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)

The addition of 2,3-dichloro-1,4-naphthoquinone (CNQ) to isolated mitochondria supplemented with GSSG resulted in a respiratory burst with the production of O2- and H2O2, and a decrease in the level of measurable disulfide. Superoxide generated by the xanthine oxidase system or by CNQ-treated mitochondria caused the reduction of GSSG to GSH. Both disulfide reductions were partially sensitive to exogeneous SOD. GSSG was also shown to interfere with the epinephrine - adrenochrome superoxide assay system. The findings reported herein support the conclusion that GSSG is capable of scavenging O2- and has the potential to scavenge other free radicals by a similar mechanism.
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PMID:A role for glutathione disulfide as a scavenger of oxygen radicals produced by 2,3-dichloro-1,4-naphthoquinone. 631 84

It has been known that there is remarkable antioxidant activity in the human sera, especially those in inflammation and pregnancy. In the present investigation, various sera were examined for the antioxidant activity with the aid of cultured cells. It was recognized that the serum added to the culture medium protected cells from harmful action of active oxygen generated by a hypoxanthine-xanthine oxidase (HX-XO) system. The inflammatory serum has the greatest protective power, followed by pregnant and normal sera in this order. The antioxidant activity of the serum was inversely related to the Fe concentrations. The addition of ceruloplasmin with SOD action could not inhibit the tissue damage, while addition of catalase or hemoglobin with catalase activity could inhibit it. The protective effect was valid against not only HX-XO, but also H2O2. These results show that the chief active oxygen to cause cell damage is H2O2 and the scavenger antioxidants in the serum are hemoglobin and catalase.
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PMID:Protective effect of the serum against cellular damage by active oxygen in culture. 654 44

In this comprehensive approach, inhibition of autoxidation of PUFA by SOD or other enzymes has been studied. The systems used were: 1) in miscible media in which enzyme, substrat, and peroxidation products are soluble; 2) in non-miscible media such as emulsions; 3) in heterogenous media containing subcellular fragments or whole blended tissue. Depending on experimental conditions, inhibition or activation of peroxidation by SOD can be observed in miscible systems. Other enzymes such as phospholipase A, xanthine oxidase, or horseradish peroxidase are protective in heterogeneous media. Moreover, PUFA hydroperoxide are scavenged by glutathione peroxidase which thus could lessen the autocatalytic effects encountered during peroxidation. Enzymatic inhibition of autoxidation in emulsions was not observed. We conclude that superoxide ion does not play a major role in the initiation of peroxidation and that it may very well act as a free radical chain terminator. In addition, other enzymes such as xanthine oxidase, horseradish peroxidase or phospholipase A show an effective although empirical protection against autoxidation in homogenates of tissues.
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PMID:[Inhibition of the autoxidation of polyunsaturated fatty acids by superoxide dismutase]. 700 94

We established an effective monoepoxide-generating system by combining cytochrome-c (Cyt-c) with a hydrogen peroxide (H2O2)-generating system comprising hypoxanthine (HX), xanthine oxidase (XO) and superoxide dismutase (SOD; HX-XO-SOD-Cyt-c system). Using this and the H2O2-Cyt-c system, we proved that monoepoxide production from linoleic acid was due to hydroxy radical formation by the reaction of Cyt-c with H2O2 and not to the formation of other active oxygen species.
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PMID:Establishment of a monoepoxide (leukotoxin and its isomer) producing system using a hydrogen peroxide-generating system. 748 37

