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)

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 objectives of this study were to describe the ultrastructure of granulocyte-Schistosoma mansoni egg interaction and to determine the role of reduced oxygen products as effectors of cell-mediated damage to the parasite target. Granulocytes attached to the parasites and closely applied their plasma membranes to the microspicules of the egg shell 30 min after mixing in the presence of immune serum. By 4 h, the egg shell was fractured and granulocyte pseudopodia extended toward the underlying miracidium. Granulocyte attachment to eggs resulted in release of O2- (0.30-0.52 nmol/min per 2 X 10(6) cells) and accumulation of H2O2 (0.14-0.15 nmol/min) in the presence of antibody or complement. Granulocytes reduced egg tricarboxylic-acid cycle activity and hatching by 28.3 +/- 0.9 and 35.2 +/- 2.8%, respectively (cell-egg ratio of 1,000: 1). Exogenous superoxide dismutase (10 micrograms/ml) inhibited granulocyte toxicity for egg metabolic activity (3.0 +/- 2.1% reduction in acetate metabolism vs. 28.3 +/- 0.9% decrease in controls without superoxide dismutase, P less than 0.0005) and hatching (12.5 +/- 1.8% reduction, P less than 0.0005), whereas catalase and heparin had no effect. Inhibitors of myeloperoxidase (1 mM azide, cyanide, and methimazole) augmented granulocyte-mediated toxicity of egg tricarboxylic-acid cycle activity (44-58% reduction in activity vs. 31 and 35% reduction in controls), suggesting that H2O2 released from cells was degraded before reaching the target miracidium. Oxidants generated by acetaldehyde (2 mM)-xanthine oxidase (10 mU/ml) also decreased egg metabolic activity and hatching by 62.0 +/- 9.0 and 38.7 +/- 7.3%, respectively. Egg damage by the cell-free system was partially prevented by superoxide dismutase (26.5 +/- 4.2% reduction in egg tricarboxylic-acid activity) and completely blocked by catalase (0% reduction in activity). These data suggest that granulocyte-mediated toxicity for S. mansoni eggs is dependent on release of O2- or related molecules. These oxygen products, unlike H2O2, may readily reach the target miracidium where they may be converted to H2O2 or other microbicidal effector molecules.
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PMID:Role of granulocyte oxygen products in damage of Schistosoma mansoni eggs in vitro. 298 56

Macrophage-like defence cells (haemocytes) of the pond snail Lymnaea stagnalis mediate cytotoxicity through reactive oxygen intermediates (ROIs). This activity is NADPH-oxidase dependent, as in mammalian phagocytes during the respiratory burst. In this study, mother sporocysts of schistosomes, the compatible Trichobilharzia ocellata and the incompatible Schistosoma mansoni evoke in vitro ROI activities (detected by luminol dependent chemiluminescence, LDCL) from L. stagnalis haemocytes. S. mansoni is encapsulated by haemocytes and eliminated, whereas T. ocellata escapes encapsulation and survives. Both schistosomes were equally susceptible to in vitro oxidative damage from exposure to hydrogen peroxide and to ROIs generated by a xanthine/xanthine oxidase system. Protocatechuic acid, a specific antagonist of NADPH-oxidase, delayed the killing of T. ocellata and S. mansoni sporocysts by haemocytes of resistant snails (Biomphalaria glabrata and L. stagnalis, respectively). We conclude that ROIs take part in haemocyte-mediated cytotoxicity. However, neither a snail's capability to generate ROIs, nor a schistosome's susceptibility to ROIs, determine snail/schistosome incompatibility. Snail/schistosome compatibility is rather determined by the parasite's ability to modulate haemocyte behaviour such that effective encapsulation and the generation of lethal concentrations of ROIs are prevented.
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PMID:Schistosomicidal activities of Lymnaea stagnalis haemocytes: the role of oxygen radicals. 780 Apr 16

