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)

14,15-3H-Norethisterone-4 beta, 5 beta-epoxide, a metabolite of norethisterone, was incubated with several proteins and nucleic acids. After 30 min incubation 0.19 nmol of the epoxide were irreversibly bound per mg albumin which contains free sulfhydryl groups; proteins without SH-groups, such as concanavalin A, gamma-globulin, DNA and RNA, did not irreversibly bind norethisterone epoxide. A superoxide (O2) generating enzyme system comprised of xanthine oxidase and hypoxanthine was capable of catalyzing the irreversible binding of the parent compound, norethisterone, to albumin, indicating that an oxidation product was formed which reacted with the protein. When norethisterone epoxide was incubated for 60 min with hepatic microsomes of rats in absence of NADPH, about 2.0 nmol of the epoxide were irreversibly incorporated per mg microsomal protein. This binding was increased to 5.2 nmol by addition of a NADPH regenerating system. Addition of glutathione and cytosol decreased only the NADPH-dependent protein binding; phenobarbital pretreatment of rats induced this NADPH-dependent binding of norethisterone epoxide to microsomal protein by a factor of 2. In presence of NADPH, binding of the epoxide to microsomal protein depended on substrate concentration used. The results indicate that norethisterone epoxide is able to chemically react with proteins. In addition, hepatic microsomal enzymes convert the epoxide to another metabolite which also can react with proteins.
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PMID:Irreversible protein binding of norethisterone (norethindrone) epoxide. 0 5

The degradation of DNA by bleomycin was studied in the absence and in the presence of added reducing agents, including 2-mercaptoethanol, dithiothreitol, reduced nicotinamide adenine dinucleotide phosphate, H2O2, and ascorbate, and in the presence of a superoxide anion generating system consisting of xanthine oxidase and hypoxanthine. In all cases, breakage of DNA was inhibited by low concentrations of chelators; where examined in detail, deferoxamine mesylate was considerably more potent than (ethylenedinitrilo)tetraacetic acid. Iron was found to be present in significant quantities in all reaction mixtures. Thus, the pattern of inhibition observed is attributed to the involvement of contaminating iron in the degradation of DNA by bleomycin. Cu(II), Zn(II), and Co(II) inhibit degradation of DNA by bleomycin and Fe(II) in the absence of added reducing agents. A model is proposed in which the degradation of DNA in these systems is dependent on the oxidation of an Fe(II)-bleomycin-DNA complex.
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PMID:Effect of chelating agents and metal ions on the degradation of DNA by bleomycin. 8 Feb 26

A 25-year-old white man with gout and nephropathy and with a previous reaction to allopurinol was given a trial dose of oxypurinol. He developed malaise, a generalized erythematous reaction with edema, pruritus, and emesis; this was clinically identical to the reaction he experienced with allopurinol. When the patient's lymphocytes were exposed in vitro to oxypurinol and allopurinol, increased DNA synthesis was observed, suggesting an immunologic basis for the reaction. This patient indicates that clinical cross reactivity to allopurinol and oxypurinol does occur and may be of an immunologic basis. There is a need for additional xanthine oxidase inhibitors for such patients.
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PMID:Allergic reaction to allopurinol with cross-reactivity to oxypurinol. 13 55

Acetylcholinesterase (AchE) is reported to have a narrowly restricted distribution among human tissues. Three strains of human fibroblasts which are trisomic for chromosome 2 had an average level of AchE activity over 28 times higher than the average level in 19 control strains of human fibroblasts. In contrast, the mean pseudocholinesterase activity of the trisomy-2 strains did not differ appreciably, or significantly, from the mean for the control strains. The 19 control strains included 10 strains trisomic for autosomes other than 2, and 9 euploid strains. Our estimate of the mean AchE activity in the control strains did not differ significantly from zero and might, in any case, have originated from a minute amount of activity contributed to the cells by an esterase in our culture medium. Despite the striking elevation of AchE activity in fibroblasts trisomic for chromosome 2, extracts of these cells had only about 1.5% of the specific AchE activity (per microgram DNA) present in extracts of human cerebral cortex. None of the 22 strains studied had detectable activity for two other enzymes which, like AchE, have a restricted distribution among human tissues: xanthine oxidase and choline acetyltransferase.
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PMID:Evidence for a striking increase in acetylcholinesterase activity in cultured human fibroblasts which are trisomic for chromosome two. 69 21

