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)

Dissemination of Leishmania within the host is related to parasites undergoing unchecked proliferation. We therefore studied the effects of oxidant generating systems on promastigote multiplication by (i) direct determinations of organism proliferation and (ii) the incorporation of [3H]uracil into promastigote nucleoprotein. These two parameters correlated closely as measures of organism replication as demonstrated by parallel suppression of them by the protein synthesis inhibitors puromycin and cycloheximide and the nucleic acid synthesis inhibitors actinomycin D and mitomycin C. Promastigotes showed dose-related susceptibility to reagent and generated hydrogen peroxide (H2O2) as reflected in quantitatively similar decreases in multiplication and [3H]uracil incorporation. These effects were specific for H2O2 as catalase abrogated the dimunition in multiplication. The generation of superoxide anion by acetaldehyde-xanthine oxidase (10 mU/ml) did not alter promastigote replication or nucleoprotein synthesis. These results indicate that Leishmania donovani promastigotes are damaged by H2O2 and that the incorporation of [3H]uracil into promastigote nucleoprotein may be useful for studying the interaction of this parasite with host effector cells.
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PMID:Oxidant-mediated damage of Leishmania donovani promastigotes. 628 40

Our previous studies established that human neutrophils could damage and probably kill hyphae of Aspergillus fumigatus and Rhizopus oryzae in vitro, primarily by oxygen-dependent mechanisms active at the cell surface. These studies were extended, again quantitating hyphal damage by reduction in uptake of (14)C-labeled uracil or glutamine. Neither A. fumigatus nor R. oryzae hyphae were damaged by neutrophils from patients with chronic granulomatous disease, confirming the importance of oxidative mechanisms in damage to hyphae. In contrast, neutrophils from one patient with hereditary myeloperoxidase deficiency damaged R. oryzae but not A. fumigatus hyphae. Cell-free, in vitro systems were then used to help determine the relative importance of several potentially fungicidal products of neutrophils. Both A. fumigatus and R. oryzae hyphae were damaged by the myeloperoxidase-hydrogen peroxide-halide system either with reagent hydrogen peroxide or enzymatic systems for generating hydrogen peroxide (glucose oxidase with glucose, or xanthine oxidase with either hypoxanthine or acetaldehyde). Iodide with or without chloride supported the reaction, but damage was less with chloride alone as the halide cofactor. Hydrogen peroxide alone damaged hyphae only in concentrations >/=1 mM, but 0.01 mM hypochlorous acid, a potential product of the myeloperoxidase system, significantly damaged R. oryzae hyphae (a 1 mM concentration was required for significant damage to A. fumigatus hyphae). Damage to hyphae by the myeloperoxidase system was inhibited by azide, cyanide, catalase, histidine, and tryptophan, but not by superoxide dismutase, dimethyl sulfoxide, or mannitol. Photoactivation of the dye rose bengal resulted in hyphal damage which was inhibited by histidine, tryptophan, and 1,4-diazobicyclo(2,2,2)octane. Lysates of neutrophils or separated neutrophil granules did not affect A. fumigatus hyphae, but did damage R. oryzae hyphae. Similarly, three preparations of cationic proteins purified from human neutrophil granules were more active in damaging R. oryzae than A. fumigatus hyphae. This damage, as with the separated granules and whole cell lysates, was inhibited by the polyanion heparin. Damage to R. oryzae hyphae by neutrophil cationic proteins was enhanced by activity of the complete myeloperoxidase system or by hydrogen peroxide alone in subinhibitory concentrations. These data support the importance of oxidative products in general and the myeloperoxidase system in particular in damage to hyphae by neutrophils. Cationic proteins may also contribute significantly to neutrophil-mediated damage to R. oryzae hyphae.
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PMID:Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro. 629 3

Leukotriene B4 chemotactic activity and leukotriene C4, D4 and E4 slow reacting substance activity were rapidly decreased by hydroxyl radicals generated by two different iron-supplemented acetaldehyde-xanthine oxidase systems. At low Fe2+, leukotriene inactivation was inhibited by catalase, superoxide dismutase, mannitol and ethanol, suggesting involvement of hydroxyl radicals generated by the iron-catalyzed interaction of superoxide and H2O2 (Haber-Weiss reaction). Leukotriene inactivation increased at high Fe2+ concentrations, but was no longer inhibitable by superoxide dismutase, suggesting that inactivation resulted from a direct interaction between H2O2 and Fe2+ to form hydroxyl radicals (Fenton reaction). The inactivation of leukotrienes by hydroxyl radicals suggests that oxygen metabolites generated by phagocytes may play a role in modulating leukotriene activity.
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PMID:Leukotriene B4, C4, D4 and E4 inactivation by hydroxyl radicals. 630 43

