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)

Brain ischemia reperfusion causes increased formation of reactive oxygen species (ROS). Activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) has been shown to undergo a significant decrease following reperfusion of the ischemic tissue. We have examined the effect of a superoxide radical-generating system (xanthine oxidase/hypoxanthine, XO/HX) on the activity of this enzyme. Incubation of PDH in the presence of XO/HX resulted in its inactivation. The degree of the inactivation was dependent on the amount of XO present, which correlated linearly with the concentration of superoxide radical generated by this system. The activity of lactate dehydrogenase, an enzyme resistant to inactivation by ischemia reperfusion, was not affected by this system. Superoxide dismutase partially prevented and catalase exerted a nearly complete protective effect against the inactivation of PDH. Deferoxamine was partially protective. The sulfhydryl protective reagents, dithiothreitol and glutathione, prevented the inactivation of PDH, even though to varying degrees, which implicates sulfhydryl oxidation. A hydroxyl radical-generating system (hydrogen peroxide irradiated with ultraviolet radiation) effectively inactivated PDH. These results demonstrate that PDH is susceptible to damage and inactivation by ROS and point to the involvement of Fenton chemistry and hydroxyl radicals formed through it in PDH inactivation by XO/HX. A similar mechanism may be responsible for the PDH inactivation during ischemia/reperfusion.
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PMID:Reactive oxygen species-mediated inactivation of pyruvate dehydrogenase. 895 77

Apoptosis is a distinct form of cell death that is observed under various physiologic and pathologic conditions, and it is thought to be important in regulating the number of glomerular cells. This study investigated the possible role of reactive oxygen species in the induction of apoptosis in cultured human mesangial cells. Fragmented nuclei with condensed chromatin, a morphologic characteristic of apoptosis, were observed by electron microscopy in mesangial cells exposed to 0.02 mM hydrogen peroxide for 4 h. Nuclear DNA extracted from mesangial cells that had been incubated with hydrogen peroxide (2 to 20 mM) or with xanthine (0.05 mM) and xanthine oxidase (5 to 100 mU/mL) showed the ladder pattern on electrophoresis that is a biochemical marker for apoptosis. Hydrogen peroxide (0.02 to 20 mM) decreased the number of viable cells, as determined by trypan blue exclusion, in a dose-dependent manner. Hydrogen peroxide or xanthine and xanthine oxidase increased the lactate dehydrogenase release from mesangial cells in a dose- and time-dependent manners. The release of lactate dehydrogenase was prevented by treatment with a free radical scavenger, catalase. Hydrogen peroxide (2 mM) also significantly increased the number of mesangial cells with fragmented DNA as detected by in situ nick end-labeling Results indicate that reactive oxygen species induce apoptosis in cultured human mesangial cells. Furthermore, apoptosis of mesangial cells induced by reactive oxygen species may contribute to the loss of such cells observed in glomerular disease.
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PMID:Reactive oxygen species induce apoptosis in cultured human mesangial cells. 895 25

The effects of hypoxia of different durations (8, 12 or 15 min) and of subsequent reoxygenation were studied in rat hippocampal slices by measuring enzyme activities related to oxidative stress: superoxide dismutase (SOD), cytochrome c oxidase and lactate dehydrogenase (LDH). Simultaneously the degree of lipid peroxidation was estimated by measuring conjugated dienes (CD). Reoxygenation after 8-min of hypoxia induced general cell injury indicated by increased LDH activity. Reoxygenation after 12-min of hypoxia started lipid peroxidation assessed by an increase in CD, and after 15-min of hypoxia followed by reoxygenation CD were found to be significantly decreased, suggesting lipid degradation. The injury induced by a hypoxia of 12 min and reoxygenation was reduced by SOD and catalase, indicating that oxygen radicals were involved in this process. The oxygen radicals originating from the xanthine/xanthine oxidase system, from the synthesis of prostaglandins, as well as from the mitochondrial respiratory chain, since allopurinol, indomethacin and rotenone decreased while antimycin increased reoxygenation injury. An increase in ATP may also have been involved as cyanide, an inhibitor of ATP synthesis, decreased the reoxygenation injury. The chain-breaking antioxidants trolox, alpha tocopherol and the pyridoindole stobadine were effective in preventing reoxygenation injury, indicating the involvement of lipid peroxidation in this process.
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PMID:Mechanisms of hippocampal reoxygenation injury. Treatment with antioxidants. 914 55

