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)

Molybdenum hydroxylase activity in guinea pig liver has been compared with that of marker enzymes in mitochondria (succinate dehydrogenase), microsomes (glucose-6-phosphatase) and cytosol (lactate dehydrogenase). Aldehyde oxidase activity was highest in the cytosol, with about 10-fold activity of xanthine oxidase. Significant molybdenum hydroxylase activity was found in mitochondria with minimal levels in microsomes. Mitochondrial and cytosolic aldehyde oxidase varied in substrate specificity and electrophoretic mobility with two major bands in each fraction, one of which was common to cytosol and mitochondria.
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PMID:Subcellular localisation of guinea pig hepatic molybdenum hydroxylases. 159 89

Neutrophils migrate to areas of inflammation and, when stimulated, produce O2-, H2O2, and other reactive O2 metabolites. To assess the effects of stimulated neutrophils on enterocytes, rat enterocytes were incubated with peripheral neutrophils. To assess cell viability, trypan blue exclusion and lactate dehydrogenase and protein release were measured. When 10(6) enterocytes/mL were incubated with 2.5 x 10(5) neutrophils/mL stimulated with phorbol myristate acetate, trypan blue exclusion decreased and lactate dehydrogenase and protein release increased. With the addition of 0.10 mg/mL of superoxide dismutase, trypan blue exclusion further decreased and lactate dehydrogenase and protein release increased. This suggests that H2O2- or H2O2/O2(-)-derived metabolites are more damaging to isolated enterocytes than O2-. To test this hypothesis, enterocytes were incubated with xanthine and increasing concentrations of xanthine oxidase in the presence and absence of superoxide dismutase. With increasing concentrations of xanthine oxidase, the cell number decreased and protein release increased. With the addition of superoxide dismutase, fewer cells were present, suggesting that cell lysis occurred. Protein release was further increased by the addition of superoxide dismutase. Enterocytes were then incubated with leucine and increasing concentrations of amino acid oxidase. With increasing concentrations of amino acid oxidase, trypan blue exclusion decreased and protein and lactate dehydrogenase release increased. These effects were ameliorated by the addition of 500 IU catalase/mL. These data suggest that O2- and H2O2, whether created by stimulated neutrophils or an enzyme-generating system, are damaging to isolated enterocytes. Superoxide dismutase did not offer enterocytes protection.
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PMID:Rat enterocyte injury by oxygen-dependent processes. 165 Mar 18

1. Nilvadipine (FK 235, FR 34235) suppressed ischemia (20 min)-reflow (20 min)-induced paw edema of mice (ED30:0.4 mg/kg i.v. and 2 mg/kg p.o.). Other calcium entry blockers of dihydropyridine-type also suppressed the edema, but 30-fold higher doses were required. 2. Oral dosing of nilvadipine suppressed carrageenan-induced paw edema (ED30:15 mg/kg in rats and 20 mg/kg in mice) at a potency corresponding to that of an anti-inflammatory drug, ibuprofen. Nifedipine, nicardipine and nimodipine resulted in a suppression of 30% only with 100 mg/kg oral dosing in rats. Nitrendipine, diltiazem and verapamil were without effect. 3. Nilvadipine inhibited superoxide radical (O-2production from xanthine oxidase (XOD) both with lactate dehydrogenase + NADH method and cytochrome c method (IC50:90 and 100 micrograms/ml, respectively). Nifedipine and nicardipine showed some inhibition, but the other calcium entry blockers failed to inhibit significantly even at 320 micrograms/ml. As uric acid formation was not reduced by the tested drugs, the inhibitory action might be due to their O-2scavenging effects. 4. Superoxide production of neutrophils from casein-induced peritoneal fluid in rats was most strongly inhibited by nilvadipine when the cells were stimulated by a calcium ionophore, A23187 (IC50:4 micrograms/ml). Inhibition by this drug when stimulated by f-methonyl-leucyl-phenylalanine and phorbol myristate acetate was less effective (IC50:20 and 30 micrograms/ml, respectively). Nifedipine and nicardipine inhibited neutrophil O-2production at higher concentrations (30-200 micrograms/ml) with all stimulants. Inhibitory actions by other drugs were weak. 5. Triggering of atherosclerosis depends largely on the oxidative stress on blood vessels after recently established concept.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition by nilvadipine of ischemic and carrageenan paw edema as well as of superoxide radical production from neutrophils and xanthine oxidase. 165 7

