Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reactivity and toxicity of nitric oxide is modest in comparison to oxidants derived from nitric oxide. Exposure of Escherichia coli to 1 mM nitric oxide under aerobic or anaerobic conditions did not decrease viability of the bacteria. Peroxynitrite (1 mM), the reaction product of superoxide and nitric oxide, was completely bactericidal after 5 s. The nitrovasodilator, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), slowly decomposes to release both nitric oxide and superoxide and thereby produces peroxynitrite. SIN-1 killed E. coli in direct proportion to its concentration with an LD50 of 0.5 mM. Copper, zinc superoxide dismutase (50-400 units/ml) provided substantial but not complete protection against SIN-1 killing. Catalase (500-10,000 units/ml) partially protected in direct proportion to its concentration, while inactivated catalase was not protective. Superoxide dismutase and catalase together completely protected E. coli against SIN-1 toxicity. Oxy-hemoglobin eliminated both SIN-1 and peroxynitrite toxicity. The bactericidal activity of SIN-1 was further enhanced by pterin plus xanthine oxidase. Pterin plus xanthine oxidase alone or together with Fe3+ ethylenediamine tetraacetate produced no significant decrease in E. coli viability. Hydrogen peroxide was not directly toxic to the bacteria, but E. coli pretreated with hydrogen peroxide were more susceptible to peroxynitrite, SIN-1, and the aerobic oxidation products of nitric oxide. Hydrogen peroxide pretreatment did not increase significantly the toxicity of nitric oxide under anaerobic conditions. Our results suggest that peroxynitrite is far more toxic to E. coli than nitric oxide or its by products from aerobic oxidation.
 ...
PMID:The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. 784 Jun 33

On the basis of 32P-postlabeling analysis, treatment of rats with 1-nitropyrene (1-NP) resulted in the formation of multiple DNA adducts in the liver, mammary glands, and peripheral lymphocytes. The one adduct resulting from nitroreduction, N-(deoxyguanosin-8-yl)-1-aminopyrene, constitutes only a minor component among the adducts. In the present study, incubation of calf thymus DNA with mutagenic ring-oxidized metabolites of 1-NP in vitro in the presence and absence of xanthine oxidase also resulted in the formation of multiple adducts. On the basis of their chromatographic behavior, it appears that DNA adducts derived from such metabolites may have been formed in vivo; however, this needs to be confirmed. [3H]1-NP was given to male and female F344 rats and Sprague-Dawley rats by gavage at five dose levels in the range of 0.1 to 1000 micrograms/kg bw. This led to stable hemoglobin adducts accounting for 0.08 +/- 0.05% of the dose (n = 3 rats). The radioactivity associated with hemoglobin following administration of [3H]1-NP was cleared with a half-life of about 14 days, which is faster than that of unmodified erythrocytes in the rat (t1/2 = 30 days). Treatment of the hemoglobin with 1% HCl in acetone, to precipitate the globin, released the radioactivity; it was all bound to the heme moiety. The structures of the heme adducts have not been elucidated; yet, because of their stability, they may be useful as dosimeters for human exposure to 1-NP.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Development of methods to monitor exposure to 1-nitropyrene. 788 55

In this study, we prepared PolyHb-SOD-catalase (intermolecularly cross-linked hemoglobin, superoxide dismutase (SOD), and catalase). We found that PolyHb-SOD-catalase is effective in scavenging oxygen-derived free radicals. In the xanthine/xanthine oxidase system, the initial rate of cytochrome c reduction was 2.13 +/- 0.26 nmoles cyt. c/min for PolyHb alone. PolyHb- SOD-catalase reduced this to 0.56 +/- 0.08 nmoles cyt. c/min because of its ability to eliminate superoxide (O2-). Addition of PolyHb to 200 microM of hydrogen peroxide (H2O2), changed the H2O2 level slightly to 192 +/- 0.4 microM. Addition of PolyHb-SOD-catalase, on the other hand, lower the level to 41 +/- 0.3 microM. Results also show that both effects were dependent on the concentration of SOD-catalase cross-linked with hemoglobin. Oxidative challenge with H2O2 resulted in minimal changes in the absorbance spectra of PolyHb-SOD-catalase. With PolyHb, there were spectral changes reflecting the formation of methemoglobin and heme degradation. Furthermore, the amount of iron released, after incubation with 250 microM H2O2, was 6.8 +/- 1.8 micrograms/dl for PolyHb-SOD-catalase and 76.6 +/- 1.0 micrograms/dl for PolyHb. These results show that cross-linked SOD-catalase prevents oxidative reactions involving the hemoglobin component of PolyHb-SOD-catalase.
 ...
PMID:Cross-linked hemoglobin-superoxide dismutase-catalase scavenges oxygen-derived free radicals and prevents methemoglobin formation and iron release. 811 50

