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

Impairment of lysosomal stability due to reactive oxygen species generated during the oxidation of hypoxanthine by xanthine oxidase was studied in rat liver lysosomes isolated in a discontinuous Nycodenz gradient. Production of O2.- and H2O2 during the hypoxanthine/xanthine oxidase reaction occurred for at least 5 min, while lysosomal damage, indicated by the release of N-acetyl-beta-glucosaminidase, occurred within 30 s, there being no further damage to these organelles thereafter. The extent of lysosomal enzyme release increased with increasing xanthine oxidase concentration. Superoxide dismutase and catalase did not prevent lysosomal damage during the hypoxanthine/xanthine oxidase reaction. Lysosomes reduced xanthine oxidase activity, as assessed in terms of O2 consumption, only slightly but substantially inhibited in a competitive manner the O2.- -mediated reduction of cytochrome c. This inhibition was almost completely reversed by potassium cyanide, thus pointing to the presence of a cyanide-sensitive superoxide dismutase in the lysosomal fraction. However, potassium cyanide did not affect the hypoxanthine/xanthine oxidase-mediated lysosomal damage, thus suggesting an inability of the lysosomal superoxide dismutase to protect the organelles. Negligible malondialdehyde formation was observed in the lysosomes either during the hypoxanthine/xanthine oxidase reaction or with different selective experimental approaches known to produce lipid peroxidation in other organelles such as microsomes and mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lysosomal enzyme leakage during the hypoxanthine/xanthine oxidase reaction. 256 86

Xanthine oxidase-derived oxidants and leukocytes have been implicated in the microvascular injury associated with reperfusion of ischemic intestine. The objective of this study was to determine whether xanthine oxidase-derived oxidants play a role in the leukocyte-microvascular interactions initiated by ischemia-reperfusion. Adherence and extravasation of leukocytes were monitored in cat mesenteric venules subjected to 1 h of ischemia (blood flow reduced to 20% of control) and reperfusion. Leukocyte rolling velocity, vessel diameter, and red cell velocity were also measured in control (untreated) animals and in animals pretreated with either allopurinol or superoxide dismutase. The responses of venular blood flow, wall shear rate, and leukocyte rolling velocity to ischemia and reperfusion did not differ between the three experimental groups. In control animals, 1 h of ischemia was associated with significant adherence and extravasation of leukocytes with reperfusion greatly enhancing these responses. Allopurinol treatment did not alter the responses to ischemia per se, yet it largely prevented the further increment in adherence and extravasation associated with reperfusion. Superoxide dismutase treatment attenuated the leukocyte responses elicited by both ischemia and reperfusion. Our observations that both allopurinol and superoxide dismutase attenuate reperfusion-induced leukocyte adherence and extravasation are consistent with the hypothesis that xanthine oxidase-derived oxidants initiate the leukocyte infiltration induced by reperfusion of ischemic intestine.
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PMID:Leukocyte adherence to venular endothelium during ischemia-reperfusion. 259 4

Dialyzed cell-free extract of lactobacilli was found to contain superoxide dismutase activity by using a test system in which superoxide ion is generated by xanthine oxidase. The specific activities of Lactobacillus acidophilus ATCC 4356, Lactobacillus murinus ATCC 35020, Lactobacillus acidophilus CRL 358, Lactobacillus plantarum ATCC 8014, Lactobacillus casei CRL 431, Lactobacillus plantarum CRL 353, Lactobacillus fermentum ATCC 9338, Lactobacillus buchneri NCDO 110, and Lactobacillus fermentum CRL 251 were between 0.06 and 0.43 U/mg protein. The presence of superoxide dismutase activity was demonstrated when the strains were grown in media containing Mn2+ ions. Superoxide dismutase of lactobacilli may be an Mn enzyme since it was not inhibited by either cyanide or azide ions. However, the cell-free extract of Lactobacillus murinus ATCC 35020 contains superoxide dismutase activity sensitive to both ions.
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PMID:Superoxide dismutase activity in some strains of lactobacilli: induction by manganese. 263 48

