) spectroscopy measurements revealed that NAC, DPI, and ascorbic acid inhibited xanthine oxidase-induced superoxide (O(2)(.-)) generation in a cell-free system. ET-1 (1-31) in addition to ET-1 increased the generation of cellular reactive oxygen species (ROS) in RASMC. ET-1 (1-31)- and ET-1-induced cellular ROS generation was inhibited similarly by NAC, DPI, and ascorbic acid in RASMC. Gel-mobility shift analysis showed that ET-1 (1-31) and ET-1 caused an increase in activator protein-1 (AP-1)-DNA binding activity in RASMC that was inhibited by the above three antioxidants. ET-1 (1-31) increased [3H]thymidine incorporation into cells to an extent similar to that of ET-1. This ET-1 (1-31)-induced increase in [3H]thymidine incorporation was also inhibited by NAC and DPI, but not by ascorbic acid. These results suggest that antioxidants inhibit ET-1 (1-31)-induced RASMC proliferation by inhibiting ROS generation within the cells. The underlying mechanisms of the inhibition of cellular proliferation by antioxidants may be explained, in part, by the inhibition of JNK activation and the resultant inhibition of AP-1-DNA binding.
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PMID:Antioxidants inhibit endothelin-1 (1-31)-induced proliferation of vascular smooth muscle cells via the inhibition of mitogen-activated protein (MAP) kinase and activator protein-1 (AP-1). 1241 65

Much attention has been paid in initial biochemical studies on the ability of indoleamine 2,3-dioxygenase to use superoxide as substrate to cleave tryptophan to N-formyl kynurenine. This ability, however, is limited to the ferric form of the enzyme only, whereas the ferrous form requires oxygen rather than superoxide as substrate. As long as the enzyme is held in the ferrous form, high yield formation of product proceeds from the ferrous oxygen tryptophan ternary complex without the participation of superoxide. Enzyme assays in homogenates are carried out in presence of Methylene Blue, ascorbate and catalase. Ascorbate can be replaced by other reductants like e.g. tetrahydrobiopterin. Experiments with alteration of intracellular tetrahydrobiopterin concentrations in intact interferon-gamma treated cells clearly showed that tetrahydrobiopterin is not required for the indoleamine 2,3-dioxygenase reaction. In homogenates of interferon-gamma treated T-24 cells, substrates of xanthine oxidase did not stimulate the indoleamine 2,3-dioxygenase reaction, nor did allopurinol inhibit the reaction, nor did superoxide dismutase alter indoleamine 2,3-dioxygenase activity irrespective of the reductant used. From these experiments we concluded that molecular oxygen rather than superoxide is used in cell homogenates by indoleamine 2,3-dioxygenase to cleave L-tryptophan. A detailed analysis of available reports on oxygen and superoxide utilization by indoleamine 2,3-dioxygenase gives a comprehensive picture that the enzyme uses oxygen bound to the ferrous enzyme for cleavage of tryptophan, that the enzyme needs to be held by reductants in the ferrous state in enzyme incubations, and that superoxide is one of the reductants capable performing this reduction.
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PMID:Substrate and cofactor requirements of indoleamine 2,3-dioxygenase in interferon-gamma-treated cells: utilization of oxygen rather than superoxide. 1743 Jan 7


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