Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Reduced oxygen intermediates have been shown to directly depress cardiac muscle function at the subcellular, tissue, and whole animal levels. The exact species of reduced oxygen intermediate [superoxide anion radical (O2-.), H2O2, hydroxyl free radical (HO.)] and the concentrations necessary to depress cardiac muscle function have not been quantified. To better understand the role of O2-. and H2O2, we have studied rabbit right ventricular papillary muscle function in the presence of these reduced oxygen intermediates generated by a xanthine-xanthine oxidase system at 37 degrees C. In the presence of xanthine (0.1 mM) and xanthine oxidase (0.02 U/ml), 57.5 +/- 0.85 nmol.l-1.s-1 O2-. and 69.25 +/- 5.3 nmol.l-1.s-1 H2O2 were produced. In the presence of superoxide dismutase (SOD), O2-. was eliminated and H2O2 concentration increased. Catalase effectively eliminated the accumulation of H2O2 without significantly changing the rate of O2-. generation. When applied to isometrically contracting right ventricular papillary muscles, this system, with or without SOD and catalase, had no effect on peak developed tension or +/- dT/dt derived either from length-tension or force-frequency studies. However, when the xanthine oxidase concentration was increased to 0.112 U/ml, the rate of O2-. generation increased to 196.67 +/- 3.26 nmol.l-1.s-1 and H2O2 production increased to 142.19 +/- 9.3 nmol.l-1.s-1 with significant depression of papillary muscle tension development. SOD virtually eliminated O2-. production, whereas H2O2 production increased to 199.48 +/- 9.8 nmol.l-1.s-1 with no effect on papillary muscle tension development.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitative identification of superoxide anion as a negative inotropic species. 283 94

It has been postulated that changes in the availability of partially reduced O2 species, such as O2 radicals, could serve as a link between PO2 in the alveolus and pulmonary vascular tone (Herz 11: 127-141, 1986). To assess this hypothesis, the hemodynamic effects of acute changes in the balance between the production of O2 radicals and availability of antioxidant enzymes were studied in the isolated perfused rat lung. Intravascular generation of O2 radicals, by administration of xanthine-xanthine oxidase, decreased the pulmonary vascular pressor response to alveolar hypoxia (-55 +/- 5%) and angiotensin II (-58 +/- 10%, P less than 0.01 for each) in isolated perfused rat lungs without increasing the lung wet-to-dry weight ratio. Decreases in pulmonary vascular reactivity were inhibited by pretreatment of the lung with desferrioxamine or a mixture of catalase and superoxide dismutase. Catalase and superoxide dismutase preserved the hypoxic pressor response whether given in liposomes or in dissolved form. Superoxide dismutase administered free in solution, or combined with catalase in liposomes, increased the normoxic pulmonary arterial pressure and enhanced vascular reactivity to angiotensin II and hypoxia. Lungs treated with antioxidant enzymes in liposomes had 50% higher lung catalase levels than control lungs (P less than 0.05). These findings demonstrate that exogenous partially reduced O2 species can decrease pulmonary vascular reactivity and suggest that endogenous radicals, superoxide radical in particular, might be important in modulating pulmonary vascular tone.
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PMID:Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung. 291 13

Ferritin was found to promote the peroxidation of phospholipid liposomes, as evidenced by malondialdehyde formation, when incubated with xanthine oxidase, xanthine, and ADP. Activity was inhibited by superoxide dismutase but markedly stimulated by the addition of catalase. Xanthine oxidase-dependent iron release from ferritin, measured spectrophotometrically using the ferrous iron chelator 2,2'-dipyridyl, was also inhibited by superoxide dismutase, suggesting that superoxide can mediate the reductive release of iron from ferritin. Potassium superoxide in crown ether also promoted superoxide dismutase-inhibitable release of iron from ferritin. Catalase had little effect on the rate of iron release from ferritin; thus hydrogen peroxide appears to inhibit lipid peroxidation by preventing the formation of an initiating species rather than by inhibiting iron release from ferritin. EPR spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide was used to observe free radical production in this system. Addition of ferritin to the xanthine oxidase system resulted in loss of the superoxide spin trap adduct suggesting an interaction between superoxide and ferritin. The resultant spectrum was that of a hydroxyl radical spin trap adduct which was abolished by the addition of catalase. These data suggest that ferritin may function in vivo as a source of iron for promotion of superoxide-dependent lipid peroxidation. Stimulation of lipid peroxidation but inhibition of hydroxyl radical formation by catalase suggests that, in this system, initiation is not via an iron-catalyzed Haber-Weiss reaction.
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PMID:Ferritin and superoxide-dependent lipid peroxidation. 298 54