Mouse pial arterioles were exposed to the free radical-generating reactants acetaldehyde and xanthine oxidase. Concentrations of 0.5 mM acetaldehyde and 0.1 U/ml xanthine oxidase caused reversible dilations, whereas higher concentrations produced initial constrictions followed by reversible dilations. The following free radical scavengers inhibited the dilation when added to the lower concentrations of reactants: superoxide dismutase, a superoxide scavenger; catalase, an H2O2 scavenger; and mannitol, a hydroxyl scavenger. In addition, pretreatment of the animal with dimethyl sulfoxide, a hydroxyl scavenger, also inhibited the response. The scavengers were also tested against either the dilation produced by increased inspired CO2 or against the dilation produced by local application of 10(-3) M papaverine. No significant effect was observed. The data support the hypothesis that hydroxyl radicals can dilate pial arterioles, since all the scavengers can ultimately reduce levels of hydroxyl generated by acetaldehyde plus xanthine oxidase.
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PMID:Effects of free radical generation on mouse pial arterioles: probable role of hydroxyl radicals. 630 66

Appropriately stimulated neutrophils release peroxidase and undergo a respiratory burst to form hydrogen peroxide (H2O2) and hydroxyl radicals (OH). We report here that both the myeloperoxidase-H2O2-halide system and OH released in this way can degrade the leukotrienes (LT) formed by neutrophils. More LTB4 and LTC4 were recovered from the supernatants of chronic granulomatous disease neutrophils (which are unable to respond to stimulation with a respiratory burst) than from normal or myeloperoxidase-deficient neutrophils when stimulated with the calcium ionophore A23187. When radiolabeled LTC4 was added, 72% of the LTC4 was recovered from the chronic granulomatous disease cells in contrast to 0% from the myeloperoxidase-deficient and normal cells. Inhibitor studies using catalase, superoxide dismutase, azide, mannitol, or ethanol suggested that LTC4 degradation was mediated primarily by the myeloperoxidase system in normal cells and by OH in myeloperoxidase-deficient cells. LTC4 degradation by the cell-free myeloperoxidase-H2O2-halide system and the OH -generating acetaldehyde-xanthine oxidase-Fe2+ system had inhibitor profiles comparable to normal and myeloperoxidase-deficient neutrophils, respectively. LTC4 degradation products formed by the stimulated neutrophils and model systems included the 5-(S), 12-(R)- and 5-(S), 12-(S)-6-trans-isomers of LTB4. Thus phagocytes may modulate LT activity in inflammatory sites by the inactivation of these potent biologic mediators by at least two oxidative mechanisms.
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PMID:Leukotriene production and inactivation by normal, chronic granulomatous disease and myeloperoxidase-deficient neutrophils. 631

The reaction of superoxide with reduced glutathione (GSH) was studied with two O-.2-producing systems: xanthine oxidase using xanthine or acetaldehyde as substrates, and secondly, quinol autoxidation. The capability of GSH to quench superoxide radicals was detected by lowered O-.2-mediated cytochrome c3+ reduction. The formation of the oxidation products, glutathione disulfide (GSSG) and glutathione sulfonate (the latter at levels of about 6-15% compared to GSSG), was dependent on the O-.2 production and was inhibited by superoxide dismutase. The presence of GSH together with an O-.2-producing system led to an extra uptake of oxygen, which was also depressed by superoxide dismutase. The observed O2 uptake was accounted for by the formation of GSSG and GSO-3 from GSH; the data are in accordance with a mechanism involving thiyl radicals. Low-level chemiluminescence measurement indicated the formation of excited oxygen species. The intensity of photoemission was dependent on the GSH concentration and on the O-.2 production rate. Chemiluminescence was inhibited by superoxide dismutase and also by glutathione peroxidase, but not by catalase or OH. quenchers. Spectral analysis and the effects of 1,4-diazabicyclo[2.2.2]octane and sodium azide indicated the contribution of singlet molecular oxygen to the light emission. It is suggested that singlet oxygen results from an intermediate oxygen addition product such as a glutathione peroxysulphenyl radical.
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PMID:Oxidation of glutathione by the superoxide radical to the disulfide and the sulfonate yielding singlet oxygen. 631 88

