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)

Tissue changes consistent with oxidative damage in hypoxic/reoxygenated heart tissue have not been well documented. We recently reported that oxidative perturbations were evident in isolated-perfused rat heart tissue subjected to as little as 10 min hypoxia and that these changes were not exacerbated by reoxygenation. The mechanism and species specificity of this finding is not known. Rabbit hearts, which lack measurable xanthine oxidase activity, were examined for evidence of hypoxia-induced injury. The release of lactate dehydrogenase into the coronary effluent gradually increased during the retrograde perfusion of isolated rabbit hearts with hypoxic medium (containing 10 mM glucose and 2.5 mM calcium), and was slightly enhanced upon reoxygenation after 60 min hypoxia. Cardiac glutathione content decreased significantly while glutathione disulfide, protein-glutathione mixed disulfides, thiobaribturic acid reactive substances (TBARS), and protein carbonyl contents increased significantly after 60 min of hypoxia, compared to oxygenated controls. These values were unaltered after 4 min of reoxygenation except for a loss of TBARS. The oxidative changes observed in hypoxic rabbit hearts may be caused by energy deficiency impairing normal reductive processes or by the generation of reactive oxygen species as a result of abnormal cell functions, but cannot be related to xanthine oxidase activity.
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PMID:Oxidative changes in hypoxic-reoxygenated rabbit heart: a consequence of hypoxia rather than reoxygenation. 206 Aug 63

The changes in short circuit current (electrogenic Cl- secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H2O2, and the lack of effect of preincubation with deferoxamine or thiourea implicate H2O2, and not O2- or OH., as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H2O2 stimulated colonic PGE2 and PGI2 production 8- and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic Cl secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. Cl- secretion was reduced by cyclooxygenase inhibition. Also, the Cl- secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H2O2 appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE2, was blocked by tetrodotoxin. Therefore, PGI2 may be the mediator of the H2O2 response. H2O2 produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport.
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PMID:Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport. 216 49

The effect of H2O2 on the active transport of serotonin (5-HT) by human platelets was investigated. Platelets were exposed to either a single dose of H2O2 or to H2O2 generated by the glucose/glucose oxidase or xanthine/xanthine oxidase enzyme systems. H2O2 (12.5 to 100 microM) produced a rapid, concentration-dependent and time-dependent increase in 5-HT transport which was maximal after a 2-min incubation and decreased with continued incubation. Catalase (1000 units) completely prevented H2O2-induced stimulation, and fluoxetine (1 microM) totally blocked 5-HT uptake into stimulated platelets. The glucose/glucose oxidase (3.12 to 100 milliunits) and the xanthine/xanthine oxidase system, superoxide dismutase (250 units) failed to alter the stimulation, whereas catalase (1000 units) effectively prevented the response. The kinetics of 5-HT transport indicated that H2O2 treatment did not alter the Km of 5-HT transport (Km control = 1.0 +/- 0.2 x 10(-6) M vs Km H2O2 = 1.1 +/- 0.1 x 10(-6) M) but markedly increased the maximal rate of 5-HT transport (Vmax control = 131.4 +/- 4.6 pmol/10(8) platelets/4 min vs Vmax H2O2 = 206.7 +/- 9.1 pmol/10(8) platelets/4 min). These data demonstrated that exposure of human platelets to H2O2 resulted in a stimulation of the active transport of 5-HT and suggested that H2O2 may function to regulate this process.
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PMID:Stimulation of the active transport of serotonin into human platelets by hydrogen peroxide. 216 92

Respiratory activity of isolated rat liver mitochondria was assayed following in vitro exposure to oxygen radicals. Our results show that mitochondrial respiration is more sensitive to O2.(-) than to H2O2. However, ferrous ions drastically enhance the toxicity of the enzymatic system generating H2O2 because of the production of the hydroxyl radicals. A protection against those oxygen species could be given by SOD in the xanthine/xanthine oxidase system and by catalase with the glucose/glucose oxidase system. The most damaging system was the combination of Fe2+ with H2O2. In this case, OH. is formed in a Fenton-like reaction. The fact that the OH. is the most damaging molecule accounts for the finding that catalase and desferrioxamine were efficient protectors in this system. Threshold levels of O2.(-) and H2O2 able to inhibit the mitochondrial respiration have been estimated. It is concluded that under normal respiration such thresholds are not reached in vivo and that the impairment of the mitochondrial respiratory activity does not seem to originate only from the natural free radical production in those organelles. However, if the production of free radicals is such to exceed the defense capability, like under oxidative stress, then the critical threshold can be surpassed and the respiration impaired leading to irreversible damages.
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PMID:Respiratory activity of isolated rat liver mitochondria following in vitro exposure to oxygen species: a threshold study. 230 96