A differentiation-arrested primary cell culture model was used to examine the role of reactive oxygen species in the control of prostacyclin (PGI2) production in the perinatal rat lung. Coincubation of the lung cells with arachidonic acid (AA) and xanthine (X, 0.25 mM) plus xanthine oxidase (XO, 10 mU/ml) or with AA and glucose (25 mM) plus glucose oxidase (25 mU/ml) augmented the AA-induced PGI2 output. Superoxide dismutase (10 U/ml) did not alter the X + XO effect, whereas catalase (10 U/ml) eliminated both X + XO and glucose plus glucose oxidase effects. H2O2 (1-200 microM) showed a dose-related biphasic augmentation with peak stimulation at 20 microM. Catalase again blocked this effect, but dimethylthiourea, a hydroxyl radical scavenger, did not. A 20-min pretreatment of the cells with X + XO, glucose plus glucose oxidase, or H2O2, however, diminished the capacity of the cells to convert exogenous AA to PGI2. This pretreatment effect was also blocked by catalase. The responses were similar in lung cells obtained from day 20 rat fetuses (term = 22 days) and 1-day-old newborn rats. Lactate dehydrogenase release was not detected during treatment periods but increased significantly after exposure to reactive oxygen species.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of reactive oxygen species on prostacyclin production in perinatal rat lung cells. 265 89

Oxygen free radicals (OFR) have been implicated as a causative factor of cell damage in several pathologic conditions. It is possible that OFR could have effects on cardiac function and contractility. The present investigation deals with the effects of OFR in the absence and in the presence of scavangers of OFR (superoxide dismutase and catalase) on cardiac function, index of cardiac contractility, serum creatine kinase (CK), and blood lactate, PO2 and pH in the anesthetized dogs. The hemodynamic measurements and collection of blood samples for measurement of CK, lactate, PO2 and pH were made before and at various intervals after administration of OFR for 1 hour. Xanthine and xanthine oxidase were used to generate OFR. OFR produced a decrease in cardiac function and indices of myocardial contractility and an increase in the serum CK. OFR produced an increase in the systemic and pulmonary vascular resistance. Although there was a tendency for an increase in the blood lactate, the increase was not significant. The blood PO2 and pH were not affected. Superoxide dismutase (SOD), alone or in combination with catalase, tended to protect cardiac function against the deleterious effects of OFR. Scavangers of OFR prevented the OFR-induced rise in serum CK. Although the protective effect of SOD plus catalase was slightly better than SOD alone, the results were not significantly different from each other. These results suggest that OFR are cardiac depressant and increase the peripheral vascular resistance besides causing cellular damage. Scavangers of OFR may be beneficial in counteracting the deleterious effects of OFR on hemodynamic parameters and cellular integrity.
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PMID:Effect of oxygen free radicals on cardiovascular function at organ and cellular levels. 272 49

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but a possible role for reactive oxygen metabolites has been postulated. We evaluated whether developmental differences exist in the levels of 1) the free radical-generating enzyme xanthine oxidase, 2) granulocyte peroxidase, an index of the resident granulocyte population, 3) free radical-scavenging enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and 4) reduced glutathione, an endogenous antioxidant, in the ileal and colonic mucosa of 1-d-old, 3-d-old, 2-wk-old, and 1-mo-old piglets. We found no xanthine dehydrogenase/oxidase activity in 1-d to 1-mo-old piglets. Mucosal granulocyte peroxidase activity was higher in older animals, indicating that there was an age-dependent infiltration of granulocytes (eosinophils, neutrophils) in the distal bowel. The peroxidase activity per circulating granulocyte, however, did not vary with age. Superoxide dismutase activity was significantly higher in 1-d-old piglets than in all older age groups; glutathione peroxidase activity was significantly lower in 1-d-old animals than that of older age groups. There was no detectable catalase activity in the mucosa when tissue was corrected for catalase activity of blood. Finally, ileal GSH levels were significantly lower in 1-d-old than in 2-wk-old and 1-mo-old animals, whereas colonic reduced glutathione activity did not differ among age groups. In conclusion, the distal bowel of the neonatal piglet appears to have a limited capacity to generate oxidants via xanthine oxidase and resident granulocytes. However, the neonatal piglet intestine has a lower capacity to detoxify hydrogen peroxide than that of older animals.
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PMID:Developmental biology of oxidant-producing enzymes and antioxidants in the piglet intestine. 274 Jan 52

