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 biliary GSSG efflux rate of normoxic perfused rat liver was 1.5 +/- 0.2 nmol/min/g liver wet weight. The GSSG efflux rate as indicator for the flux through the glutathione peroxidase reaction and, therefore, for an oxidative loading increased with the extent of hypoxia. 2.6 +/- 0.5 nmol/min/g were released from the severely hypoxic liver. The hydroxyl radical scavenger formate as well as the xanthine oxidase inhibitor allopurinol reduced the efflux rate of GSSG. GSH was released from the perfused liver at a rate of 15.5 nmol/min/g which was nearly unchanged in severe hypoxia. The high rate of glucose liberation from the hypoxic liver declined to almost that of the normoxic organ in the presence of formate. There is an 'oxidative stress' during hypoxic liver perfusion which probably originates from increased generation of activated oxygen species in the degradation of purine nucleotides.
 ...
PMID:Formation of activated oxygen in the hypoxic rat liver. 383 24

Primary cultures of porcine aortic endothelial cells were used to assess the effects of O2 intermediates produced by 10-40 mU/ml xanthine oxidase (XO; +2 mM hypoxanthine) or 25-100 mU/ml glucose oxidase (GO; +5 mM glucose). A 60-min incubation in the presence of the enzyme systems resulted in a dose-dependent toxic effect with evidence of cytolysis (increased LDH release) and cell loss (decrease in DNA and protein content), when these indexes were measured 24 hr after completion of the enzyme reaction. Decreased [3H]thymidine incorporation into DNA was the most sensitive index of cell dysfunction for both enzyme systems. The effects of various scavengers and enzymes indicated that H2O2 was the main O2 intermediate involved in the cytotoxicity resulting from the XO-hypoxanthine reaction. Increased glutathione peroxidase activity associated with the addition of 2 X 10(-7) M selenomethionine to culture medium had a partial protective effect which could be related to an increased rate of H2O2 degradation. Evidence for increased DNA synthesis after injury was found in cells previously exposed to XO-hypoxanthine, the degree of increase in [3H]thymidine incorporation being dependent on the intensity of the initial cytotoxicity. Cultured endothelial cells provide a useful tool to evaluate the role of O2 intermediates in endothelial cell injury, to test the effects of protective agents, and to study the repair process.
 ...
PMID:Effect of variable glutathione peroxidase activity on H2O2-related cytotoxicity in cultured aortic endothelial cells. 383 24

There is evidence that oxygen-derived free radicals may play a role in myocardial ischaemic and reperfusion injury. Major sources of O2 free radicals formation during ischaemia and reperfusion are: the enzyme xanthine oxidase, activated neutrophils and the myocardial mitochondria. However, in the heart there are defense mechanisms against the toxic oxygen metabolites. They include the enzyme superoxide dismutase, catalase and glutathione peroxidase plus endogenous antioxidants like vitamin E, ascorbic acid and cysteine. We have investigated in the isolated rabbit hearts the effects of ischaemia and reperfusion on these defence mechanisms. 90 min of ischaemia and/or hypoxia induced a significant reduction of mitochondrial superoxide dismutase, and of reduced glutathione/oxidized glutathione ratio which was further declined after reperfusion indicating that an oxidative stress has occurred. These alterations are associated with massive tissue and mitochondrial calcium accumulation, loss of mitochondrial function and severe membrane damage. The effects of vitamin E on these parameters have been investigated. Administration of 1.1 mg of dl-alpha-tocopherol acetate showed a protective effect on mitochondrial function but it failed to improve the recovery of mechanical function during reperfusion.
 ...
PMID:Role of oxygen in myocardial ischaemic and reperfusion damage: effect of alpha-tocopherol. 384 29