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

Among progeny of a hybrid (Rana shqiperica x R. lessonae) x R. lessonae, 14 of 22 loci form four linkage groups (LGs): (1) mitochondrial aspartate aminotransferase, carbonate dehydratase-2, esterase 4, peptidase D; (2) mannosephosphate isomerase, lactate dehydrogenase-B, sex, hexokinase-1, peptidase B; (3) albumin, fructose-biphosphatase-1, guanine deaminase; (4) mitochondrial superoxide dismutase, cytosolic malic enzyme, xanthine oxidase. Fructose-biphosphate aldolase-2 and cytosolic aspartate aminotransferase possibly form a fifth LG. Mitochondrial aconitate hydratase, alpha-glucosidase, glyceraldehyde-3-phosphate dehydrogenase, phosphogluconate dehydrogenase, and phosphoglucomutase-2 are unlinked to other loci. All testable linkages (among eight loci of LGs 1, 2, 3, and 4) are shared with eastern palearctic water frogs. Including published data, 44 protein loci can be assigned to 10 of the 13 chromosomes in Holarctic Rana. Of testable pairs among 18 protein loci, agreement between Palearctic and Nearctic Rana is complete (125 unlinked, 14 linked pairs among 14 loci of five syntenies), and Holarctic Rana and Xenopus laevis are highly concordant (125 shared nonlinkages, 13 shared linkages, three differences). Several Rana syntenies occur in mammals and fish. Many syntenies apparently have persisted for 60-140 x 10(6) years (frogs), some even for 350-400 x 10(6) years (mammals and teleosts).
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PMID:Linkage groups of protein-coding genes in western palearctic water frogs reveal extensive evolutionary conservation. 928 85

The aim of this study was to determine whether the administration of free radical antagonists, immediately before and during the early minutes of reperfusion, improves muscle survival 24 hr after a period of ischemia. Rabbit rectus femoris muscles were isolated, made ischemic for 3 1/2 hr and treated with either desferrioxamine (DFX), an Fe3+ chelator, superoxide dismutase and catalase (SOD & CAT), which quench superoxide and hydrogen peroxide, or allopurinol, an inhibitor of xanthine oxidase (XO). After 24 hr reperfusion, muscle viability (+/-s.e.m.), measured by the nitro blue tetrazolium (NBT) vital staining technique, was 41.6 +/- 11.3% for saline-treated ischemic controls, 30.6 +/- 7.6% for DFX-treated, 46.7 +/- 10.3% for SOD & CAT-treated, and 43.3 +/- 9.5% for allopurinol-treated muscles. None of the treated groups differed significantly from the ischemic control group. Tissue myeloperoxidase, ATP and reduced glutathione levels, and plasma lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels were increased by ischemia and reperfusion in all groups, but the changes did not differ between the treatment groups. Levels of XO in the rabbit muscle were determined and found to be very low in both normal and postischemic muscle. As XO is the target enzyme of allopurinol, its absence provides a basis for the lack of effect of this agent. However, it is not clear why DFX and SOD & CAT had no protective effect.
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PMID:Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle. 939 70

Three strains of human diploid fibroblasts, TIG-3, TIG-7, and MRC-5, were serially cultivated. The susceptibility of early-passage and late-passage cells at 20-30 and 60-70 population doubling levels, respectively, to hydrogen peroxide, the superoxide radical (exposure to the hypoxanthine-xanthine oxidase system), or linoleic acid hydroperoxide was examined for lactate dehydrogenase release. The susceptibility of late-passage cells to such oxidative stress was considerably enhanced compared with early-passage cells. The concentration of reduced glutathione in late-passage cells was lower by 24-44% on a per-cell-number basis and by 86.0-94.5% on a per-protein-quantity basis than in early-passage cells. In addition, the activity of catalase in late-passage cells was lower by 19-46% compared with early-passage cells. There was, however, no difference between the mRNA levels of catalase in early-passage and late-passage cells. The activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase, and glutathione peroxidase in late-passage cells were all higher than in early-passage cells. These results suggest that late-passage cells are more susceptible to oxidative stress than early-passage cells presumably because of decreases in cellular reduced glutathione concentration and catalase activity, and that their primary defense against oxidative stress is reduced glutathione.
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PMID:Increased susceptibility of late passage human diploid fibroblasts to oxidative stress. 941 4

