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)

We earlier showed that the neuropeptide vasoactive intestinal peptide (VIP) reduces or prevents acute injury produced in rat lungs by xanthine and xanthine oxidase. We have now examined whether VIP can protect against lung injury induced by paraquat, a prooxidant pesticide. Isolated guinea pig lungs were perfused for 60 min with Krebs-4% albumin and mechanically ventilated with 95% O2-5% CO2. Infusion of paraquat (100 mg/kg) into the pulmonary artery (n = 9 observations) increased peak airway pressure from 10.1 +/- 0.6 to 54.7 +/- 6.5 cmH2O, perfusion pressure from 8.0 +/- 0.5 to 14.9 +/- 3.0 cmH2O, wet-to-dry lung weight ratio to 7.17 +/- 0.37, and bronchoalveolar lavage protein content to 2.70 +/- 0.83 mg/ml (P < 0.01). Pretreatment with 1-3 micrograms.kg-1 x min-1 VIP markedly attenuated or prevented all abnormalities. Of the related peptides tested, helodermin was as effective as VIP, but secretin and glucagon were ineffective. The results demonstrate that VIP and helodermin protect perfused guinea pig lungs against paraquat-induced injury and support the view that VIP has antioxidant activity.
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PMID:Paraquat-induced lung injury: prevention by vasoactive intestinal peptide and related peptide helodermin. 823 70

Exposure to hyperbaric oxygen [3 atmospheres absolute (ATA) for 45 min] inhibited carbon monoxide (CO)-mediated lipid peroxidation in the brains of rats by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion process known to be due to the action of leukocytes. The effect was the same whether treatment was given 24 hr before or up to 45 min after poisoning. Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, based on measurements of myeloperoxidase (MPO) in microvessel segments, but persistent adherence, which is due to B2 integrins, did not occur. Exposing rats to 3 ATA pressure (0.21 ATA O2) after CO poisoning had no significant effects. A progressive reduction in brain microvessel MPO titers occurred with exposure to O2 at 1, 2, or 3 ATA after CO poisoning, but 1 ATA O2 treatment did not significantly inhibit xanthine oxidase formation or lipid peroxidation. In vitro studies with polymorphonuclear leukocytes (PMN) from rats exposed to hyperbaric oxygen corroborated the absence of PMN B2 integrin function, but when these cells were stimulated they exhibited normal B2 integrin expression on their surface and also normal elastase release and superoxide radical production. Adherence functions of PMN that do not require B2 integrins appeared to remain intact after exposure to hyperbaric oxygen, as peritoneal neutrophilia in response to a glycogen challenge was not inhibited. B2 integrin function could be restored by incubating cells with 8 bromo cGMP, and incubation with phorbol ester stimulated the adherence function of both control and hyperbaric oxygen-exposed PMN. These results provide a clear mechanism for the inhibition of CO-mediated brain lipid peroxidation by hyperbaric oxygen and indicate that hyperoxia causes a discrete disturbance of PMN adherence function.
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PMID:Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. 824 32

Reperfusion after global cardiac ischemia may injure coronary artery endothelium and lead to vasospasm and thrombosis. Oxygen-derived radicals have been implicated as mediators of this process, but the precise mechanism of injury is unknown. We hypothesized that oxygen-derived radicals impair coronary endothelial production of nitric oxide, a potent endogenous vasodilator and inhibitor of platelet adhesion. To test this theory, we developed an in vitro model of reperfusion injury in which segments of epicardial canine coronary artery were suspended in organ chambers (physiologic salt solution, 37 degrees C, 95% oxygen and 5% carbon dioxide) and exposed to oxygen-derived radicals (generated by adding xanthine [10(-4) mol/L] and xanthine oxidase [100 mU/ml] to the bathing solution for 70 minutes). After exposure to oxygen-derived radicals, epicardial coronary artery smooth muscle exhibited normal contraction to potassium ions (20 mmol/L) and prostaglandin F2 (4 x 10(-6) mol/L); also, the rings relaxed normally on exposure to isoproterenol and sodium nitroprusside (10(-9) to 10(-4) mol/L) (n = 6). In contrast, endothelium-dependent vasodilatation to receptor-dependent agonists acetylcholine and adenosine diphosphate (10(-9) to 10(-4) mol/L) was impaired as compared with the reaction of control vessels not exposed to oxygen-derived radicals (n = 18, P < 0.001, and n = 10, P < 0.002, respectively). Importantly, receptor-independent, endothelium-dependent relaxation to the calcium ionophore A23187 was normal (n = 6). Further, endothelium-dependent vasodilatation to receptor-dependent agonist bradykinin (non-nitric oxide pathway) was normal after exposure to oxygen-derived radicals. This is the first study to demonstrate that oxygen-derived radicals selectively impair receptor-dependent nitric oxide production by the coronary endothelium. Diminished nitric oxide production is a likely mechanism of vasospasm and thrombosis after reperfusion of the ischemic heart.
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PMID:Oxygen radical-mediated vascular injury selectively inhibits receptor-dependent release of nitric oxide from canine coronary arteries. 830 70