The effect of reducing agents, including N-acetylcysteine (NAC), dithiothreitol (DTT), and 2-mercaptoethanol (2-ME) on nuclear transcription factor-kappa B (NF-kappa B) activation and manganese superoxide dismutase (MnSOD) expression was investigated in a pulmonary adenocarcinoma (A549) cell line. NAC, DTT, and 2-ME each activated the transcription factor NF-kappa B and increased steady-state levels of MnSOD mRNA and enzyme activity in these cells. In addition, NAC, DTT, and 2-ME increased chloramphenicol acetyltransferase (CAT) activity in cells transfected with a construct containing the CAT gene under the control of the rat MnSOD promoter. SOD and catalase (500 U/ml) plus ethanol (1 mM) did not inhibit activation of NF-kappa B or elevation of steady-state MnSOD mRNA levels by NAC, DTT, or 2-ME. Controls in which comparable amounts of O2-. to those produced by thiols were generated by hypoxanthine and xanthine oxidase, or in which H2O2 was added directly, had neither activated NF-kappa B nor elevated MnSOD mRNA. This shows that reactive oxygen intermediates, which may be formed during autooxidation, may not contribute to activation of NF-kappa B. Because the MnSOD promoter also contains potential binding sites for other transcription factors, such as promoter-selective transcription factor-1 (SP-1), activator protein-1 (AP-1), AP-2, adenosine 3',5'-cyclic monophosphate-regulator element binding factor (CREB), and transcription factor IID complex (TFIID), the effect of thiols on their activation also were evaluated. In contrast to findings with NF-kappa B, there was only minor activation of AP-1 by thiols, and none of the other transcription factors were activated by thiols. AP-1 activation was inhibited by catalase (500 U/ml) plus SOD plus ethanol (1 mM). Addition of 700 microM H2O2 also activated AP-1, and catalase at 500 U/ml prevented this activation. This indicates that H2O2 produced as a result of autooxidation of thiols can activate AP-1 but not NF-kappa B. Thus a close association between exposure to reducing agents, activation of NF-kappa B, and elevation of MnSOD gene expression is demonstrated.
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PMID:Activation of NF-kappa B and elevation of MnSOD gene expression by thiol reducing agents in lung adenocarcinoma (A549) cells. 749 77

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

The crystal structure of the aldehyde oxido-reductase (Mop) from the sulfate reducing anaerobic Gram-negative bacterium Desulfovibrio gigas has been determined at 2.25 A resolution by multiple isomorphous replacement and refined. The protein, a homodimer of 907 amino acid residues subunits, is a member of the xanthine oxidase family. The protein contains a molybdopterin cofactor (Mo-co) and two different [2Fe-2S] centers. It is folded into four domains of which the first two bind the iron sulfur centers and the last two are involved in Mo-co binding. Mo-co is a molybdenum molybdopterin cytosine dinucleotide. Molybdopterin forms a tricyclic system with the pterin bicycle annealed to a pyran ring. The molybdopterin dinucleotide is deeply buried in the protein. The cis-dithiolene group of the pyran ring binds the molybdenum, which is coordinated by three more (oxygen) ligands.
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PMID:Crystal structure of the xanthine oxidase-related aldehyde oxido-reductase from D. gigas. 750 41

The aim of this study was to determine the cellular source of oxygen free radicals generated by isolated hepatocytes during post-anoxic reoxygenation. Superoxide anions (O2.-) were detected by lucigenin chemiluminescence. Cell damage was assessed by LDH release. During anoxia, the chemiluminescence decreased to background levels while LDH release increased 8-fold. During reoxygenation, O2.- formation increased 15-fold within 15 min then declined towards control levels. LDH release increased from 161 to 285 mU/min in the first 30 min of reoxygenation, then declined toward the control rate. Allopurinol, an inhibitor of the xanthine-xanthine oxidase system, did not inhibit O2.- formation nor LDH release. Antimycin, a mitochondrial complex III inhibitor that does not block O2.- formation, increased both O2.- generation and LDH release 82 and 133% respectively. Diphenyleneiodonium (DPI), a mitochondrial and microsomal NADPH oxidase inhibitor, reduced O2.- and LDH release 60-70%. SOD, which catalyzes the dismutation of O2.- to H2O2, was without effect on O2.- and LDH release, but TEMPO, a stable nitroxide which mimics SOD and easily penetrates the cell membrane, decreased O2.-86% without affecting LDH. These results suggest that mitochondria or microsomes are the principal sites of O2.- production during reoxygenation of isolated hepatocytes, whereas the cytosolic xanthine/xanthine oxidase system is apparently not involved.
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PMID:Source of oxygen free radicals produced by rat hepatocytes during postanoxic reoxygenation. 754 22

