UNIPROT:P47989 - FACTA Search

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Query: UNIPROT:P47989 (xanthine oxidase)
8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

V79mut1 cells are resistant to the toxic effects of 5-hydroxymethyl-2'-deoxyuridine (hmdUrd) and are deficient in the DNA repair enzyme hydroxymethyluracil-DNA glycosylase (hmUDG). We have therefore proposed that the toxicity of hmdUrd results from the repair of the lesion from DNA. In order to clarify the biological role of hmUDG, we have determined whether the repair-deficient cells showed resistance or sensitivity to the toxic or mutagenic effects of other DNA-damaging agents. Cells were exposed to hmdUrd, ionizing or ultraviolet radiation, to the alkylating agent MNNG, and to oxidative stress produced by hypoxanthine/xanthine oxidase, glucose/glucose oxidase, nitric oxide donor SNAP, or to H2O2. The V79mut1 cells did not show increased mutagenesis in response to hmdUrd. Relative to the V79 parent cells, the V79mut1 cells were not markedly altered in sensitivity to oxidizing agents and ionizing radiation (which produce hmdUra in DNA). The repair-deficient cells wee equally sensitive as the parent V79 cells to DNA damage induced by ultraviolet radiation or by MNNG. No significant differences were seen between the parent and the repair-deficient cells in terms of synthesis of poly(ADP-ribose) in response to damage or in their sensitization to 3-aminobenzamide. Thus, the loss of the 5-hydroxymethyluracil (hmUra)-DNA glycosylase activity in mammalian cells in culture confers no obvious deleterious effect on cell survival or mutagenicity in response to a wide range of DNA damage. These studies indicate that the major lesion known to be repaired by hmUra-DNA glycosylase, an hmUra residue replacing thymine, is produced in cells only in small quantities as the result of exposure to common DNA-damaging agents. These results raise the possibility that hmUra-DNA glycosylase may have evolved to respond to other lesions than hmUra residues formed from the oxidation of thymine.
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PMID:Lack of phenotypic alteration of hmUra-DNA glycosylase-deficient hamster cells exposed to DNA-damaging agents. 910 Aug 52

The role of nitric oxide (NO) and oxygen free radicals in cyclosporine (CsA) nephrotoxicity was investigated using L-arginine, an NO substrate, and allopurinol, a xanthine oxidase inhibitor (involved in the formation of oxygen radicals) in an experimental model with Wistar rats. CsA, administered at 15 mg/kg/body weight (BW) subcutaneously for 10 days, caused a decrease in glomerular filtration rate, with inulin clearance of 0.33+/-0.04 vs. 1.11+/-0.06 ml/min/100 g BW (P<0.01 vs. control). L-Arginine, 1.5% in drinking water 5 days before and during CsA administration, partially protected the animals against this fall in glomerular filtration rate, with inulin clearance of 0.68+/-0.03 ml/min/100 g BW (P<0.01 vs. CsA). Allopurinol, at 10 mg/kg/BW by gavage, also had a protective action, with inulin clearance of 0.54+/-0.04 ml/min/100 g (P<0.01 vs. CsA). CsA caused an elevation in NO production, as assessed by urinary excretion of its metabolites, nitrite and nitrate (NO2 and NO3; 0.836+/-0.358 vs. 0.107+/-0.019 nmol/microg creatinine). NO production was as much as threefold higher in the L-arginine group (1.853+/-0.206 nmol/g creatinine). This CsA effect is probably related to its vasoconstrictive stimulus. Supplementation with L-arginine, which provides more substrate for NO formation, may enhance vasodilatation and consequently reduce the impairment of renal function. The protection provided by allopurinol may be related to the reduced formation of oxygen radicals, preventing the deleterious effects of lipid peroxidation.
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PMID:L-Arginine and allopurinol protect against cyclosporine nephrotoxicity. 913 66