The extracellular production of singlet oxygen (O2(1 delta g)) by stimulated macrophages was measured using a modification of our quantitative method initially developed to measure the intracellular production of O2(1 delta g) by neutrophils (Steinbeck, M. J., Khan, A. U., and Karnovsky, M. J. (1992) J. Biol. Chem. 267, 13425-13433). Glass coverslips were coated with the specific chemical trap for O2(1 delta g), 9,10-diphenylanthracene (DPA) and perylene, which is an internal standard, in a methylene chloride solution containing 0.3 mg/ml polystyrene. On evaporation, the polystyrene formed an even coating of DPA and perylene over the surface of a glass coverslip (PDP film). Unstimulated macrophages or macrophages stimulated with 4 beta-phorbol 12-myristate 13-acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP) were then added to the PDP film in a darkened room and incubated at 37 degrees C for 30 min in a humidified 5% CO2 atmosphere. Both unstimulated and stimulated cells adhered to the PDP film in approximately equivalent numbers. Only stimulated cells produced measurable amounts of O2(1 delta g) in a dose-dependent response to either PMA or fMLP. The production of O2(1 delta g) by macrophages stimulated with PMA was maximal in response to 25 ng, 17.8 +/- 1.3 nmol of O2(1 delta g)/approximately 1.00 x 10(6) cells. The maximal response for fMLP was at a concentration of 1 microM, 18.4 +/- 1.0 nmol of O2(1 delta g)/approximately 1.00 x 10(6) cells. The specific detection of O2(1 delta g) by this method was confirmed by thermally releasing O2(1 delta g) from the DPA-O2(1 delta g) reaction product, DPA-endoperoxide, regenerating the original DPA compound. Production of O2(1 delta g) by the stimulated cells was inhibited 80-89% by the addition of 60-120 micrograms of superoxide dismutase, an enzyme that converts superoxide to hydrogen peroxide and ground state molecular oxygen or 79-84% with the addition of 2 mM histidine, an avid quencher of O2(1 delta g). Neither of these additions interfered with adhesion of the cells to the PDP film. The ability of superoxide dismutase to inhibit the production of O2(1 delta g) suggested that O2(1 delta g) was produced via a superoxide-dependent route. The ability of an oxidase to produce O2(1 delta g) secondary to superoxide production was substantiated further using a xanthine oxidase-acetaldehyde system. Purified xanthine oxidase produced both superoxide and O2(1 delta g), and their production was inhibited by the addition of superoxide dismutase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Extracellular production of singlet oxygen by stimulated macrophages quantified using 9,10-diphenylanthracene and perylene in a polystyrene film. 834 Mar 89

Experiments were designed to determine the effect of oxygen-derived free radicals in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution bubbled with 95% O2-5% CO2 (temperature = 37 degrees C; pH = 7.4). A radioimmunoassay technique was used to measure production of prostaglandins and thromboxane B2. Xanthine oxidase (1-9 mU/ml, in the presence of 10(-4) M xanthine) and hydrogen peroxide (10(-6) to 10(-4) M) caused concentration-dependent contractions. The removal of endothelium reversed these contractions into relaxations. Contractions to xanthine oxidase and hydrogen peroxide were inhibited in the presence of superoxide dismutase (150 U/ml), catalase (1,200 U/ml), indomethacin (10(-5) M), and SQ 29548 (10(-6) M) but not in the presence of deferoxamine (10(-4) to 10(-3) M) and dimethyl sulfoxide (10(-4) M). NG-monomethyl-L-arginine (3 x 10(-5) M) augmented the contractions to hydrogen peroxide. Xanthine oxidase stimulated production of 6-ketoprostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, and thromboxane B2. The stimulatory effect was prevented by the removal of endothelial cells. These studies suggest that xanthine oxidase causes endothelium-dependent contractions mediated by: 1) hydrogen peroxide-induced stimulation of the endothelial metabolism of arachidonic acid via the cyclooxygenase pathway, leading to activation of prostaglandin H2-thromboxane A2 receptors, and 2) inactivation of basal production of nitric oxide by superoxide anions.
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PMID:Endothelium-dependent contractions to oxygen-derived free radicals in the canine basilar artery. 845 88

