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)

Preincubation of rat brain synaptosomes with xanthine and xanthine oxidase (X/XO) in Ca2+-free Krebs buffer resulted in a 27% inhibition of synaptosomal gamma-aminobutyric acid (GABA) uptake. Addition of 1.5 mM CaCl2 increased the inhibition with X/XO to 46%, and inhibition was essentially complete when the calcium ionophore A23187 also was included. In other studies, preincubation of purified rat brain mitochondria with the combination of X/XO and 4 microM CaCl2 produced a significant (38%) decrease in state 3 respiration with glutamate/malate as substrate that was not seen with either X/XO or Ca2+ alone. Similar results were obtained using cultured mouse spinal cord neurons in which incubation with X/XO/ADP/FeCl2 and A23187 produced membrane damage as assessed by a 32% reduction of neuronal Na+, K+-ATPase activity. Neither X/XO/ADP/FeCl2 nor A23187 alone caused detectable inhibition. These results demonstrate the synergistic damaging effect of free radicals and Ca2+ on membrane function. In addition, they suggest that free radical-induced peroxidation of membrane lipid, occurring focally during complete or nearly complete ischemia in vivo, could result in intense cellular perturbation when coupled with increased intracellular Ca2+.
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PMID:Calcium enhances in vitro free radical-induced damage to brain synaptosomes, mitochondria, and cultured spinal cord neurons. 299 23

The superoxide radicals generated by the xanthine oxidase reaction reduced the myofibrillar Ca2+-ATPase activity. This negative effect was prevented by superoxide dismutase or by dithiothreitol, a protective thiol compound. Partial protection was achieved by catalase, while mannitol was ineffective. The myofibrillar Ca2+-ATPase exposed to O2-. radicals did not modify the affinity for Ca2+ while it showed a remarkable reduction of Vmax measured at the saturating level of Ca2+. The O2-. inhibited myofibrillar ATPase showed a higher value of Km for the cofactor associated to a reduced value of Vmax when studied in the presence of increasing concentration of ATP. Thus, circumstances that enhance the production of cardiac O2- radicals can be considered a negative metabolic event capable of depressing the myofibrillar Ca2+-ATPase activity.
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PMID:Inhibitory effect of superoxide radicals on cardiac myofibrillar ATPase activity. 299 80

Incubation of Trypanosoma cruzi mitochondrial ATPase (Fo-F1) with the xanthine oxidase system (XO), Fenton's reagent (Fe2+ + H2O2) and the ascorbate-Cu system, caused gradual loss of enzyme activity, which increased as a function of incubation time and rate of oxygen radical generation. The essential role of OH. radicals for ATPase inactivation was supported by a) the enzyme protection afforded by superoxide dismutase, catalase and mannitol, when using the XO system; b) the similar effect of mannitol and benzoate with Fenton's reagent; c) the similar effect of catalase, EDTA and histidine with the ascorbate-Cu system; d) the increased rate of ATPase inactivation by 1) the XO system supplemented with chelated iron, and 2) the ascorbate-Cu system supplemented with H2O2. Comparison of oxygen radical generators for their action on membrane-bound (Fo-F1) and soluble F1 revealed that ascorbate-Cu was the most effective one, possibly because of its capability of producing OH. radicals that react preferentially with the enzyme at their formation site.
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PMID:Inactivation of mitochondrial adenosine triphosphatase from Trypanosoma cruzi by oxygen radicals. 301 49

Mouse cortical synaptosomal structure and function are altered when exposed to hypoxanthine/xanthine oxidase (HPX/XOD)-generated active oxygen/free radical species. The structure of both the synaptic vesicle and plasma membrane systems are altered by HPX/XOD treatment. The alteration of synaptic vesicle structure is exhibited by a significant increase in the cumulative length of nonsynaptic vesicle membrane per nerve terminal. With respect to the nerve terminal plasma membrane, the length of the perimeter of the synaptosome is increased as the membrane pulls away from portions of the terminal in blebs. The functional lesion generated by HPX/XOD treatment results in a reduction in selective high-affinity gamma-[14C]aminobutyric acid (GABA) uptake. Kinetic analysis of the reduction in high-affinity uptake reveals that the Vmax is significantly altered whereas the Km is not. Preincubation with specific active oxygen/free radical scavengers indicates that the super-oxide radical is directly involved. This radical, most probably in the protonated perhydroxyl form, initiates lipid peroxidative damage of the synaptosomal membrane systems. Low-affinity [14C]GABA transport is unaltered by the HPX/XOD treatment. The apparent ineffectiveness of free radical exposure on low-affinity [14C]GABA transport coupled with its effectiveness in reducing high-affinity transport supports the idea that two separate and different amino acid uptake systems exist in CNS tissue, with the high-affinity being more sensitive (lipid-dependent) and/or more energy-dependent (Na+,K+-ATPase) than the low-affinity system.
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PMID:Superoxide radical-mediated alteration of synaptosome membrane structure and high-affinity gamma-[14C]aminobutyric acid uptake. 302 6