Aspirated gastric contents can evoke multiorgan failure. We hypothesized that secondary intestinal epithelial dysfunction after lung damage would be mediated by xanthine oxidase (XO) and antagonized by endogenous gut nitric oxide (NO). Isosmotic saline or HCl solutions were instilled intratracheally in anesthetized rats, and intestinal injury was assessed 190 min later by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA clearance) and gut wall neutrophil population density. Intratracheal HCl increased 51Cr-EDTA clearance, and this transepithelial leak was attenuated by either systemic L-arginine or intraluminal NO and by chronic dietary pretreatment with allopurinol or sodium tungstate. Conversely, lung damage-induced gut leak was exaggerated by NO synthase inhibition or intravenous XO administration. Intratracheal HCl also increased intestinal wall neutrophil density and myeloperoxide activity. We conclude that two enzymatic systems involved in remote gut barrier dysfunction after endobronchial acidification are XO as mediator and NO synthase as antagonist.
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PMID:Nitric oxide attenuates and xanthine oxidase exaggerates lung damage-induced gut injury. 914 17

Nitric oxide (NO.) and superoxide (O2-) are inflammatory mediators. Their formation seems to be associated with apoptotic and/or necrotic cell death in diseases such as mesangioproliferative glomerulonephritis in which the early phase of mesangiolysis is linked to significant NO. production. Notably, mesangial cells (MC) not only generate NO. but also O2- after cytokine stimulation. Here we investigated the interrelation between NO. and O2- in MC death by generating both radicals with the use of NO donors (S-nitrosoglutathione, spermine-NO) and O2(-)-generating systems (2,3-dimethoxy-1,4-naphtoquinone, hypoxanthine/xanthine oxidase). Exogenously supplied NO. or O2- in a concentration-dependent manner induced apoptosis and/or necrosis. Apoptosis is characterized by chromatin condensation and DNA fragmentation in contrast to necrotic cytoplasmatic membrane rupture. Noteworthy, coincubation of NO. and O2- was cross-protective. Maximum protection required the existence of a balanced NO./O2- ratio. Analysis in cytokine-stimulated MC suggests endogenous radical formation, which may participate in modulating apoptosis. Manipulation of the endogenous NO./O2- ratio by exogenous, sublethal S-nitrosoglutathione in addition to cytokines produced death, which was antagonized by inducible nitric oxide synthase (iNOS) inhibition. Moreover, pyrrolidine dithiocarbamate supplementation, which down-regulates iNOS expression and blocks superoxide dismutase activity, initiates apoptosis. Our results imply the participation of reactive nitrogen and oxygen species in determining life and death of MC.
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PMID:The balance between nitric oxide and superoxide determines apoptotic and necrotic death of rat mesangial cells. 914 12

Superoxide rapidly oxidizes nitric oxide (NO) to form peroxynitrite, thus terminating the biological activity of NO. The aims of our study were to determine if superoxide alters the motor function of the sphincter of Oddi and to localize the antioxidant enzymes in the sphincter of Oddi. Immunostaining was performed and enzyme activities were measured in the sphincter of Oddi. In physiological experiments, force-displacement transducers recorded tension in the spontaneously contracting sphincter of Oddi and after electrical field stimulation (EFS) of precontracted sphincter of Oddi. Superoxide was generated by the addition of xanthine with xanthine oxidase, superoxide radicals were scavenged by the addition of superoxide dismutase (SOD), and catalase or SOD was inhibited by diethyldithiocarbamic acid. Immunostaining demonstrated SOD and catalase immunoreactivity in ganglia situated at the serosal surface of the circular muscle. Total SOD activity was 202 +/- 12 U/mg. Generation of superoxide or inhibition of SOD increased the contractile frequency and decreased relaxation after EFS. We conclude that superoxide alters sphincter of Oddi motor function, and the presence of superoxide scavenging enzymes in enteric plexuses suggests that they may regulate sphincter of Oddi neuromuscular function by clearing endogenous superoxide.
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PMID:The role of antioxidant enzymes in the control of opossum sphincter of Oddi motility. 917 13