Nitric oxide is a short-lived free radical and physiological mediator which has the potential to cause cytotoxicity. Studies were conducted to investigate whether nitric oxide, and the potent oxidant peroxynitrite, were generated in brain during experimental carbon monoxide (CO) poisoning in the rat. Nitric oxide production was documented by electron paramagnetic resonance spectroscopy, and found to be increased by ninefold immediately after CO poisoning. Evidence that peroxynitrite was generated was sought by looking for nitrotyrosine in the brains of CO-poisoned rats. Nitrotyrosine was found deposited in vascular walls, and also diffusely throughout the parenchyma in inummocytochemical studies. The affinity and specificity of an anti-nitrotyrosine antibody was investigated and a solid phase immunoradiochemical assay was developed to quantity nitrotyrosine in brain homogenates. A 10-fold increase in nitrotyrosine was found in the brains of CO-poisoned rats. Platelets were involved with production of nitrotyrosine in the early phase of exposure to CO. However, nitrotyrosine formation and leukocyte sequestration were not decreased in thrombocytopenic rats poisoned with CO according to the standard model. When rats were pre-treated with the nitric oxide synthase inhibitor, L-nitroarginine methyl ester, formation of both nitric oxide and nitrotyrosine in response to CO poisoning were abolished, as well as leukocyte sequestration in the microvasculature, endothelial xanthine dehydrogenase conversion to xanthine oxidase, and brain lipid peroxidation. We conclude that perivascular reactions mediated by peroxynitrite are important in the cascade of events which lead to brain oxidative stress in CO poisoning.
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PMID:Nitric oxide production and perivascular nitration in brain after carbon monoxide poisoning in the rat. 863 94

Little is known about the mechanisms of altered cell membrane function after hyperoxic exposure. We determined the effects of hyperoxic exposure and exogenous oxidant stress with xanthine/xanthine oxidase (X/XO) on Na+/H+ antiport activity. Pulmonary artery endothelial cell monolayers were incubated in 95% O2/5% CO2 (24 to 72 hours) simultaneously with controls placed in 21 % O2/5% CO2. Monolayers were then incubated for 2 hours in MEM with or without X/XO (100 micromol/L X; 0.01 U/ml XO). Antiport activity was determined as the rate of recovery from intracellular acidosis by measurement of intracellular pH (pH,) with 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). Hyperoxic exposure (72 hours) decreased Na+/H+ antiport activity as compared with that in control monolayers. Exogenous oxidant stress also decreased antiport activity in both control and hyperoxic cells, but this effect was more pronounced in hyperoxic cells at all time points. These changes occurred in the absence of overt cytotoxicity. Incubation with antioxidants (polyethylene glycol-superoxide dismutase (PEG-SOD), PEG-catalase, vitamin E), N-acetylcysteine, or phospholipase A2 (PLA2) inhibitors did not prevent the decrease in antiport activity after hyperoxic exposure. Conditioned medium experiments demonstrated that the diminished antiport activity was not related to release of a soluble mediator after hyperoxic exposure. These findings suggest that the diminished Na+/H+ antiport activity represents a sublethal form of membrane dysfunction that may be a component of the increased endothelial cell susceptibility to injury after hyperoxic exposure.
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PMID:Effect of hyperoxia and exogenous oxidant stress on pulmonary artery endothelial cell Na+/H+ antiport activity. 876 11