When Escherichia coli was incubated with xanthine oxidase and acetaldehyde, the killing of E. coli was accelerated by iron-EDTA but inhibited by hematin or hemoglobin. On the other hand, when E. coli was incubated with human neutrophils in the presence of phorbol myristate acetate (PMA), all of these iron species at concentrations of a few micromolar accelerated the inactivation of neutrophils and in so doing protected the E. coli from being killed by the neutrophils. The inactivation of the neutrophils was accompanied by an increase in lipid peroxidation and by a decrease in viability measured with trypan blue. This inactivation was inhibited by scavengers such as deoxyribose, mannitol, or thiourea. Desferrioxamine B and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) both inhibited the inactivation mediated by iron-EDTA, but had no effect on the hematin- or hemoglobin-mediated inactivation. Vanadium (vanadyl ion), an effective Fenton reagent, behaved in the same way as iron-EDTA relative to the effects of DMPO on neutrophil inactivation. These results led us to conclude that neutrophils were inactivated during PMA stimulation by OH radicals in the presence of iron-EDTA and by some other oxidizing species when hematin or Hb is present. Ascorbate enhanced the inactivation of neutrophils mediated by these iron species. Catalase was very effective in inhibiting neutrophil inactivation. Superoxide dismutase was not as effective but the combination with catalase was most effective.
 ...
PMID:The effect of hemoglobin, hematin, and iron on neutrophil inactivation in superoxide generating systems. 813 43

The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced pneumonia in mice was investigated. Experimental influenza virus pneumonia was produced with influenza virus A/Kumamoto/Y5/67(H2N2). Both the enzyme activity of NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased in the mouse lungs; increases were mediated by interferon gamma. Excessive production of NO in the virus-infected lung was studied further by using electron spin resonance (ESR) spectroscopy. In vivo spin trapping with dithiocarbamate-iron complexes indicated that a significant amount of NO was generated in the virus-infected lung. Furthermore, an NO-hemoglobin ESR signal appeared in the virus-infected lung, and formation of NO-hemoglobin was significantly increased by treatment with superoxide dismutase and was inhibited by N(omega)-monomethyl-L-arginine (L-NMMA) administration. Immunohistochemistry with a specific anti-nitrotyrosine antibody showed intense staining of alveolar phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate in the virus-infected lung. These results strongly suggest formation of peroxynitrite in the lung through the reaction of NO with O2-, which is generated by alveolar phagocytic cells and xanthine oxidase. In addition, administration of L-NMMA resulted in significant improvement in the survival rate of virus-infected mice without appreciable suppression of their antiviral defenses. On the basis of these data, we conclude that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice.
 ...
PMID:Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. 863 94

Inhaled nitric oxide (NO) may modify surfactant either by interacting with the surfactant complex or by changing the capacity of the proteins of the epithelial lining fluid to inhibit the surface activity. Natural surfactant was exposed to NO (80 parts/million) in air in vitro while the gas-liquid surface was cycled. In the presence or absence of oxidants (Fe2+, xanthine, xanthine oxidase), surfactant exposed to NO retained the high surface activity significantly better than control surfactants exposed to air. Two surfactant inhibitors, hemoglobin (Hb) and albumin, were separately exposed to NO. In contrast to albumin, NO-exposed Hb and methemoglobin (MetHb; 16-125 micrograms/ml) decreased the surface activity at low surfactant concentrations, whereas native Hb had no effect. Surfactant recovered by sedimentation after exposure to MetHb had decreased surface activity and contained MetHb, whereas Hb did not bind to surfactant. Acidic phospholipid phosphatidylglycerol increased the binding of MetHb to surfactant. The MetHb-induced decrease in surface activity was elicited in the presence of surfactant proteins, including a peptide mimicking surfactant protein B. MetHb (but not Hb) added to a low dose of exogenous surfactant decreased the efficacy of surfactant to improve the lung compliance of premature rabbits. We propose that inhaled NO promotes the surface activity of surfactant during tidal ventilation and that, in high-permeability lung edema and surfactant deficiency, inhaled NO increases the inhibition of surface activity by converting Hb to MetHb in the alveolar space.
 ...
PMID:A mechanism of nitric oxide-induced surfactant dysfunction. 880 11

