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)

Eimeria bovis and Toxoplasma gondii differ in their susceptibility to macrophages activated by lymphokines. Interferon-gamma can activate macrophages to totally inhibit E. bovis sporozoite development, whereas growth of T. gondii tachyzoites in macrophages is not totally affected. The susceptibility of these parasites to oxygen intermediates and their ability to evade the oxidative burst by macrophages were investigated in cell-free systems. Using a logistic model to assess growth inhibition, T. gondii growth was impaired by 50% at 10(-4.25) M (56 microM) H2O2, with 30 min as the optimum time for measuring inhibition. Preliminary results indicate that T. gondii follows mode-one and mode-two killing with relation to time after exposure to H2O2, implying a role for OH. and the induction of a DNA repair mechanism. The same model was used to assess inhibition of E. bovis growth that was more susceptible, being inhibited to 50% by 10(-5) M (10 microM) H2O2. Both parasites were susceptible to the effects of xanthine-xanthine oxidase that releases a full complement of oxygen intermediates (H2O2, OH., (1)O2, and O2-). Adding quenchers or scavengers to the system confirmed that T. gondii was susceptible to products of the interaction of O2- and H2O2 (OH. and (1)O2), and that E. bovis sporozoites were at least partially susceptible to H2O2 and O2-, but extremely susceptible to OH.. These data were supported by studies on scavenging enzymes present in the parasites. Toxoplasma gondii was rich in superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPO), and E. bovis had less catalase and SOD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Susceptibility of Eimeria bovis and Toxoplasma gondii to oxygen intermediates and a new mathematical model for parasite killing. 276 Jul 59

Misonidazole (1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol) is an experimental anticancer drug. Reductive metabolism is thought to be important for the cytotoxicity of misonidazole. In this study, the DNA binding of misonidazole was examined after chemical and enzymatic reduction. Under anaerobic conditions, both rat liver microsomes and cytosol catalyzed the reductive metabolism and DNA binding of misonidazole. The misonidazole utilized in these studies was radiolabeled on the side chain. The adduct(s) formed was too unstable for structural analysis. Little or no metabolism of misonidazole was detected in aerobic incubations. Likewise, very little DNA binding occurred in the presence of oxygen. Xanthine oxidase, a model nitroreductase, also was capable of catalyzing the DNA binding of misonidazole. However, unlike the xanthine oxidase catalyzed DNA binding of carcinogenic nitropolycyclic aromatic hydrocarbons, the DNA binding of misonidazole was not increased at slightly acidic pH. The putative reactive intermediate, the N-hydroxylamine, was synthesized by zinc reduction of misonidazole. The DNA binding of the N-hydroxylamine derivative increased with increasing pH. The observed pH dependence of the reactions with DNA is similar to other heterocyclic N-hydroxylamines, but is in contrast to the reactivity of a number of aromatic N-hydroxylamines.
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PMID:Reductive metabolism and DNA binding of misonidazole. 279 16

Potassium superoxide (KO2) and xanthine-xanthine oxidase (X-XO), which are known generating systems for the superoxide anion, have different inactivating actions on Bacillus subtilis transforming DNA in vitro. Superoxide dismutase and CuSO4 enhanced the inactivation for KO2, but not for X-XO. Mannitol, a hydroxyl radical scavenger, protected against the inactivation by X-XO, but not by KO2. The results obtained with X-XO were consistent with the involvement of Fenton reactions, in which hydroxyl radical is the reactive species that ultimately causes damage. On the other hand, KO2-induced inactivation was partly due to the effect of H2O2. Differences in inactivation between the KO2 and X-XO systems may result from the different rates of production of the superoxide anion.
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PMID:Comparison of the inactivation of Bacillus subtilis transforming DNA by the potassium superoxide and xanthine-xanthine oxidase systems for generating superoxide. 282 44

An antigen histochemically localized in the nuclei and cytoplasmic granules of normal and leukemic human myeloid cells has been identified as myeloperoxidase (MPO; EC 1.11.1.7). The localization and amount of the enzyme was determined by using a murine monoclonal antibody designated H-43-5 raised against nuclear proteins derived from human promyelocytic HL-60 leukemia cells. The highest amount of nuclear MPO (3.5 micrograms per 10(6) nuclei) was found in granulocytes; less than half of this amount was detected in nuclei from HL-60 cells. Still lower levels were found in nuclei from monocytes and a series of human monomyelocytic leukemia cells. MPO from HL-60 cells was purified by immunoaffinity chromatography and fractionated into three components (forms I, II, and III) by CM-cellulose chromatography. Chromatography of these MPO forms on DNA-Sepharose columns confirmed that all three forms of MPO were tightly bound to DNA with apparent relative affinities in the order of form III greater than form II greater than form I. The affinity of MPO form III for DNA was sufficient to enable the formation and elution of DNA-MPO complexes during size-exclusion chromatography at high ionic strength and neutral pH. This form of MPO was also able to shield DNA from strand scission induced by active oxygen species generated by xanthine oxidase acting aerobically on xanthine. These data suggest that intranuclear MPO may help to protect DNA against damage resulting from oxygen radicals produced during myeloid cell maturation and function.
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PMID:Myeloperoxidase: a myeloid cell nuclear antigen with DNA-binding properties. 282 20