The role of O2 free radicals in the reduction of sarcolemmal Na+-K+-ATPase, which occurs during reperfusion of ischemic heart, was examined in isolated guinea pig heart using exogenous scavengers of O2 radicals and an inhibitor of xanthine oxidase. Ischemia and reperfusion reduced Na+-K+-ATPase activity and specific [3H]ouabain binding to the enzyme in ventricular muscle homogenates and also markedly lowered sodium pump activity estimated from ouabain-sensitive 86Rb+ uptake by ventricular muscle slices. These effects of ischemia and reperfusion were prevented to various degrees by O2-radical scavengers, such as superoxide dismutase, catalase, dimethyl-sulfoxide, histidine, or vitamin E or by the xanthine oxidase inhibitor, allopurinol. The degree of protection afforded by these agents paralleled that of reduction in enhanced lipid peroxidation of myocardial tissue as estimated from malondialdehyde production. These results strongly suggest that O2 radicals play a crucial role in the injury to sarcolemmal Na+-K+-ATPase during reperfusion of ischemic heart.
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PMID:O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase. 302 76

The effects of allopurinol pretreatment (1 mg/ml in the drinking water for 7 days at an estimated daily dose of 75 mg/kg) on biochemical and chemical changes occurring following left circumflex coronary artery ligation (40 min) and reperfusion (60 min) were examined in pentobarbital-anesthetized rabbits. During the ischemic phase, allopurinol pretreatment provided significant preservation of cellular ATP levels and of mitochondrial ATP generation as compared with untreated animals (P less than 0.05). During the reperfusion phase, allopurinol pretreatment significantly prevented the decrease in left ventricular pressure, sodium and calcium accumulation and decreases in sarcolemmal Na+,K+-stimulated and sarcoplasmic reticulum K+,Ca2+-stimulated ATPase activities as compared with untreated animals (P less than 0.05). In contrast, the decrease in mitochondrial (azide-sensitive) ATPase during ischemia and the partial recovery during reperfusion were unaffected by allopurinol pretreatment. Our results indicate that the myocardial protective effects of allopurinol may differ mechanistically in the ischemic and reperfusion phases of injury. The fact that rabbit hearts do not contain detectable xanthine oxidase activity would seem to preclude an obligatory role of this enzyme both in the generation of myocardial ischemic/reperfusion injury and in the protective actions of allopurinol.
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PMID:Effects of allopurinol on myocardial ischemic injury induced by coronary artery ligation and reperfusion. 303 15

In vitro generation of free radicals by xanthine oxidase acting on hypoxanthine as a substrate induced a decreased calcium uptake velocity and reduced calcium-dependent ATPase activity of isolated sarcoplasmic reticulum (SR) vesicles from canine masseter muscle at pH 7.0. At pH 5.5 calcium uptake velocity was also reduced but ATPase activity was unaffected. Application of arachidonic acid or prostaglandin G2 induced the depression of both calcium uptake velocity and ATPase activity. The effect of arachidonic acid and prostaglandin G2 on ATPase activity depended on the pH. At pH 7.0, ATPase activity was decreased, but at pH 5.5 it was unchanged. These effects were reversed by superoxide dismutase (SOD) at pH 7.0, and by SOD plus mannitol at pH 5.5. Prostaglandin H2, prostaglandin E2 and 11,14,17-eicosatrienoic acid had no effect on calcium uptake velocity and ATPase activity at both pH 7.0 and pH 5.5. These results suggest that damage to the masseter muscle is caused by a free radical superoxide anion generated as a result of increased prostaglandins synthesis, and by the production of more lethal hydroxyl radical switched from the production of superoxide anion at low pH.
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PMID:Free radical damage to sarcoplasmic reticulum of masseter muscle by arachidonic acid and prostaglandin G2. 621 88