Reactive oxygen species (ROS) play an important role in the pathogenesis of ischemia-reperfusion injury. Extracellular H2O2 generation from bovine pulmonary artery endothelial cells (EC) is known to increase in response to anoxia-reoxygenation (A-R). To determine potential sources of intracellular ROS formation in EC in response to A-R, a fluorometric assay based on the oxidation of 2',7'-dichlorofluorescin was used. Intracellular ROS production declined 40% during 6 h of anoxia (P < 0.05). After A-R, the rates of intracellular ROS formation increased to 148 +/- 9% (P < 0.001) that of normoxic EC (100 +/- 3%). In EC exposed to A-R, allopurinol and NG-methyl-L-arginine (L-NMMA), inhibitors of xanthine oxidase (XO) and nitric oxide synthase (NOS), respectively, reduced intracellular ROS formation by 25 +/- 1% (P < 0.001) and 36 +/- 4% (P < 0.01). Furthermore, at low doses (i.e., 20 microM), deferoxamine and diethylenetriaminepentaacetic acid (DTPA) significantly inhibited intracellular ROS formation. However, at 100 microM, only deferoxamine caused further reduction in DCF fluorescence. In summary, EC respond to A-R by generating increased amounts of XO- and NOS-derived intracellular ROS. The inhibition, to a similar extent, caused by allopurinol and L-NMMA, as well as the effect of deferoxamine and DTPA suggest that the ROS detected is peroxynitrite. Based on these findings and previous work, we conclude that EC generate ROS in response to A-R from at least two different sources: a plasma membrane-bound NADPH oxidase-like enzyme that releases H2O2 extracellularly and XO, which generates intracellular O2-, which in turn may react with nitric oxide to form peroxynitrite.
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PMID:Intracellular generation of reactive oxygen species in endothelial cells exposed to anoxia-reoxygenation. 917 54

Because neutrophils contribute to reperfusion injury associated with acute myocardial infarction (MI), and because tissue plasminogen activator (tPA) is often used in the management of MI, we evaluated the effect of tPA on superoxide (O2.-) production by human neutrophils in vitro. We found that adding increasing amounts of tPA significantly (r = 0.89, P < 0.025) and progressively reduced O2.- generation by neutrophils treated with phorbol myristate acetate (PMA) in vitro. Furthermore, adding tPA that had been previously treated with the protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone HCl (PPACK), also decreased neutrophil O2.- generation in vitro (P < 0.05). In contrast, adding L-arginine, a component of the tPA preparation and a precursor of nitric oxide (NO), did not inhibit PMA-induced neutrophil O2.- production. Also, adding increasing concentrations of tPA did not reduce (P > 0.05) the concentrations of O2.- produced by xanthine oxidase (XO) in vitro. Our findings suggest that tPA reduces neutrophil O2.- generation by a mechanism that is not related to L-arginine, is not dependent on tPA proteolytic activity, and is not a function of direct scavenging. This property may account for some of the effectiveness of tPA in the treatment of MI and/or make tPA valuable for treating acute respiratory distress syndrome (ARDS) or other inflammatory disorders involving neutrophil O2.- production.
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PMID:Tissue plasminogen activator (tPA) inhibits human neutrophil superoxide anion production in vitro. 917 19