Treatment of human neutrophils with triphenyltin chloride (TPTCl)-inhibited superoxide (O-2) production stimulated with phorbol myristate acetate (PMA). TPTCl was more potent as inhibitor of O-2 production than other phenyltin compounds. The O-2 production by the xanthine oxidase-acetaldehyde system was not inhibited by TPTCl. This finding indicates that TPTCl does not itself react with O-2. Furthermore, TPTCl did not influence the isolated NADPH oxidase at all, though O-2 production of neutrophils stimulated with PMA in the presence of TPTCl was inhibited. These results indicate that TPTCl inhibits the activation process of the O-2 generating system.
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PMID:Triphenyltin chloride inhibits superoxide production by human neutrophils stimulated with a surface active agent. 631 50

Treatment of rabbit polymorphonuclear leukocytes (PMN) with triphenyltin chloride (TPTCl) inhibited chemiluminescence generation stimulated by particulate stimulus, zymosan, or soluble stimuli, concanavalin A + cytochalasin D. Superoxide anion (O-2) production was also inhibited, indicating that the inhibition involved inhibition of early oxidative metabolic process(es). The direct inhibition of the activation process of the oxidative burst was established by the experiments showing that a) chemiluminescence generated by xanthine oxidase-acetaldehyde system was not inhibited by TPTCl, b) washing the PMN after the treatment with TPTCl did not affect the results of chemiluminescence, and c) there was no change in cell viability after the treatment with TPTCl.
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PMID:Inhibition of oxidative metabolism in rabbit polymorphonuclear leukocytes by triphenyltin chloride. 631 89

Sickle cell anemia and other chronic hemolytic anemias are associated with an increased frequency of bacterial infections. There is evidence to suggest that in hemolytic states massive erythrocyte (RBC) ingestion by macrophages interferes with their antibacterial function, thereby predisposing infection. Stimulated by this possibility, we recently demonstrated that erythrophagocytosis by macrophages markedly inhibited intracellular killing of bacteria, and that zymosan-stimulated superoxide generation and chemiluminescence were also suppressed by RBC ingestion. We examined the effects of RBC components on generation of chemiluminescence, superoxide, and bactericidal activity by cell-free oxidative systems. Generation of chemiluminescence by hypoxanthine-xanthine oxidase was depressed in the presence of human RBC lysate or column-fractionated hemoglobin but not crystallized human hemoglobin (methemoglobin) (peak cpms of 15,522 [P = 0.00024], 28,360 [P = 0.0088], and 50,041 [P = 0.37], respectively, compared with 59,898 for positive controls). Similarly, hypoxanthine-xanthine oxidase production of superoxide was inhibited in the presence of column-fractionated human hemoglobin (43.8 versus 17.4 nmol per tube, P = 0.000001). A cell-free bactericidal system, acetaldehyde and xanthine oxidase with or without myeloperoxidase and Cl-, was markedly inhibited by column-purified hemoglobin. For example, after 2 h of incubation, surviving numbers of Staphylococcus aureus were: control (buffer only), 2.5 X 10(6)/ml; bactericidal system, none; bactericidal system plus hemoglobin, 2.2 X 10(6)/ml (P less than or equal to 0.03, bactericidal system versus other systems). Our studies have documented that interactions between RBC (hemoglobin) and reactive products of oxygen metabolism inhibit oxidative bactericidal mechanisms in cell-free systems as well as in macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of cell-free oxidative bactericidal activity by erythrocytes and hemoglobin. 632 49

DMSO is a hydroxyl radical scavenger that inhibits platelet aggregation in vivo in injured microvessels, and that also inhibits the dilation displayed by pial arterioles following a local injury. The injurious stimulus is a result of local excitation of circulating sodium fluorescein by an appropriate light source. It is likely that this excitation results in the generation of hydroxyl radicals, which are the immediately injurious agent. This postulate is supported not only by the inhibitory effect of DMSO but also by the inhibitory effect of glycerol, another hydroxyl scavenger. Both the hypothesis that DMSO inhibits hydroxyl-mediated dilation, and the hypothesis that free radicals can dilate pial arterioles, are further supported by direct evidence from studies employing local application of xanthine oxidase plus acetaldehyde. This well established radical-generating system dilated pial arterioles. The dilation was inhibited by the local application of superoxide dismutase and also by local application of catalase, as well as by intraperitoneal administration of DMSO. Since DMSO failed to inhibit the dilation produced by increases of inspired CO2, we believe that the inhibitory effect of DMSO on the other dilating stimuli in these studies was due to the hydroxyl scavenging properties of this drug, rather than to other nonspecific effects.
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PMID:Dimethyl sulfoxide effects on platelet aggregation and vascular reactivity in pial microcirculation. 641 Sep 63


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