High levels of glycosylated human hemoglobin impair nitric oxide-mediated responses. However, the percentage of glycosylation for which this effect is observed and the mechanisms involved are unknown. We tested endothelium-dependent relaxations caused by acetylcholine in rat aortic segments either in control conditions or after preincubation with increasing percentages of glycosylated human hemoglobin. Human hemoglobin (1 and 10 nmol/L) inhibited endothelium-dependent relaxations only when glycosylated at 9% or higher. We evaluated the effect of 14% glycosylated human hemoglobin on acetylcholine-evoked responses in vessels preincubated with scavengers of superoxide anions, hydroxyl radical, or hydrogen peroxide (superoxide dismutase, deferoxamine, and catalase, respectively); with inhibitors of xanthine oxidase, cyclooxygenase, or thromboxane synthase (allopurinol, indomethacin, and dazoxiben, respectively); with blockers of thromboxane A2/prostaglandin H2 or endothelin receptors (SQ 30741 and BQ-123); and with the precursor of nitric oxide synthesis L-arginine. Superoxide dismutase abolished the effect of glycosylated hemoglobin, and the other substances did not have any effect. Glycosylated hemoglobin at 14% did not modify either the vasoconstrictions induced by the blocker of nitric oxide synthase NG-nitro-L-arginine methyl ester or the relaxations evoked in deendothelialized vessels by sodium nitroprusside and 8-bromo-cGMP. However, it inhibited the vasodilations evoked by exogenous nitric oxide. Superoxide dismutase abolished this latter effect. We conclude that the threshold for glycosylated human hemoglobin (Hb A1) to inhibit endothelium-dependent relaxation is 9%. This effect is due to interference with endothelial nitric oxide by means of superoxide anion production.
 ...
PMID:Impairment of endothelium-dependent relaxation by increasing percentages of glycosylated human hemoglobin. Possible mechanisms involved. 884 82

The antioxidant activity of hemoglobin was examined by studying both its peroxidase activity and its interaction with the superoxide anion. The peroxidase activity of both the subunits (alpha and beta) was reduced with respect to the alpha 2 beta 2 tetramer and heme-oxidation was found to be associated with a decrease in this activity. Lucigenin-amplified chemiluminescence experiments have shown that at low pH, the presence of hemoglobin reduces the level of superoxide anion generated by the xanthine/xanthine oxidase system (met-Hb is more efficient in reducing the level of O2- than oxy-hemoglobin). These results confirm that hemoglobin may be of importance in providing protection against oxidative damage to erythrocytes.
 ...
PMID:Antioxidant activities of different hemoglobin derivatives. 946 55

We investigated the generation of nitric oxide (NO) by H2O2-dependent peroxidation of hydroxyurea in the presence of copper-containing proteins such as Cu,Zn-superoxide dismutase (Cu,Zn-SOD) or ceruloplasmin as a catalyst. In the reaction mixture of hydroxyurea, CuZn-SOD, and H2O2, NO generation was identified by measuring the specific electron spin resonance (ESR) signal of 2-phenyl-4, 4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). The ESR signal of the NO-hemoglobin adduct was also detected in human red blood cells during copper-catalyzed peroxidation of hydroxyurea. The NO production during peroxidation of hydroxyurea was quantified as NO2- formation, measured by using the Griess assay, the amount of NO2- was dependent on the concentrating of hydroxyurea of the reaction mixture. ESR spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) showed hydroxy radical (OH) generation in the reaction of H2O2 with either Cu,Zn-SOD or ceruloplasmin. Several OH scavengers, such as ethanol, thiourea, DMPO, and dimethylsulfoxide, and the metalchelating agent diethylenetriaminepentaacetic acid significantly inhibited NO generation from hydroxyurea. This indicates that NO release from hydroxyurea may be mediated by OH derived from the copper-catalyzed Fenton-like reaction. Incubation of hydroxyurea and Cu,Zn-SOD with xanthine oxidase and hypoxanthine in a system forming O2- -->H2O2 also resulted in appreciable NO production. These results suggest that NO production from hydroxyurea catalyzed by copper-containing proteins may be the molecular basis of the pharmacological and antitumor action of hydroxyurea.
 ...
PMID:Nitric oxide generation from hydroxyurea via copper-catalyzed peroxidation and implications for pharmacological actions of hydroxyurea. 947 38

Oil emulsion and raw and cooked tissue homogenates were used to determine the mechanisms of various iron forms on the catalysis of lipid peroxidation. Flax oil (0.25 g) was blended with 160 mL maleate buffer (0.1 M, pH 6.5) to prepare an oil emulsion. Raw or cooked turkey leg meat was used to prepare meat homogenates. Samples were prepared by adding iron from each of the various sources, reactive oxygen species, or enzyme (xanthine oxidase and superoxide dismutase) systems into the oil emulsion or meat homogenates. In oil emulsion and cooked-meat homogenates, ferrous iron and hemoglobin had strong prooxidant effects, but ferritin became prooxidant only when ascorbate was present. Hemoglobin and ferritin had no prooxidant effect in raw-meat homogenates. The status of heme iron and the released iron from hemoglobin had little effect on the prooxidant effect of hemoglobin in oil emulsion and cooked meat homogenate systems. The prooxidant effect of ferrous iron in oil emulsion and cooked-meat homogenates disappeared in the presence of superoxide (.O2-), H2O2, or xanthine oxidase systems. In raw-meat homogenates, however, ferrous had strong prooxidant effects even in the presence of .O2-, or H2O2. The status of free iron was the most important factor in the oxidation of oil emulsion and cooked-meat homogenates but the impact in raw-meat homogenates was small.
 ...
PMID:Prooxidant effects of ferrous iron, hemoglobin, and ferritin in oil emulsion and cooked-meat homogenates are different from those in raw-meat homogenates. 949 4


<< Previous 1 2 3 4 5 6 7 Next >>