The role of superoxide anion (O2-) and nitric oxide (NO) in the host defense mechanism against Salmonella typhimurium (LT-2) was examined by focusing on xanthine oxidase (XO) as an O2(-)-generating system and on inducible NO synthase (iNOS). When ICR mice were infected with a 0.1 50% lethal dose (2 x 10(5) CFU) of S. typhimurium, bacterial growth in the liver reached a peak value 3 days after infection (10(4.32) CFU/g of liver) and decreased thereafter. XO activity in the liver became maximum at 7 days after infection; the value was 34.6 +/- 1.4 mU/g of liver at 7 days (compared with 11.0 +/- 1.3 mU/g of liver before infection). The time profile of NO production in the liver as determined by electron spin resonance spectroscopy was consistent with that of XO activity. Histological examination of infected liver showed the formation of multiple microabscesses with granulomatous lesions consisting of polymorphonuclear cells and mononuclear cells, and iNOS-expressing cells were localized in the confined areas of the microabscesses. When XO inhibitors such as allopurinol and 4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine (AHPP) were administered to the infected mice, the mortality of the mice was significantly increased (10 of 21 and 11 of 20 for the allopurinol- and AHPP-treated groups, respectively, versus 2 of 20 for control mice), and bacterial growth was significantly enhanced. A similar exacerbation of the infection was obtained with N(omega)-monomethyl-L-arginine (L-NMMA) treatment of the mice. Of considerable importance is that granuloma formation in the liver was poorly developed by treatment with either XO inhibitors or L-NMMA. These results suggest that XO and NO play an important role in the antimicrobial mechanism against S. typhimurium in mice.
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PMID:Induction of nitric oxide synthesis and xanthine oxidase and their roles in the antimicrobial mechanism against Salmonella typhimurium infection in mice. 919 69

Dimalonic acid C60 (10(-5) M), a new fullerene derivative, produced an augmentation of phenylephrine-induced tone and reduced both the acetylcholine-induced maximum relaxation and the amplitude of substance P (10(-8) M)-induced relaxation in endothelium-containing thoracic aorta of rabbit; the acetylcholine- and substance P-induced relaxation was restored in the presence of superoxide dismutase (250 U/ml). Dimalonic acid C60 (10(-5) M) did not influence the phenylephrine-induced contractile response in the absence of endothelium, but the acetylcholine-induced relaxation was eliminated by removal of the endothelium. Superoxide anion generation, using hypoxanthine (1 mM)/xanthine oxidase (16 mU/ml), reduced the acetylcholine-induced relaxation and produced an augmentation of phenylephrine-induced tone in endothelium-containing strips; these effects were negated by the addition of superoxide dismutase (250 U/ml). A nitric oxide-generating agent, S-nitroso-N-acetylpenicillamine, caused relaxation of aorta without endothelium in a concentration-dependent manner, and the concentration-response curve was shifted to the right in the presence of dimalonic acid C60. This inhibitory effect of dimalonic acid C60 was also masked in the presence of superoxide dismutase. Sodium nitroprusside-induced relaxation was not affected by either dimalonic acid C60 or superoxide dismutase. These observations suggest that dimalonic acid C60 inhibits endothelium (nitric oxide)-dependent agonist-induced relaxation through the production of superoxide.
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PMID:Inhibitory effects of a fullerene derivative, dimalonic acid C60, on nitric oxide-induced relaxation of rabbit aorta. 920 May 57

Giardia lamblia trophozoites were incubated for 2 h with activated murine macrophages, nitric oxide (NO) donors or a superoxide anion generator (20 mU/ml xanthine oxidase plus 1 mM xanthine). Activated macrophages were cytotoxic to Giardia trophozoites (approximately 60% dead trophozoites). The effect was inhibited (> 90%) by an NO synthase inhibitor (200 microM) and unaffected by superoxide dismutase (SOD, 300 U/ml). Giardia trophozoites were killed by the NO donors, S-nitroso-acetyl-penicillamine (SNAP) and sodium nitroprusside (SNP) in a dose-dependent manner (LD50 300 and 50 microM, respectively). A dual NO-superoxide anion donor, 3-morpholino-sydnonimine hydrochloride (SIN-1), did not have a killing effect in concentrations up to 1 mM. However, when SOD (300 U/ml) was added simultaneously with SIN-1 to Giardia, a significant trophozoite-killing effect was observed (approximately 35% dead trophozoites at 1 mM). The mixtures of SNAP or SNP with superoxide anion, which yields peroxynitrite, abolished the trophozoite killing induced by NO donors. Authentic peroxynitrite only killed trophozoites at very high concentrations (3 mM). These results indicate that NO accounts for Giardia trophozoites killing and this effect is not mediated by peroxynitrite.
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PMID:Role of nitric oxide and superoxide in Giardia lamblia killing. 922 10

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