Acute carbon monoxide exposure produces a significant impairment in high-frequency auditory sensitivity that can be prevented using the N-methyl-D-aspartate receptor blocker MK-801. This finding suggests an excitotoxic component to carbon monoxide ototoxicity and establishes the potential for free radical formation. Free radical scavengers and inhibitors are protective in many organs, including the brain and cochlea, during hypoxic events such as ischemia/reperfusion and, in the cochlea, during noise exposure. This study evaluated the protection afforded by two such agents, phenyl-n-tert-butyl-nitrone (PBN), which acts as a general free radical scavenger, and allopurinol, which acts as a free radical inhibitor specific to the xanthine oxidase metabolic pathway. Guinea pigs were pretreated with PBN (100 mg/kg i.p.), allopurinol (100 mg/kg i.p.), or saline 1 hr prior to exposure to carbon monoxide (35 ml/kg i.p.) or to an equal volume of air. They were monitored at 15, 30, and 60 min after carbon monoxide exposure for alterations in compound action potential threshold and cochlear microphonic amplitude. The groups receiving carbon monoxide alone displayed characteristic compound action potential threshold elevations particularly at the higher test frequencies (16-40 kHz), consistent with earlier studies; no loss of cochlear microphonic amplitude was exhibited. Both free radical inhibitors, PBN and allopurinol, blocked loss of auditory threshold sensitivity produced by carbon monoxide. These data suggest that free radical generation may play a significant role in the impairment of high-frequency auditory sensitivity resulting from carbon monoxide.
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PMID:Cochlear protection from carbon monoxide exposure by free radical blockers in the guinea pig. 900 33

We investigated in vitro whether endothelial cell edema is induced by cellular hypoxia or oxygen radical formation. Measurements of relative cell volume (RCV) were made using microweight analysis, liquid scintillation spectrometry and analysis of cellular protein content. To validate this method of determining cell volume, endothelial cells were incubated in media of different osmolarities. Vascular endothelial cells reacted to osmotic stress with a volume increase or decrease. The addition of xanthine oxidase (XOD; 3 mU/ml) and hypoxanthine (1 mM) for the enzymatic production of O2- caused a reproducible and significant increase in RCV by 29 +/- 8% (from 5.5 to 7.1 microliters/10(6) cells; p < 0.001) after an incubation time of 60 min. Nonenzymatically produced H2O2 (100 microM) caused a similar increase in RCV by 35 +/- 5% (from 5.5 to 7.6 microliters/10(6) cells; p < 0.001) over the same incubation period. The addition of catalase (50 U/ml) diminished the increasing effect of XOD as well as that of H2O2 on cell volume. As assessed by the uptake of the vital dye trypan blue and the release of lactate dehydrogenase into the medium, there was no significant loss of viability during the incubation time. Lower concentrations of H2O2 as well as lower activities of XOD did not induce a significant increase in RCV. Higher H2O2 concentrations and increased XOD activities caused a considerable time- and concentration-dependent injury of endothelial cells. RCV was unchanged even after long exposure (5 h) to two different hypoxic gas mixtures (3% O2:5% CO2:92% N2; 0% O2:5% CO2:95% N2). Cell viability was not impaired under hypoxic conditions. The results suggest that reactive oxygen species play a more important role in the development of endothelial cell edema than cellular hypoxia.
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PMID:The influence of cellular hypoxia and reactive oxygen species on the development of endothelial cell edema. 925 83

Under oxidative stress, increased energy requirements are needed To induce repair mechanisms. As glucose is a major energy source in L6 myotubes, we evaluated glucose metabolism and transport, following exposure to glucose oxidase (H2O2 generating system), or xanthine oxidase (O2. and H2O2 generating system), added to the medium. Exposure for 24 h to 5 mM glucose and 50 mU/ml glucose oxidase, or to 50 microM xanthine and 20 mU/ml xanthine oxidase resulted in significant oxidant stress indicated by increased DNA binding activity of NF-kappa B. Under these conditions, approximately 2-fold increase in glucose consumption, lactate production and CO2 release were observed. 2-deoxyglucose uptake into myotubes increased time and dose dependently, reaching a 2.6 +/- 0.4-fold and 2.2 +/- 0.7-fold after 24 h exposure to glucose oxidase and xanthine oxidase, respectively. Peroxidase prevented this effect, indicating the role of H2O2 in mediating glucose uptake activation. The elevation in glucose uptake under oxidative stress was associated with increased expression of GLUT1 mRNA and protein. The observed 2-deoxyglucose uptake activation by oxidants was not limited to the L6 cell line and was observed in 3T3-L1 adipocytes as well.
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PMID:Reactive oxygen species activate glucose transport in L6 myotubes. 937 65


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