The geographic distribution of the following enzyme systems is described in the rat heart (left and right ventricles) and in different skeletal muscles (soleus, plantaris, and red and white gastrocnemius): xanthine oxidase and dehydrogenase, creatine kinase isoenzymes, lactate dehydrogenase isoenzymes, and the free radical scavenger enzymes superoxide dismutase, glutathione reductase, and glutathione peroxidase. No substantial difference in enzyme activities was observed between the left and right ventricles. Skeletal muscles showed a clear distinction between enzyme activities depending on their composition of oxidative fibers and glycolytic fibers.
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PMID:Geographic distribution of xanthine oxidase, free radical scavengers, creatine kinase, and lactate dehydrogenase enzyme systems in rat heart and skeletal muscle. 175 94

Understanding of the mechanisms of cell injury and cell death is fundamental to the understanding of both protection against and initiation of cell injury and cell death. We subjected primary cultures of proximal tubular epithelium (PTE) from adult rats to an exogenous oxidative stress, generated by xanthine/xanthine oxidase (X/XOD), and studied its effect on the concentration of cytosolic ionized calcium ([Ca2+]i) by means of digital imaging fluorescence microscopy (DIFM) using a cytosolic calcium probe, fura-2. Exposure to 25 mU/ml X/XOD caused notable increases in [Ca2+]i detectable within 15 sec and increasing to micromolar levels with time. Experiments with Ca(2+)-free medium containing ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) showed that the increase of [Ca2+]i was due to influx from the extracellular space. Smaller and slower increases in [Ca2+]i were seen after exposure to lower concentrations of X/XOD (5 and 10 mU/ml). PTE injury and killing were assessed by measuring the release of cytosolic lactate dehydrogenase (LDH), exclusion of trypan blue, and observation of morphologic changes. Exposures to the 25 mU/ml concentration of X/XOD caused significant LDH release after 2 hr and correlated with trypan blue staining of exposed cells. Again, lesser concentrations of X/XOD resulted in a slower release of smaller amounts of LDH, and thus delayed trypan blue staining. Cytoplasmic bleb formation was seen by phase microscopy within minutes of exposure to 25 mU/ml, followed by cell rounding, retraction, and disintegration. Transmission electron microscopy revealed a progression of changes characteristic of lethal cell injury, beginning with dilatation of the endoplasmic reticulum, detachment of ribosomes, condensation of mitochondria, and chromatin clumping and terminating with mitochondrial swelling and formation of intramitochondrial flocculent densities. These studies clearly show that notable increases of [Ca2+]i precede both sub-lethal and lethal changes in rat PTE. These results indicate that interventions designed to minimize or to accelerate calcium entry could be of importance in cell preservation or cell killing, respectively, and therefore to therapeutic strategies for myocardial infarction, stroke, or shock in the former instance and for cancers in the latter.
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PMID:Oxidative injury induces influx-dependent changes in intracellular calcium homeostasis. 177 66

The rates of NADH oxidation in presence of xanthine oxidase increase to a small and variable extent on addition of high concentrations of lactate dehydrogenase and other dehydrogenases. This heat stable activity is similar to polyvanadate-stimulation with respect to pH profile and SOD sensitivity. Isocitric dehydrogenase (NADP-specific) showed heat labile, SOD-sensitive polyvanadate-stimulated NADH oxidation activity. Polyvanadate-stimulated SOD-sensitive NADH oxidation was also found to occur with riboflavin, FMN and FAD in presence of a non-specific protein, BSA, suggesting that some flavoproteins may possess this activity.
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PMID:Stimulation of NADH oxidation by xanthine oxidase and polyvanadate in presence of some dehydrogenases and flavin compounds. 178 72

Experiments were performed to investigate the hypothesis that exposure of vascular endothelial cells to low levels of reduced oxygen products results in DNA strand breakage as an early event and to determine if endothelial cells derived from bovine pulmonary artery demonstrate a susceptibility to oxidant injury that is different from that of cells derived from bovine aorta. Endothelial cells grown in culture were exposed to H2O2 (either added directly or generated from glucose oxidase) or superoxide radical (generated from xanthine oxidase), and DNA strand breakage was determined using fluorescent analysis of DNA unwinding. Cell injury was also assessed by measuring the release of lactate dehydrogenase (LDH) or the release of 51Cr from prelabeled cells. Whereas LDH or 51Cr release detected injury resulting from exposure of endothelial cells to greater than or equal to 100 microM H2O2 and was apparent only 2 or more h after exposure, DNA strand breakage was detectable after 15 min of exposure of endothelial cells to 50 microM H2O2. Approximately equivalent DNA strand breakage resulted from exposure to 50 microM H2O2, to 25 mU glucose oxidase, or to 10 mU xanthine oxidase; this injury is similar to that seen following exposure to 10 gray X-radiation. DNA strand breakage following exposure of cells to xanthine oxidase was preventable by catalase but not by superoxide dismutase or hydroxyl radical scavengers, suggesting that H2O2 is the active extracellular oxidant mediating DNA strand breaks. No differences were seen in the susceptibility of pulmonary artery or aortic endothelial cells to oxidant injury.
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PMID:DNA strand break formation following exposure of bovine pulmonary artery and aortic endothelial cells to reactive oxygen products. 189 51