A superoxide dismutase derivative (SM-SOD) that circulates and is bound to albumin with a half-life of 6 h was injected intraperitoneally into rats before exhaustive treadmill running to study its antioxidant scavenging capacity in the plasma and soleus and tibialis muscles. The exercise induced a marked increase in xanthine oxidase activity in plasma and an increase in thiobarbituric acid-reactive substances in the plasma as well as in the soleus and tibialis muscles of nonadministered rats immediately after the exercise. The immunoreactive content and activity of both SOD isoenzymes (Cu,Zn-SOD and Mn-SOD) of the nonadministered rats increased in the soleus and tibialis muscles immediately after running. SM-SOD treatment definitely attenuated the degree of the increase in thiobarbituric acid-reactive substances and xanthine oxidase in all samples examined immediately after exercise. Glutathione peroxidase activity significantly increased in the soleus muscle of nonadministered rats 1 day after running, whereas catalase activity remained unchanged throughout the experimental period. These results suggest that a single bout of exhaustive exercise induces oxidative stress in skeletal muscle of rats and that this oxidative stress can be attenuated by exogenous SM-SOD.
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PMID:Superoxide dismutase derivative reduces oxidative damage in skeletal muscle of rats during exhaustive exercise. 755 9

1. In this study we compared the ability of superoxide anion to destroy the relaxant activity of basal and acetylcholine (ACh)-stimulated activity of NO in isolated rings of rat aorta. 2. Superoxide dismutase (SOD, 1-300 u ml-1) induced a concentration-dependent relaxation of phenylephrine (PE)-induced tone in endothelium-containing rings which was blocked by NG-nitro-L-arginine (L-NOARG, 30 microM), but had no effect on endothelium-denuded rings. It was likely therefore that the relaxant action of SOD resulted from protection of basally produced NO from destruction by superoxide anion, generated either within the tissue or in the oxygenated Krebs solution. 3. In contrast, a concentration of SOD (50 u ml-1) which produced almost maximal enhancement of basal NO activity, had no effect on ACh (10 nM-3 microM)-induced relaxation. 4. In the presence of catalase (3000 u ml-1) to prevent the actions of hydrogen peroxide, superoxide anion generation using hypoxanthine (HX, 0.1 mM)/xanthine oxidase (XO, 16 mu ml-1) produced an augmentation of PE-induced tone in endothelium-containing but not endothelium-denuded rings. This was likely to have resulted from removal of the tonic vasodilator action of basally-produced NO by superoxide anion, since it was blocked in tissues treated with SOD (250 u ml-1), NG-monomethyl-L-arginine (L-NMMA, 30 microM) or L-NOARG (30 microM). Pyrogallol (0.1 mM) had a similar action to HX/XO, but produced an additional augmentation of tone by an endothelium-independent mechanism. 5. In contrast to their ability to destroy almost completely the basal activity of NO, HX (0.1 mM)/XO(16 mu ml-1) and pyrogallol (0.1 mM) had no effect on ACh-induced relaxation at any concentration. An increase in the concentration of HX to 1 mM or pyrogallol to 0.3 mM did, however, lead to a profound decrease in the magnitude and time course of ACh-induced relaxation at all concentrations.6. Treatment with diethyldithiocarbamate (DETCA, 0.1 mM, 1 h) to inhibit endogenous Cu-Zn SOD,augmented PE-induced tone in endothelium-containing rings and abolished the ability of HX (0.1 mM)/XO (16 mu ml-1) and L-NMMA (30 microM) to augment tone. It was likely that DETCA had led to the destruction of basal NO activity by increasing superoxide anion levels since its actions were reversed by exogenous SOD (10-300 upsilon ml-1).7. In contrast to its ability to destroy basal activity of NO completely, DETCA (0.1 mM) produced only a slight blockade of ACh-induced relaxation. However, if these tissues were subsequently treated with concentrations of HX (0.1 mM)/XO (16 mu ml-1) or pyrogallol (0.1 mM), which had no effect by themselves on ACh-induced relaxation, a profound blockade was seen and this was reversed completely with SOD (250 u ml-1).8. The data suggest that basal activity of NO is more sensitive to inactivation by superoxide anion than ACh-stimulated activity and this probably results from differential protection by endogenous Cu-ZnSOD. It is possible therefore that endogenous SOD lowers superoxide anion levels to such an extent that only small amounts of NO, such as those produced under basal conditions, are destroyed. Following generation of superoxide anion with HX/XO or pyrogallol, or inhibition of Cu-Zn SOD with DETCA,levels of the free radical will increase such that greater amounts of NO, such as those produced following stimulation with ACh, will then be destroyed.
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PMID:Differential sensitivity of basal and acetylcholine-stimulated activity of nitric oxide to destruction by superoxide anion in rat aorta. 758 32


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