The effects of free-radicals generated by either the oxidation of hypoxanthine by xanthine oxidase (HX/XO) or the lipoxidation of arachidonic acid (AA) on the ATPase of the hamster cheek pouch has been studied. Cheek pouches were removed from female golden syrian hamsters and homogenized. ATPase activity was measured by the production of Pi at 37 degrees. HX/XO and AA were added at a final concentration of 9.6 X 10(-5) M HX with 5 X 10(-2) units HX and 5 X 10(-5) M AA with and without 1 X 10(-4) M ouabain. HX/XO produced a 24.7% inhibition alone and 35.0% when combined with ouabain. Ouabain alone produced a 7.1% inhibition. AA produced a 23.6% inhibition alone and 24.3% inhibition when combined with ouabain. Ouabain alone produced a 5.4% inhibition in this series. When AA was added in doses ranging from 1 X 10(-5) to 2 X 10(-3) M, a plot of percent inhibition versus log dose followed a typical sigmoid type curve. The IC50 was 1.5 X 10(-4) M. These results suggest that free-radicals are capable of inhibiting the ATPase found in the hamster cheek pouch tissues. The possible modes of action of the free-radicals in producing this inhibition are discussed.
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PMID:Free-radical inhibition of ATPase in hamster cheek pouch homogenates. 622 Jan 88

In vitro generation of free radicals by xanthine oxidase acting on xanthine as substrate depressed steady-state calcium uptake by canine cardiac sarcoplasmic reticulum vesicles. The effect of free radicals on the calcium-dependent ATPase activity of the SR vesicles was pH dependent. At pH 7.0, ATPase activity was decreased, but at pH 6.4 it was unchanged. Exposure to free radicals increased the passive permeability of the vesicles to calcium. This increase was inhibited by superoxide dismutase (SOD) at pH 7.0, and SOD plus mannitol at pH 6.4. The increased permeability per se was insufficient to explain the effects of free radicals on ATPase activity, since the calcium ionophore A23187 was unable to mimick these effects. Direct measurement of the number and turnover of the pump units indicated that the number of units was unchanged but turnover was decreased by free radicals at pH 7.0. The overall data suggest at least two mechanisms of free radical damage, one associated with an increase in passive permeability and another associated with an as yet undefined change in some specific steps of the ATPase reaction.
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PMID:Characterization of free radical-mediated damage of canine cardiac sarcoplasmic reticulum. 622 92

Effects of arachidonic acid on cellular metabolism, cation content, lipid peroxidation, sodium pump activities and release of labeled arachidonic acid were studied in C-6 glioma cells and N18TG2 neuroblastoma cells. Arachidonic acid caused a significant increase in intracellular sodium levels concomitant with a decrease in intracellular potassium in both cell lines. Both (Na+ + K+)-ATPase and p-nitrophenyl phosphatase of glioma cells were inhibited by arachidonic acid whereas only the p-nitrophenyl phosphatase of neuroblastoma cell was inactivated. Low concentrations of arachidonic acid stimulated lactic acid release whereas high concentrations had an opposite effect. In addition, the lipid peroxide content of glioma cells was increased abruptly by 50 microM arachidonic acid whereas only a slight increase of malondialdehyde was observed in neuroblastoma cells. When the cultured cells of both cell lines were incubated with exogenous labeled arachidonic acid, 78-95% of the label was incorporated into membrane phospholipids. Only a very small fraction of prostaglandin E2 and prostaglandin F2 alpha was synthesized. Exogenous arachidonic acid and free radicals generated with xanthine-xanthine oxidase caused a significant release of endogenous labeled arachidonic acid from cellular membrane phospholipids. These data further support our hypothesis that the arachidonic acid and its oxygen radical metabolites induce pathological alterations in membrane permeability and cellular volume.
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PMID:Alterations of membrane integrity and cellular constituents by arachidonic acid in neuroblastoma and glioma cells. 628 88


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