The role of xanthine oxidase and oxygen free radicals in postischemic reperfusion injury in the rat kidney remains controversial. Proximal tubules, the focal segment affected by ischemic renal injury, were isolated in bulk, assayed for xanthine oxidase activity, and subjected to 60 min of anoxia or hypoxia and 60 min of reoxygenation to evaluate the participation of xanthine oxidase and oxygen radicals in proximal tubule reoxygenation injury. The total xanthine oxidase in isolated rat proximal tubules was 1.1 mU/mg of protein, approximately 30% to 40% of the activity found in rat intestine and liver. Lactate dehydrogenase release, an indicator of irreversible cell damage, increased substantially during anoxia (39.8 +/- 2.3 versus 9.8 +/- 1.8% in controls) with an additional 8 to 12% release during reoxygenation. Addition of 0.2 mM allopurinol, a potent xanthine oxidase inhibitor, and dimethylthiourea, a hydroxyl radical scavenger, failed to protect against the reoxygenation lactate dehydrogenase release. Analysis of xanthine oxidase substrate levels after anoxia and flux rates during reoxygenation indicates that hypoxanthine and xanthine concentrations are in a 15-fold excess over the enzyme Km and 0.3 mU/mg of protein of xanthine oxidase activity exists during reoxygenation. Hypoxic tubule suspensions had a minimal lactate dehydrogenase release during hypoxia and failed to demonstrate accelerated injury upon reoxygenation. In conclusion, although xanthine oxidase is present and active during reoxygenation in isolated rat proximal tubules, oxygen radicals did not mediate reoxygenation injury.
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PMID:Minimal role of xanthine oxidase and oxygen free radicals in rat renal tubular reoxygenation injury. 188 66

The cytotoxic effects of oxygen radicals have been studied in enriched population of mature bovine oligodendrocytes in culture. Oxygen radicals were generated enzymatically by glucose and glucose oxidase, and hypoxanthine and xanthine oxidase combinations. Cytotoxicity was assessed by trypan blue exclusion and percentage lactate dehydrogenase release into the culture media. Incubation of bovine oligodendrocytes with these oxygen radical-generating systems for 4 hr resulted in significant cell death, especially in the glucose oxidase system. The oligodendrocytes were completely protected by catalase from the cytotoxic effects of both oxygen radical generating systems. However, superoxide dismutase, dimethylsulfoxide and antioxidants such as vitamin E and glutathione did not protect oligodendrocytes from the oxidant-mediated cytotoxicity. It appears that hydrogen peroxide produced in these oxygen radical-generating systems gives rise to toxic radicals that induce the cell death of bovine oligodendrocytes in culture.
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PMID:Oligodendroglial cell death induced by oxygen radicals and its protection by catalase. 188 63

The aims of this study were to investigate the interaction between oxygen radicals and mucus secretion from cultured rat gastric mucous cells, and to assess the role of prostaglandin production in the modulation of mucus secretion in vitro. Xanthine oxidase in the presence of hypoxanthine caused a dose-dependent increase in the presence of hypoxanthine caused a dose-dependent increase of mucus secretion, as assessed by release of [3H]glucosamine from prelabeled cells, whereas xanthine oxidase or hypoxanthine alone did not. Xanthine oxidase (10 mU/ml) increased release of [3H]glucosamine by 57 +/- 6% compared with control values (P less than 0.001). Catalase (3,000 U/ml) inhibited xanthine oxidase-induced mucus secretion by 69 +/- 9% (P less than 0.01), whereas superoxide dismutase did not. Pretreatment with deferoxamine, an inhibitor of hydroxyl radical generation through chelating ferric ion, diminished oxygen radical-induced mucus release to control values. Xanthine oxidase dose dependently stimulated prostaglandin E2 (PGE2) production, which was blocked by catalase but not by superoxide dismutase. However, oxygen radical stimulation of mucus secretion was not inhibited by the addition of indomethacin. Moreover, PGE2, exogenously administered, did not significantly accelerate mucus secretion. Stimulation of mucus secretion by oxygen radicals was not accompanied by increased 51Cr release or by leakage of intracellular lactate dehydrogenase. These results suggest that oxygen species, particularly hydroxyl radical, stimulate mucous glycoprotein secretion from cultured rat gastric mucous cells. However, it seems unlikely that prostaglandin production mediates the oxygen species-induced stimulation of mucus secretion.
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PMID:Oxygen metabolites stimulate mucous glycoprotein secretion from cultured rat gastric mucous cells. 192 52


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