1. The aerobic loss of GSH added to the supernatant fraction from rat liver is much increased by including the microsome fraction, which both inhibits the concurrent reduction of the GSSG formed and also augments the net oxidation rate. 2. Oxidation occurs with a mixture of dialysed supernatant and a protein-free filtrate; the latter is replaceable by hypoxanthine and the former by xanthine oxidase, whereas fractions lacking this enzyme give no oxidation. 3. In all these instances augmentation occurs with microsomes, with fractions having urate oxidase activity and with the purified enzyme; uric acid and microsomes alone also support the oxidation. 4. Evidence implicating additional protein factors is discussed. 5. It is suggested that GSH oxidation by homogenate is linked through glutathione peroxidase to the reaction of endogenous substrate with supernatant xanthine oxidase and of the uric acid formed with peroxisomal urate oxidase.
 ...
PMID:The function of subcellular fractions in the oxidation of glutathione in rat liver homogenate. 545 15

To explore the susceptibility of the extracellular protozoan, Entamoeba histolytica, to toxic oxygen intermediates, trophozoites were exposed to fluxes of O2, H2O2, and OH. generated enzymatically by the glucose oxidase and xanthine oxidase reactions. HM-1 trophozoites were resistant to O2, but were readily killed by H2O2 alone. OH. and 1O2 were not required for effective amebicidal activity. The addition of peroxidase and halide enhanced trophozoite killing by H2O2. Sonicates of amebae contained virtually no catalase and little glutathione peroxidase activity which may contribute to susceptibility to H2O2. Coupled with our previous studies with Toxoplasma gondii and Leishmania spp. these observations indicate that there is a broad spectrum of susceptibility of intra- and extracellular pathogenic protozoa to killing by oxygen intermediates.
 ...
PMID:Susceptibility of Entamoeba histolytica to oxygen intermediates. 627 8

This investigation examined the effect of the anthracycline antitumor agents on reactive oxygen metabolism in rat heart. Oxygen radical production by doxorubicin, daunorubicin, and various anthracycline analogues was determined in heart homogenate, sarcoplasmic reticulum, mitochondria, and cytosol, the major sites of cardiac damage by the anthracycline drugs. Superoxide production in heart sarcosomes was significantly increased by anthracycline treatment; for doxorubicin, the reaction appeared to follow saturation kinetics with an apparent Km of 112.62 microM, required NADPH as cofactor, was accompanied by the accumulation of hydrogen peroxide, and probably resulted from the transfer of electrons to molecular oxygen by the doxorubicin semiquinone after reduction of the drug by sarcosomal NADPH:cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4). Superoxide formation was also significantly enhanced by the anthracycline antibiotics in the mitochondrial fraction. Doxorubicin stimulated mitochondrial superoxide formation in a dose-dependent manner that also appeared to follow saturation kinetics (apparent Km of 454.55 microM); however, drug-related superoxide production by mitochondria required NADH rather than NADPH and was significantly increased in the presence of rotenone, which suggested that the proximal portion of the mitochondrial NADH dehydrogenase complex [NADH:(acceptor) oxidoreductase, EC 1.6.99.3] was responsible for the reduction of doxorubicin at this site. In heart cytosol, anthracycline-induced superoxide formation and oxygen consumption required NADH and were significantly reduced by allopurinol, a potent inhibitor of xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2). Reactive oxygen production was detected in all of our studies despite the presence of both superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and glutathione peroxidase (glutathione:hydrogen peroxide oxidoreductase, EC 1.11.1.9) in each cardiac fraction. These results suggest that free radical formation by the anthracycline antitumor agents, which occurs in the same myocardial compartments that are subject to drug-induced tissue injury, may damage the heart by exceeding the oxygen radical detoxifying capacity of cardiac mitochondria and sarcoplasmic reticulum.
 ...
PMID:Effect of anthracycline antibiotics on oxygen radical formation in rat heart. 629 97

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.
 ...
PMID:Oxidation of glutathione by the superoxide radical to the disulfide and the sulfonate yielding singlet oxygen. 631 88