The reactive species involved in the cell lysis during ultraviolet irradiation of Ehrlich ascitic carcinoma cells in the presence of red hair melanin (RHM) were investigated by determining 51Cr release from labeled cells. Cysteine at 1 mM in the presence of RHM increased the cell lysis during the incubation in the dark as well as during irradiation; this lysis was enhanced by superoxide dismutase (SOD). Catalase abolished the dark reaction and inhibited the cysteine-induced increase of cell lysis during irradiation. The cell lysis by the superoxide-generating xanthine oxidase system was not significantly increased by SOD, but was significantly decreased by nitroblue tetrazolium and completely abolished by catalase. The cell lysis induced by the supernatants obtained from the suspensions of RHM either irradiated alone or with cysteine was abolished by catalase. Sediments of irradiated RHM when incubated in the dark with the cells did not release 51Cr. Irradiation of the cells in the presence of the same sediments produced lysis which was not inhibited by catalase. These studies suggest that superoxide per se is not toxic to the cells, but the H2O2 formed by dismutation of superoxide produces cell lysis either directly or by generating OH through Fenton-type reactions. A large part of the cell lysis seen during irradiation of cells in the presence of RHM is not due to H2O2, but may possibly be due to the melanin free radicals formed during irradiation.
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PMID:Role of superoxide and hydrogen peroxide in cell lysis during irradiation in vitro of Ehrlich ascitic carcinoma cells in the presence of melanin. 299 Jun 46

The role of oxygen-derived free radicals (ODFR) in lectin-dependent cellular cytotoxicity (LDCC) in humans was investigated. The hydroxyl radical traps thiourea, methanol, ethanol and phenol were effective in inhibiting LDCC, as was DABCO, a singlet oxygen quencher. The proposed pathway of hydroxyl radical production in living cells is either an iron catalysed Haber-Weiss reaction or a Fenton reaction. The effect of inhibitors of these pathways was investigated. The superoxide anion scavengers superoxide dismutase, ferricytochrome c and Tiron were without effect. It was shown that Tiron inhibits the lucigenin-amplified chemiluminescence produced by the action of xanthine oxidase, and also the lucigenin-amplified chemiluminescence produced by activated PMN, suggesting that this agent (Tiron) scavenges intracellular superoxide anion. Catalase gave slight inhibition of LDCC only. The ferric iron chelator desferrioxamine gave no protection of the target cells, while the ferrous chelator, 1,10-phenanthroline, inhibited LDCC and partially prevented the detection of hydroxyl radicals generated by the Fe2+-H2O2 system. Cibacron blue, an agent that inhibits NAD(P)H linked enzymes, also inhibited LDCC. The cyclo-oxygenase inhibitors indomethacin and salicylate were without effect, while the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) inhibited cytolysis. None of the LDCC inhibitors was cytotoxic to the effector cells or to the target cells, neither did they inhibit lymphocyte-target binding. The findings would suggest that hydroxyl radicals have a role to play in human T-cell mediated cytolysis, either as the active lytic agent or as an epiphenomenon.
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PMID:Hydroxyl radical scavengers inhibit human lectin-dependent cellular cytotoxicity. 301 54

Culture medium of lymphocyte cultures that have been exposed to the superoxide generating system hypoxanthine plus xanthine oxidase (X-XO) contains substances with chromosome damaging properties. This is demonstrated by the ability of ultrafiltrates of such culture media to induce chromosomal aberrations and sister chromatid exchanges in the lymphocytes of blood test cultures. Culture medium becomes active about 15 hours after the addition of X-XO and stimulation by phytohemagglutinin. Concomitant with the accumulation of clastogenic material, assays for conjugated dienes and thiobarbituric acid-reactive material which measure lipid-peroxidation become positive in the culture media. When cells are pretreated with superoxide dismutase or glutathione peroxidase before the addition of X-XO neither clastogenic substances nor lipid peroxidation products are detected. Catalase is a less efficient protector.
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PMID:Treatment of lymphocyte cultures with a hypoxanthine-xanthine oxidase system induces the formation of transferable clastogenic material. 301 71

A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radical may mediate the mucosal injury produced by reperfusion of ischemic intestine. Xanthine oxidase has been proposed as the primary source of these reduced O2 species because pretreatment with xanthine oxidase inhibitors such as allopurinol or pterin aldehyde prevent postischemic mucosal injury. Another potential source of oxygen radicals is the inflammatory neutrophil. To ascertain whether neutrophils could play a role in the pathogenesis of ischemia-reperfusion injury in the small bowel we examined the effect of ischemia and reperfusion on neutrophil infiltration and tissue levels of reduced glutathione, superoxide dismutase, and catalase. Our studies demonstrate that reperfusion of ischemic intestines results in a dramatic increase (1,800%) in neutrophil infiltration and a concurrent loss of reduced glutathione and superoxide dismutase of 60 and 30%, respectively. Catalase activity was unaffected by ischemia-reperfusion. Pretreatment with allopurinol or administration of superoxide dismutase prevented the influx of neutrophils and retarded the drop in reduced glutathione levels. These results suggest a relationship among xanthine oxidase-generated oxy radicals, neutrophil extravasation, and mucosal damage. We propose that ischemia and reperfusion results in xanthine oxidase-generated, superoxide-dependent accumulation of inflammatory neutrophils in the mucosa where neutrophil-derived reactive oxygen metabolites mediate and/or exacerbate intestinal injury.
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PMID:Xanthine oxidase and neutrophil infiltration in intestinal ischemia. 302 Sep 94