The rate of oxyradical generation by a xanthine oxidase-xanthine system to acutely cause DNA strand breakage in Chinese hamster ovary cells was studied in a phosphate-buffered saline system. DNA strand breakage, measured by a fluorometric procedure, was found to increase curvilinearly as a function of oxyradical generation. Results of studying the ability of 5 mM mannitol, 10 mM dimethylthiourea, 300 micrograms superoxide dismutase/ml, or 1 mg catalase/ml to interfere with DNA damage at a high rate of oxyradical production best supported a hydrogen peroxide-promoted mechanism for DNA breakage.
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PMID:Acute effects of a superoxide radical-generating system on DNA double-strand stability in Chinese hamster ovary cells. Determination by a modified fluorometric procedure. 283 51

In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks.
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PMID:Oxidant-induced DNA damage of target cells. 284 65

Repair enzyme-containing extracts from a variety of cell types are used to analyse and compare DNA damage induced by oxygen radicals and excited molecules. The differing potentials of these extracts for recognising DNA damage leads to characteristic DNA damage profiles after treatment with superoxide (xanthine/xanthine oxidase), gamma-rays, chemically generated singlet oxygen, photosensitizers (rose bengal, methylene blue), UV254 and a 1,2-dioxetane. Three different types of damage profiles are distinguished and assigned to the predominant action of hydroxyl radicals, singlet oxygen or to the photoexcitation of thymine residues. The method applied in this study allows the analysis of DNA damage and the identification or exclusion of the participation of different ultimate reactive species without chemical identification of the lesions.
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PMID:DNA damage by oxygen radicals and excited state species: a comparative study using enzymatic probes in vitro. 284 22

The 32P-postlabeling technique was used to qualitatively establish the pattern of DNA adduct formation in mammary tissue and liver following administration of 1-nitropyrene to female Sprague-Dawley rats. 1-Nitropyrene (100 mg/kg b.w.) was administered by gavage in trioctanoin and the rats were sacrificed 24 h later. DNA was isolated from mammary fat pads and liver, enzymatically hydrolyzed to deoxyribonucleoside-3'-monophosphates and then converted to [5'-32P]3',5'-bisphosphates. The polyethyleneimine-cellulose (PEI-cellulose) TLC 32P-fingerprints revealed the presence of multiple putative adducts in the mammary fat pads and in the livers. To investigate the role of nitroreduction in the formation of these adducts, calf thymus DNA was incubated with [3H]1-nitropyrene in vitro in the presence of xanthine oxidase. The DNA was isolated and analyzed by the 32P-postlabeling technique. A major adduct spot was detected and confirmed as N-(deoxyguanosin-8-yl)-1-aminopyrene. This adduct cochromatographed with a minor in vivo adduct of DNA obtained from mammary fat pads and livers. However, the major adducts detected in vivo did not appear to originate from simple nitroreduction of 1-nitropyrene. The results of this study suggest that other metabolic pathways, such as ring oxidation, or ring oxidation followed by nitroreduction, may be responsible for the putative 1-nitropyrene-DNA adducts observed in mammary fat pads and livers of female Sprague-Dawley rats.
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PMID:32P-postlabeling analysis of 1-nitropyrene-DNA adducts in female Sprague-Dawley rats. 291 May 23

Active oxygen species are suspected as being a cause of the cellular damage that occurs at the site of inflammation. Phagocytic cells accumulate at these sites and produce superoxide ion, hydrogen peroxide and hydroxyl radical. The ultimate killing species, the cellular target and the mechanism whereby the lethal injury is produced are unknown. We exposed mouse fibroblasts to xanthine oxidase and acetaldehyde, a system which mimics the membrane of phagocytic cells in terms of production of oxygen species. We observed that the generation of these species produced DNA strand breaks and cellular death. The metal chelator o-phenanthroline completely abolished the former effect, and at the same time it effectively protected the cells from lethal injuries. Because complexing iron o-phenanthroline prevents the formation of hydroxyl radical by the Fendon reaction (Fe(II) + H2O2----Fe(III) + OH- + OH.), it is proposed that most of the cell death and DNA damage are brought about by OH radical, produced from other species by iron-mediated reactions.
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PMID:Protection of mammalian cells by o-phenanthroline from lethal and DNA-damaging effects produced by active oxygen species. 299 16

The ionic complex between lysozyme and either Escherichia coli DNA or pBR322 DNA was not crosslinked by two systems capable of producing nanomolar amounts of hydroxyl radicals, the oxidation of xanthine by xanthine oxidase and the iron catalyzed oxidation of ascorbic acid. Nor did effective crosslinking occur with micromolar quantities of hydroxyl radicals raised by the addition of adenosine nucleotides to ferrous iron and hydrogen peroxide. In this case, radical content was estimated by colorimetric analysis of formaldehyde following hydroxyl radical oxidation of dimethyl sulfoxide. Similar amounts of radicals generated by pulse radiolysis in a nitrous oxide atmosphere failed also to induce crosslinking. These findings do not support a role for hydroxy radicals in the N-acetoxy-2-acetylaminofluorene induced crosslinking of DNA to lysozyme proposed earlier.
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PMID:Hydroxyl radicals do not crosslink a DNA-lysozyme complex. 299 38


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