The effects of cell-free generated oxidants on migrating and developing stages of Schistosoma mansoni were investigated and the levels of antioxidant enzymes and of glutathione were determined for each stage. Schistosomula and 2-week-old parasites recovered from the livers of infected mice showed similar susceptibility to killing by added hydrogen peroxide and t-butylhydroperoxide. However, when glucose (0.5 mM)-glucose oxidase (2.5 mU ml-1) and xanthine (0.5 mM) or hypoxanthine (0.5 mM)-xanthine oxidase (5.0 mU ml-1) systems were used to generate hydrogen peroxide and oxygen free-radicals, schistosomula were more susceptible to oxidative killing than the 2-week-old parasites. The 4- and 8-week-old worms were more resistant to oxidants than all of the younger stages. High levels of superoxide dismutase (16.2-24.8 U mg-1 protein) were present in all stages. Catalase was not detected. Glutathione peroxidase activity with cumene hydroperoxide as substrate was not detectable in the schistosomula but the activity was present in the 2-week-old parasites. However, hydrogen peroxide-sensitive glutathione peroxidase activity was present in all the stages with a threefold difference in activity between schistosomula and the adult stages. Glutathione-s-transferase activity was significantly lower in the schistosomula, lung stages, and the 2-week-old parasites than in the older stages. Progressive increases in the levels of glutathione reductase and glutathione were also observed with development. The differences in the levels of antioxidants between different stages of development may partly explain the increase in resistance to oxidant-mediated damage as the parasite develops.
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PMID:Schistosoma mansoni: levels of antioxidants and resistance to oxidants increase during development. 232 92

The mechanism by which hypoxia leads to irreversible cellular damage is poorly understood. A decrease in purine nucleotides is common to all ischaemic tissues, yielding hypoxanthine as the substrate of the xanthine oxidase reaction. Excessive production of radicals via xanthine oxidase induces peroxidation of unsaturated fatty acids, accompanied with the formation of aldehydes. The nucleotides and aldehydes were determined by high-performance liquid chromatography (HPLC) of red blood cell extracts. Nucleotides and their derivatives were determined by HPLC on an ODS column and elution with 10 mM phosphate buffer containing 2 mM tert.-butylammonium phosphate. The aldehyde production in glucose deprived red blood cells was stimulated by addition of xanthine oxidase and by inhibition of different haemotype enzymes with sodium azide. Aldehydes were analysed by derivatization to dinitrophenylhydrazones, followed by thin-layer chromatographic and HPLC separation with aqueous methanol on an ODS column. The HPLC methods presented are appropriate for the determination of nucleotides, nucleosides and nucleobases, in addition to alkenals and hydroxyalkenals in extracts of oxidatively stressed red blood cells.
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PMID:Interrelation between nucleotide degradation and aldehyde formation in red blood cells. Influence of xanthine oxidase on metabolism: an application of nucleotide and aldehyde analyses by high-performance liquid chromatography. 238 Feb 99

Isolated Langendorff-perfused rat hearts after 10 minutes preperfusion, were subjected to a substrate-free anoxic perfusion (20 minutes) followed by 20 minutes reperfusion with a glucose-containing oxygen-balanced medium. Under the same perfusion conditions, the effect of exogenous 5mM fructose-1,6-bisphosphate has been investigated. The xanthine dehydrogenase to xanthine oxidase ratio, concentrations of high-energy phosphates and of TBA-reactive material (TBARS) were determined at the end of each perfusion period in both control and fructose-1,6-bisphosphate-treated hearts. Results indicate that anoxia induces the irreversible transformation of xanthine dehydrogenase into oxidase as a consequence of the sharp decrease of the myocardial energy metabolism. This finding is supported by the protective effect exerted by exogenous fructose-1,6-bisphosphate which is able to maintain the correct xanthine dehydrogenase/oxidase ratio by preventing the depletion of phosphorylated compounds during anoxia. Moreover, in control hearts, the release of lactate dehydrogenase during reperfusion, is paralleled by a 50% increase in the concentration of tissue TBARS. On the contrary, in fructose-1,6-bisphosphate-treated hearts this concentration does not significantly change after reoxygenation, while a slight but significant increase of lactate dehydrogenase activity in the perfusates is observed. On the whole these data indicate a direct contribution of oxygen-derived free radicals to the worsening of post-anoxic hearts. A hypothesis on the mechanism of action of fructose-1,6-bisphosphate in anoxic and reperfused rat heart and its possible application in the clinical therapy of myocardial infarction are presented.
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PMID:Oxygen radical injury and loss of high-energy compounds in anoxic and reperfused rat heart: prevention by exogenous fructose-1,6-bisphosphate. 239 20