The unique anti-oxidative activity of nitroxide radicals protecting against reactive oxygen-derived species (ROS) has been recently demonstrated in several model systems. The present study focuses on the activity of nitroxide and of its reduced form in cultured rat ventricular cardiomyocytes exposed to O2.- and H2O2 generated by hypoxanthine (HX) and xanthine oxidase (XO). To evaluate cell injury, spontaneous beating, leakage of lactate dehydrogenase (LDH), and depletion of cellular ATP were determined. The protective effect of 4-OH-2,2,6,6-tetramethyl-piperidine-N-oxyl (TPL) was compared with that of 4-OH-2,2,6,6-tetramethyl-1-hydroxypiperidine (TPL-H) and of several common anti-oxidants. A rapid exchange between TPL and TPL-H, is mediated by cellular metabolism and through reactions with ROS. In particular, TPL under O2.- flux is oxidized to oxo-ammonium cation (TPL+) which comproportionates with TPL-H yielding two nitroxide radicals. Because this exchange limits the distinction between the biological activities of TPL and TPL-H, NADH which can reduce TPL+ was included in order to maintain the nitroxide in its reduced form. The results demonstrate that both TPL and TPL-H protect cardiomyocytes against beating loss and LDH leakage. Conversely, cellular ATP depletion induced by HX/XO is inhibited by TPL-H, though not by TPL, suggesting that different mechanisms underlie their protective activities. Through a flip-flop between the two forms, which coexist in the system, the levels of TPL-H and TPL are continuously replenished. The conversion, upon reaction, of each antioxidant into the other one enables them, contrary to common antioxidants which operate in a stoichiometric mode, to act catalytically.
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PMID:Both hydroxylamine and nitroxide protect cardiomyocytes from oxidative stress. 943 15

Reactive free radical species appear to be involved in the ischemic injury of cardiac muscle, although the mechanisms by which oxygen-derived free radicals affect the heart cell function are not known. In the present study, cultured ventricular myocytes were exposed to an exogenous oxygen radical generating system. The myocyte-enriched, primary cultures were prepared from ventricles of new-born rat heart and exposed to a xanthine/xanthine oxidase (X+XO) system. The transmembrane potentials were recorded with glass microelectrodes. Cell contractions were monitored photometrically. The release of lactate dehydrogenase (LDH) in the medium was analysed. Quantitative measurement and the time course of the radical generation were performed by the electron paramagnetic resonance (EPR) spin trapping technique with the spin trap 5,5-dimethyl-1-pyroline-N-oxide (DMPO). We verified that X and XO alone had no significant functional and biochemical effects. The X+XO system produced a rapid decrease in the action potential amplitude. This effect was accompanied by a strong decrease in contractility and spontaneous rate. The time course of these functional defects were correlated with a progressive efflux of LDH from the cardiomyocytes. Prolonging the exposure to the X+XO system provoked the cessation of the spontaneous beatings and the progressive loss of the resting diastolic potential, together with a near total release of the cellular LDH. The LDH release and the functional depression were both efficiently prevented by catalase. On the contrary, superoxide dismutase (SOD) slowed down but did not protect against the functional and biochemical effects of the free radicals. In comparison, the EPR spectra obtained indicated that the X+XO system was associated with an important generation of superoxide anions but also with a small hydroxyl production. SOD scavenged the superoxide but a small .OH production persisted. Catalase (CAT) did not modify the superoxide generation but decreased the hydroxyl adduct formation. These results suggest that, although the generation of superoxide anions by the X+XO system was higher than the hydroxyl production, the functional injury and enzyme leakage seemed mainly mediated through a hydrogen peroxide-hydroxyl radical pathway. Cultured ventricular myocytes can be thus used as a valuable model to investigate the cellular mechanism of oxidant-induced damage in the heart.
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PMID:Correlation between direct ESR spectroscopic measurements and electromechanical and biochemical assessments of exogenous free radical injury in isolated rat cardiac myocytes. 943 21

Dried flower extracts of Hibiscus sabdariffa L., a local soft drink material and medical herb, was found to possess antioxidant activity in the present study. In the preliminary studies, antioxidant potential of three fractions of the ethanol crude extract (HS-C: chloroform-soluble fraction; HS-E: ethyl acetate soluble fraction; HS-R: residual fraction) obtained from the dried flowers of Hibiscus sabdariffa L. were evaluated by their capacity of quenching 1,1 -diphenyl-2-picrylhydrazyl (DPPH) free radical and inhibiting xanthine oxidase (XO) activity. HS-E showed the greatest capacity of scavenging free radical (EC50=0.017mg/ml), and HS-C showed the strongest inhibitory effect on XO activity (EC5o=0.742 mg/ml). Furthermore, antioxidant bioactivities of these crude extracts were investigated using a model of tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in rat primary hepatocytes. All fractions were found to inhibit significantly the unscheduled DNA synthesis (UDS) induced by t-BHP at a concentration of 0.20 mg/ml. HS-C and HS-E also decreased the leakage of lactate dehydrogenase (LDH) and the formation of malondialdehyde (MDA) induced by t-BHP (1.5 mM) considerably at a concentration of 0.10 and 0.20 mg/ml in the rat primary hepatocyte cultures. These results indicated that the dried flower extracts (HS-C and HS-E) of H. sabdariffa L. protect rat hepatocytes from t-BHP-induced cytotoxicity and genotoxicity by different mechanisms.
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PMID:Protective effects of dried flower extracts of Hibiscus sabdariffa L. against oxidative stress in rat primary hepatocytes. 944 21


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