Thromboxane B2 biosynthesis from arachidonic acid was increased in platelets from hypercholesterolemic rabbits. The enzymic activity of phospholipase A2 which releases arachidonic acid, the precursor for the biosynthesis of thromboxane B2, showed hardly any change in hypercholesterolemic platelets. Phospholipase C and diglyceride lipase activities also were not changed in platelets from hypercholesterolemic rabbits. Furthermore, phospholipid concentration in platelets were not increased in this state. Thus, I conclude that the supply of precursor for thromboxane B2 biosynthesis was not increased in platelets from hypercholesterolemic rabbits as compared to controls. I have clarified this mechanism for the increased thromboxane synthesis. The biosynthesis of prostaglandin H2 and thromboxane B2 were unaffected by superoxide dismutase, xanthine, xanthine oxidase, mannitol, or benzoate in the experiments designed to study the possible involvement of reactive oxygen species. The effect of glutathione, glutathione peroxidase and H2O2 on cyclooxygenase and thromboxane synthetase were studied by using partially purified enzymes and platelet microsomes. Glutathione and glutathione peroxidase inhibited the activity of the cyclooxygenase but did not inhibit that of thromboxane synthetase. H2O2 caused the inactivation of cyclooxygenase, but the addition of H2O2 did not inhibit the formation of thromboxane B2 from prostaglandin H2. An examination of glutathione concentration and glutathione peroxidase activity in platelets from normal and experimentally hypercholesterolemic rabbits demonstrated that both were decreased in platelets from latter group. The observed alterations in glutathione levels and glutathione peroxidase activity are large enough to cause increased thromboxane B2 synthesis in platelets but the possibility that other unidentified factors may also contribute cannot be excluded.
 ...
PMID:Thromboxane synthesis in hypercholesterolemic platelets--on the mechanism of increased thromboxane synthesis. 661 25

In order to understand why different stages of Trichinella spiralis vary in their susceptibility to killing by leukocytes, the effects of artificially generated oxidants on different stages of this parasite were compared. More than 90% newborn larvae were killed after incubation in acetaldehyde-xanthine oxidase or glucose-glucose oxidase. On the other hand, fewer than 10% of adult worms or muscle larvae were killed when incubated under identical conditions. Thus, only the stages which are resistant to killing by leukocytes are resistant to killing by oxidants. The larvicidal effect of acetaldehyde-xanthine oxidase was blocked by the addition of either superoxide dismutase or catalase and was partially inhibited by radical scavengers and singlet oxygen quenchers. The oxidant resistant adults and muscle larvae contained 3-5 times more superoxide dismutase and at least five times more glutathione peroxidase than the oxidant sensitive newborn larvae. In contrast, all 3 stages lacked detectable amounts of catalase and contained roughly equivalent amounts of reduced glutathione. Accordingly, adults and muscle larvae may be more resistant to killing by leukocytes than newborn larvae because they contain better oxidant defenses.
 ...
PMID:Scavenger enzymes and resistance to oxygen mediated damage in Trichinella spiralis. 669 69

Erythrocytes from young and old rats were separated into four age fractions by density-gradient centrifugation. The specific activities per cell were determined for glucose-6-phosphate dehydrogenase (EC 1.1.1.49), glutathione peroxidase (EC 1.11.1.9), glutathione reductase (EC 1.6.4.2) and catalase (EC 1.11.1.6). Decreased specific activities were observed with increasing cell age for all four enzymes in both young and old animals. In addition, significant differences in the activities of these enzymes were observed between cells of the same age fraction from young and old donors. Susceptibility of fractionated erythrocytes to oxidative attack in vitro generated by incubation with xanthine/xanthine oxidase increased with both cell and animal age. The amount of membrane-lipid peroxidation also increased with cell and animal aging, as measured by both thiobarbituric acid and fluorescent chromolipid assays. Increases of 2-3-fold in the contents of lipid peroxides were observed between the youngest and oldest age fractions of young rats. Lipid peroxide contents in young cells of old animals were equal to those in old erythrocytes from young rats and increased by 30% with cell aging in the old donors. These results suggest that the extent of enzymic protection against oxidative and peroxidative damage decreases with erythrocyte aging. More importantly, enzymic protection in cells of old rats is considerably decreased already in the early stages of their lifespan.
 ...
PMID:Decreased enzymic protection and increased sensitivity to oxidative damage in erythrocytes as a function of cell and donor aging. 671 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>