We have studied changes in intracellular localization and phosphorylating activity of protein kinase C (PKC) in mouse epidermal JB6 cells treated with oxidants. Exposure to hydrogen peroxide, reagent grade or generated enzymatically by glucose/glucose oxidase, at concentrations known to result in elevated intracellular free Ca2+ resulted in an increase in binding of [3H]phorbol dibutyrate to intact cells. Ca2+ chelation, either intracellularly by quin 2 or extracellularly by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, abolished the increase in radioligand binding. In contrast to H2O2, superoxide generated extracellularly by xanthine/xanthine oxidase or intracellularly by menadione was inactive. Scatchard plot analysis revealed that the enhancement in binding resulted from both increased receptor affinity and increased maximal binding capacity. Treatment of cells with superoxide, generated extracellularly by xanthine/xanthine oxidase or intracellularly by menadione, diminished the [3H]phorbol dibutyrate-binding capacity of the cytosol fractions prepared at low Ca2+ concentration. This decrease was not accompanied by a compensatory increase in the binding to membrane components. In contrast to superoxide, reagent H2O2, H2O2 produced by glucose/glucose oxidase, and the Ca2+ ionophore A23187 had no significant effect on the [3H]phorbol dibutyrate-binding capacities of either cellular fraction. Exposure of cells to low concentrations of extra- or intracellular superoxide resulted in an increase in the Ca2+- and phospholipid-dependent phosphorylating activity of cytosolic extracts towards adenosine diphosphoribose transferase which has been reported to be a specific substrate for PKC. The increase in phosphorylation could be diminished by the extracellular addition of copper-zinc-containing superoxide dismutase but not catalase suggesting that superoxide rather than H2O2 represents the active oxygen species in this reaction. The observation that reagent H2O2 or glucose/glucose oxidase failed to increase the phosphorylating activity of cytosolic preparations supports this conclusion. Treatment of cells or cytosolic extracts with the sulfhydryl reagent diamide stimulated the Ca2+/phospholipid-dependent phosphorylating activity toward adenosine diphosphoribose transferase. In a reconstituted system containing purified PKC, diamide induced a 25-30% increase in phospholipid-dependent phosphorylation of H1 whereas no change in activity was observed with the reducing agent dithiothreitol. It is concluded that H2O2 but not superoxide induces an increase in the phorbol ester binding, presumably to PKC, of intact JB6 cells. On the other hand
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PMID:Translocation and enhancement of phosphotransferase activity of protein kinase C following exposure in mouse epidermal cells to oxidants. 250 33

During the reductive process in the tissues, the aerobes generate a number of oxidants. Unless these oxidants are reduced, oxidative damage and cell death would occur. Oxidation of plasma membrane lipids leads to autocatalytic chain reactions which eventually alter the permeability of the cell. The role of oxidative damage in the pathophysiology of diabetic complications and ischemic reperfusion injury of myocardium, especially the changes in the channel activity which may lead to arrhythmia have been studied. Hyperglycemia activates aldose reductase which could efficiently reduce glucose to sorbitol in the presence of NADPH. Since NADPH is also aldose required by glutathione reductase for reducing oxidants, its diversion would lead to membrane lipid oxidation and permeability changes which are probably responsible for diabetic complications such as cataractogenesis, retinopathy, neuropathy etc. Antioxidants such as butylated hydroxy toluene (BHT) and also reductase inhibitors prevent or delay some of these complications. By using patch-clamp technique in isolated frog myocytes, we have shown that hydroxy radicals generated by ferrous sulfate and ascorbate as well as lipid peroxides such as t-butyl hydroperoxide facilitate the entry of Na+ by oxidizing Na+-channels. Increased intracellular Na+ leads to an increase in Na+/Ca2+ exchange. The increased Na+ concentration by itself may produce electrical disturbance which would result in arrhythmia. Increased Ca2+ may affect proteases and may help in the conversion of xanthine dehydrogenase to xanthine oxidase, consequently increased production of super oxide radicals. Increased membrane lipid peroxidation and other oxygen free-radical associated membrane damage in myocytes has been demonstrated.
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PMID:The effect of oxidants on biomembranes and cellular metabolism. 251 41

To investigate mechanisms of ATP depletion in human umbilical vein endothelial cells after oxidant injury, we studied the relationship between DNA damage, activation of the DNA-repairing enzyme poly ADP-ribose polymerase, NAD depletion, and ATP depletion. We found that oxidant stress generated with hypoxanthine-xanthine oxidase and glucose-glucose oxidase resulted in profound DNA damage. When endothelial cells were exposed to 25 and 50 mU/ml xanthine oxidase for 60 min, the percentage of double-stranded DNA was significantly reduced (p less than 0.05) to 15.2 +/- 1.2 and 4.6 +/- 0.5%, respectively, compared to 75.7 +/- 3.9% for control cells. When endothelial cells were exposed to 25 and 50 mU/ml glucose oxidase for 60 min, the percentage of double-stranded DNA was significantly (p less than 0.05) reduced to 35.0 +/- 1.5% and 9.9 +/- 7.7%, respectively, compared to 73.2 +/- 2.4% for control cells. ATP and NAD levels declined simultaneously with DNA damage. Because activation of the DNA-repairing enzyme poly ADP-ribose polymerase can consume NAD sufficient to interfere with ATP synthesis, we studied NAD and ATP levels after oxidant injury when ADP-ribose polymerase was inhibited with 3-aminobenzamide and nicotinamide. When poly ADP-ribose polymerase was inhibited, NAD levels remained normal, but ATP depletion was not prevented. We conclude that oxidant injury to human umbilical vein endothelial cells results in profound DNA damage and NAD and ATP depletion. NAD depletion results from activation of poly ADP-ribose polymerase, but this phenomenon is not the mechanism of ATP depletion in human umbilical vein endothelial cells.
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PMID:Mechanisms of endothelial cell ATP depletion after oxidant injury. 252 33


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