The potential for iron bound to transferrin to be released and promote the peroxidation of phospholipid liposomes was investigated using ADP as a low molecular weight chelator and superoxide generated by the xanthine/xanthine oxidase system as the reducing agent. Lipid peroxidation in this system was dependent upon transferrin as the source of iron; increasing the transferrin concentration resulted in increased rates of lipid peroxidation. Increasing the xanthine oxidase activity also caused increased rates of peroxidation. Catalase stimulated rates of peroxidation at all xanthine oxidase activities tested. Conditions resulting in the most rapid release of iron from transferrin (low pH, high ADP) did not promote the greatest rates of lipid peroxidation, indicating that at neutral pH, rates of lipid peroxidation may be limited by the availability of iron. It is concluded that transferrin is not a likely source of iron for catalysis of deleterious biological oxidations such as lipid peroxidation in vivo.
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PMID:Transferrin-dependent lipid peroxidation. 302 12

Oxidant injury to the alveolar epithelium can be mediated by exposure to oxidant gases such as O2 at high concentrations and O3, inflammatory cell-derived reactive O2 species, and the intracellular metabolism of xenobiotics such as paraquat. An in vitro model of alveolar epithelial oxidant injury was developed based on exposure of cultured rat type II pneumocytes to superoxide and hydrogen peroxide (H2O2) enzymatically generated in the culture medium. Cytotoxicity was assessed by the release of lactate dehydrogenase (LDH) into the culture medium, which was a more reliable indicator of damage than release of 51Cr by prelabeled cells. Incubation of cells for 6-8 h with xanthine plus xanthine oxidase and glucose plus glucose oxidase induced the release of greater than 50% of total intracellular LDH. Oxidant exposure also resulted in significant detachment of cells from culture dishes. Modulation of oxidant damage was accomplished using liposomes as vectors for the delivery of catalase. Treatment of cells with catalase liposomes for 2 h resulted in augmentation of cellular catalase specific activities up to 631% of controls. Catalase was partitioned into intracellular and surface-associated compartments in catalase liposome-treated cells. Partial and complete protection against oxidant injury, induced by xanthine plus xanthine oxidase and glucose plus glucose oxidase, respectively, was achieved by pretreatment of cells with catalase liposomes. LDH release during oxidant exposure was inversely related to augmentation of cellular catalase activities. Catalase liposome-treated cells also exhibited an enhanced ability to scavenge enzymatically generated H2O2 from the culture medium. These observations suggest a useful approach to modulation of alveolar injury induced by reactive O2 species.
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PMID:Liposome-mediated augmentation of catalase in alveolar type II cells protects against H2O2 injury. 304 Jun 61

Reactive oxygen metabolites have been reported to be responsible for the pathogenesis of ischemia-induced gastric mucosal lesions. We have investigated the possible protective effect of specific enzymes and oxygen radical scavenging agents on oxygen metabolite-induced injury to cultured gastric mucosal cells. Oxygen-reactive metabolites were generated by 1 mM xanthine and 10-100 mU/ml xanthine oxidase. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells. Xanthine oxidase caused a dose-dependent increase of 51Cr release in the presence of 1 mM xanthine. Catalase (an enzyme that reduces hydrogen peroxide) diminished xanthine-xanthine oxidase-induced 51Cr release in a dose-dependent manner. Superoxide dismutase (a scavenger of superoxide radical) failed to affect the amounts of 51Cr release induced by xanthine plus xanthine oxidase. Pretreatment with diethyl maleate, which depletes intracellular glutathione, potentiated oxygen radical-mediated 51Cr release dose dependently. The presence of ferrous ion or ethylenediaminetetraacetic acid-chelated iron, which promote the formation of hydroxyl radical, did not alter xanthine-xanthine oxidase-induced cellular injury. Furthermore, agents that inactivate hydroxyl radical also failed to protect the cells from oxygen metabolite-induced injury. We conclude that in vitro oxygen metabolites, extracellularly generated, have a direct toxic effect on gastric mucosal cells; hydrogen peroxide is a major mediator of oxygen metabolite-induced gastric cell injury; the oxygen-derived superoxide and hydroxyl radicals are less toxic to gastric mucosal cells than hydrogen peroxide; and intracellular glutathione, which detoxifies hydrogen peroxide, may be involved in antioxidant defense mechanisms.
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PMID:Oxygen metabolite-induced cytotoxicity to cultured rat gastric mucosal cells. 311 Dec 74


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