Milk fat globule membranes (MFGM) and rough endoplasmic reticulum (RER) membranes were isolated from milk and lactating mammary gland from the cow and were characterized by biochemical and electron microscope methods in terms of gross composition (proteins, phospholipids, neutral lipids, cholesterol, RNA, and DNA) and purity. Both fractions contained significant amounts of a b-type cytochrome with several properties similar to those of cytochrome b5 from liver, as well as a rotenone-insensitive NADH- and NADPH-cytochrome c reductase. The b-type cytochrome content in the apical plasma membrane-derived MFGM was of the same order of magnitude as it was in RER membranes. It was characterized by a high resistance to extraction by low- and high-salt concentrations and nonionic detergents. MFGM contained much more flavin and much higher activities of xanthine oxidase than the RER membranes. The same redox components were found in MFGM and mammary RER from women, rats, mice, and goats, but in absolute contents great differences between the species were noted. The cytochromes described here differed from liver cytochrome b5 in some spectral properties. The alpha-band of the reduced hepatic cytochrome b5 is asymmetric with a maximum at 555 nm that is split into two distinct peaks at low temperatures. The alpha-band of the b-type cytochromes from MFGM and mammary RER appears as one symmetrical peak at about 560 nm that is not split at low temperatures. When treated with cyanide, MFGM and mammary microsomes showed difference spectra of a reduced b-type cytochrome. Under the same conditions, liver microsomes gave a completely different spectrum. These findings demonstrate the presence of a b-type cytochrome and associated redox enzymes in MFGM, i.e., a derivative of the apical cell surface membrane that is regularly used for envelopment of the milk fat globule during secretion.
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PMID:Redox constituents in milk fat globule membranes and rough endoplasmic reticulum from lactating mammary gland. 85 33

A group of substituted 5,8-quinolinequinones which exhibit antineoplastic activity and which are structurally related to the antitumor antibiotic streptonigrin induce single strand cleavage of PM2 covalently-closed circular-DNA (ccc-DNA) when reductively activated. The cleavage which is detected by an ethidium fluorescence assay is specifically enhanced by cuprous and ferrous ion and is selectively inhibited by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) and by free radical scavengers. Independent generation of the superoxide ion by xanthine-xanthine oxidase (EC 1.2.3.2) also cleaves PM2 DNA and therefore a chemical mechanism for the scission process induced by the streptonigrin analogues is formulated. A correlation between rate of PM2 ccc-DNA cleavage and inhibition of Walker carcinosarcoma 256 is observed.
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PMID:Studies related to antitumor antibiotics. Part VIII. Cleavage of DNA by streptonigrin analogues and the relationship to antineoplastic activity. 127 71

DNA adduct formation in the liver of B6C3F1 mice after administration of 1-nitropyrene (1-NP) was shown by the 32P-postlabeling technique. The major adduct was not N-(deoxyguanosin-8-yl)-1-aminopyrene, which was easily formed in in vitro nitroreduction of 1-NP in the presence of DNA, but the major spots migrated to the same position as the in vitro DNA adduct spots of K-region epoxides of 1-NP (1-NP 4,5- and 9,10-oxide). 1-NP oxides formed by the oxidative activation of 1-NP in the liver were excreted into the bile as detoxified glutathione conjugates which were changed to cysteine conjugates in the upper intestinal tract. The cysteine conjugates were degraded by cysteine conjugate beta-lyase (beta-lyase) of intestinal microflora in the lower intestinal tract. The mutagenicity of cysteine conjugates of 1-NP oxides for Salmonella typhimurium was enhanced by addition of beta-lyase and was decreased by addition of aminooxyacetic acid, a beta-lyase inhibitor. The in vitro binding of the cysteine conjugates to calf thymus DNA was increased by addition of beta-lyase and xanthine oxidase. We administered glutathione conjugates of 1-NP oxides to two groups of mice that had been treated with antibiotics or saline by gavage and analyzed the DNA adducts in the lower intestinal mucosa. The specific DNA adducts were detected in the saline-treated group but not in the antibiotics-treated group. These results suggest that intestinal microflora play an important role in activation of glutathione conjugates of 1-NP oxides.
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PMID:Role of intestinal microflora in metabolism of glutathione conjugates of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide. 130 95

The formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthesized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase in the presence of BABQ derivatives. At low concentrations (< 10 microM) some BABQ derivatives turned out to inhibit the production of superoxide and hydroxyl radicals by xanthine oxidase, while the effect on the xanthine-oxidase-induced production of hydrogen peroxide was much less pronounced. Induction of DNA strand breaks by reactive oxygen species generated by xanthine oxidase was also inhibited by BABQ derivatives. The DNA damage was comparable to the amount of hydroxyl radicals produced. The inhibiting effect on hydroxyl radical production can be explained as a consequence of the lowered level of superoxide, which disrupts the Haber-Weiss reaction sequence. The inhibitory effect of BABQ derivatives on superoxide formation correlated with their one-electron reduction potentials: BABQ derivatives with a high reduction potential scavenge superoxide anion radicals produced by xanthine oxidase, leading to reduced BABQ species and production of hydrogen peroxide from reoxidation of reduced BABQ. This study, using a unique series of BABQ derivatives with an extended range of reduction potentials, demonstrates that the formation of superoxide and hydroxyl radicals by bioreductively activated antitumor quinones can in principle be uncoupled from alkylating activity.
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PMID:Redox cycling of potential antitumor aziridinyl quinones. 133 33

The biochemical mechanisms underlying blood lymphoid cell genome destabilization in patients with HIV infection have been analyzed. Lymphocytes from HIV patients are characterized by increasing intensity of free radical oxidation together with activation of the xanthine oxidase D-form conversion into the O-form, enhanced activity of UV-endonuclease, and intensification of prooxidant-induced proteolysis. These changes increasing with the progress of the disease with a maximum at the AIDS stage form a metabolic basis for labilization of the lymph cell genome. The degree of biochemical manifestations of genome instability (levels of chromatin degradation products and intensity of formation of one-filament nicks of DNA) increase in the dynamics of HIV-infection. The data obtained are discussed in terms of the author's conception on the origin of AIDS from retroposons (retrotransposons?). A hypothesis is postulated on accumulation of autonomous genetic information on the basis of genome labilization under the influence of genotoxic factors. Clinico-biochemical data on the appearance of HIV proteins (p17, p24) in the blood of patients (previously negative for all HIV markers) in the presence of transfusions of HIV-negative blood and UV-irradiation of the autoblood are also discussed from this standpoint.
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PMID:[Genomic instability and AIDS]. 133 9

Vascular smooth muscle cells (VSMCs) proliferate in response to arterial injury. Recent findings suggest that, in addition to platelet-derived growth factors, growth factors from inflammatory cells and endothelial cells at the site of injury may contribute to VSMC proliferation. We hypothesized that a common mechanism by which endothelial cells and inflammatory cells stimulate VSMC growth could be the active oxygen species (i.e., O2-, H2O2, and .OH) generated during arterial injury. Using xanthine/xanthine oxidase to generate active oxygen species, we studied the effects of these agents on VSMC growth. Xanthine/xanthine oxidase (100 microM xanthine and 5 microunits/ml xanthine oxidase) stimulated DNA synthesis in growth-arrested VSMCs by 180% over untreated cells. Administration of the scavenging enzymes superoxide dismutase and catalase demonstrated that H2O2 was primarily responsible for xanthine/xanthine oxidase-induced VSMC DNA synthesis. H2O2 directly increased VSMC DNA synthesis and cell number (maximal at 200 microM) but decreased DNA synthesis of endothelial cells and fibroblasts. This effect was protein kinase C independent: sphingosine, a potent protein kinase C inhibitor, failed to block H2O2-induced VSMC DNA synthesis. H2O2 (200 microM) stimulated c-myc and c-fos mRNA levels by fourfold and 20-fold, respectively, as compared with quiescent levels. In contrast to DNA synthesis, H2O2 induction of c-myc and c-fos mRNA was primarily protein kinase C dependent. These findings show that H2O2 specifically increases VSMC DNA synthesis and suggest a role for this oxidant in intimal proliferation, especially after arterial injury.
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PMID:Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. 2411 68


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