The calcium-channel inhibiting agent, diltiazem, has been shown to enhance salvage of reperfused myocardium independent of effects on coronary blood flow or myocardial work. Because lipid peroxidation may be a mediator of reperfusion injury and modifiable by calcium-sensitive pathways, we evaluated the effects of diltiazem on the formation of malondialdehyde (MDA), a product of lipid peroxidation, in isolated rabbit hearts perfused with buffer under control conditions or after 60 minutes of ischemia with or without 3 minutes of reperfusion. Diltiazem (5 x 10(-7)M) reduced tissue MDA content in seven reperfused hearts compared with levels measured in 14 hearts reperfused without drug (1.54 +/- 1.09 [SD] compared with 3.57 +/- 1.88 nmol/g, p less than 0.05). Superoxide dismutase and catalase were ineffective in reducing tissue MDA content in reperfused hearts (n = 8; MDA concentration, 3.88 +/- 2.82 nmol/g) although they were effective in preventing lipid peroxidation in separate studies in which oxygen-centered free radicals were generated directly by an infusion of xanthine oxidase and hypoxanthine. These results suggest that the salutary effects of diltiazem in the setting of reperfusion may be mediated by reduction of lipid peroxidation at a locus not accessible to scavengers of oxygen-centered free radicals or by a mechanism not mediated by free radical pathways.
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PMID:Reduction of lipid peroxidation in reperfused isolated rabbit hearts by diltiazem. 276 94

Freshly isolated adult rat heart cells were used to study the effects of oxygen-free radicals on the myocardial oxidation of different substrates. The calcium-tolerant quiescent cells were incubated with xanthine plus xanthine oxidase as the source of free radicals. The oxidation of exogenous glucose, lactate and octanoate was severely inhibited (approx. 70%) by products of xanthine oxidase activity. Superoxide dismutase plus catalase effectively prevented the inhibition of oxidation. Cellular high energy phosphate levels were decreased in the presence of the oxygen free radical generating system although cell viability determined by Trypan blue exclusion and light microscopic assessment of normal morphology was not affected. These data suggest that oxygen free radicals decrease myocardial substrate oxidation which may contribute to the functional and ultrastructural changes in the myocardium under conditions such as reoxygenation after hypoxia and reperfusion after ischemia.
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PMID:Effects of oxygen radicals on substrate oxidation by cardiac myocytes. 282 38

Potassium superoxide (KO2) and xanthine-xanthine oxidase (X-XO), which are known generating systems for the superoxide anion, have different inactivating actions on Bacillus subtilis transforming DNA in vitro. Superoxide dismutase and CuSO4 enhanced the inactivation for KO2, but not for X-XO. Mannitol, a hydroxyl radical scavenger, protected against the inactivation by X-XO, but not by KO2. The results obtained with X-XO were consistent with the involvement of Fenton reactions, in which hydroxyl radical is the reactive species that ultimately causes damage. On the other hand, KO2-induced inactivation was partly due to the effect of H2O2. Differences in inactivation between the KO2 and X-XO systems may result from the different rates of production of the superoxide anion.
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PMID:Comparison of the inactivation of Bacillus subtilis transforming DNA by the potassium superoxide and xanthine-xanthine oxidase systems for generating superoxide. 282 44

We studied the cytotoxic effects of ferric nitrilotriacetate (Fe-NTA) on normal rat liver epithelial cells (RL34) cultured in medium containing 10% fetal calf serum. Marked cytolysis was present in cells exposed to greater than or equal to 25 micrograms/ml iron of Fe-NTA, but not all the cells exposed to 50 micrograms/ml iron were lethally injured. The remaining cells showed anomalous growth, namely cell pile-up and aggregation. Superoxide dismutase inhibited this iron-induced cytotoxicity, whereas catalase, mannitol, dimethyl sulfoxide, and 1,4-diazabicyclo-[2.2.2.] octane did not. RL34 cells exposed to Fe-NTA actually produced a large amount of superoxide radicals (O2-.), whereas unexposed control cells produced none. Allopurinol inhibited O2-. production and prevented cell injury by Fe-NTA. These results show that the injury to cells produced by Fe-NTA depends on the generation of O2-., the source of which may be xanthine oxidase.
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PMID:Role of superoxide radicals in cytotoxic effects of Fe-NTA on cultured normal liver epithelial cells. 282 65


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