Caffeine is increasingly used as a biochemical probe for liver function, in cancer epidemiology, and in pharmacogenetics, with its recognized ability to assess the activities of CYP1A2, xanthine oxidase, and N-acetyltransferase-2. The activity of these hepatic enzymes was tested in 45 Shona children from a rural area of Zimbabwe with use of caffeine as a probe. Many of these rural black children had lower indexes of CYP1A2 activity than otherwise on our extensive records; the average value (3.78 +/- 2.9) was significantly (p < 0.001) lower than that of healthy white urban children from Zimbabwe (8.86 +/- 3.36) or from Canada (7.92 +/- 1.88), or that of healthy Canadian adults (5.96 +/- 2.4). A higher CYP1A2 activity in children than in adults is usual. The low CYP1A2 activity of the children from rural Zimbabwe calls for medical studies and suggests a widespread and perhaps serious impairment of certain liver functions. Causes could be parasitic infections with Schistosoma mansoni, causing schistosomiasis, which are endemic, in addition to generally poor nutrition and frequent iodine deficiency. By contrast, the xanthine oxidase activity in rural Shona children was slightly higher than that reported for a healthy Canadian adult population. The N-acetyltransferase activities were comparable in both the rural and urban children and were also similar to those reported in a population study of healthy adult Canadians.
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PMID:Low CYP1A2 activity in rural Shona children of Zimbabwe. 782 78

The levels of superoxide dismutase (SOD) were determined in detergent-soluble, somatic and excretion-secretion (E-S) preparations from adult Fasciola hepatica using the xanthine oxidase system and visualized in substrate gels. Compared to detergent-soluble and somatic extracts, E-S products showed the highest SOD activity (88.5 U/mg), indicating active release to the medium in which parasites were maintained. SOD specific activity was also detected at high levels in E-S products from 3-week-old and 5-week-old immature migrating flukes (25 and 143 U/mg, respectively). In all preparations except for the somatic extract, the activity was characterized as cyanide-sensitive CuZn SOD. Differences in SOD isoenzyme profiles between the extracts were observed in native polyacrylamide gel electrophoresis: the somatic and detergent-soluble extracts exhibited 1 band of activity while the E-S products from immature and adults flukes contained 2 and 3 migrating bands, respectively. SOD was purified from the detergent-soluble extract and E-S products of adult worms by a combination of ultrafiltration, gel filtration on Sephacryl S-200 HR and ion-exchange chromatography on QAE Sephadex A-50. The SOD from detergent-soluble extract showed, by SDS-PAGE analysis, 1 band of 16 kDa apparent molecular weight. The SOD from E-S products showed 2 bands of 16 and 60 kDa apparent molecular weight. N-terminal sequence analysis of the 16 kDa band from the detergent-soluble preparation showed some similarity with Schistosoma mansoni cytoplasmic SOD. These enzymes may have a potential role in the evasion of the oxidative burst killing mechanism by immune cells.
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PMID:CuZn superoxide dismutase activities from Fasciola hepatica. 988 80

Free radicals have previously been shown to kill the immature stages of the trematode, Schistosoma mansoni but their effect on newly excysted juvenile (NEJ) flukes of Fasciola hepatica has not been established. Using acetaldehyde and xanthine oxidase to chemically generate reactive oxygen intermediates (ROI), up to 61% of NEJ were killed but only when exposed to high levels of ROI. At low concentrations of acetaldehyde and xanthine oxidase as sources of reactive oxygen intermediates, only 6-29% of NEJ were killed compared with 70-92% of schistosomula. Incubation with lipopolysaccharide (LPS)-stimulated rat peritoneal lavage cells (PLCs) killed only 7-15% of NEJ whereas 78-87% of schistosomula were killed under the same conditions by a mechanism dependent on the production of reactive nitrogen intermediates. Relative to immature and adult parasites, NEJ expressed 2.5-20-fold lower levels of superoxide dismutase and glutathione S-transferase but no catalase activity was detected. Incubation of NEJ with inhibitors of peroxidases and glutathione metabolism increased the mean killing of NEJ by LPS-stimulated rat PLCs to 40-75%. These results demonstrate that, in comparison to schistosomula of S. mansoni, NEJ of F. hepatica are relatively resistant to killing by free radicals and this resistance could, in part, be due to the activity of oxidant scavenger enzymes of NEJ.
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PMID:Juvenile Fasciola hepatica are resistant to killing in vitro by free radicals compared with larvae of Schistosoma mansoni. 1084 8

Killing of intramolluscan schistosomes by host haemocytes is mediated by reactive oxygen metabolites. Hence, defence against oxidative damage is essential for the parasite to survive. In this study, expression of three key antioxidant enzymes, superoxide dismutase (EC 1.15.1.1), glutathione peroxidase (EC 1.11.1.9) and glutathione-S-transferase (EC 2.5.1.18) was determined in Schistosoma mansoni miracidia, sporocysts and cercariae. Stage-dependent expression of these enzymes was shown to be regulated at the transcriptional level. Second, the influence on enzyme expression of reactive oxygen species (ROS) and of haemocytes from schistosome-resistant and -susceptible host snails was determined. Generation of ROS by xanthine/xanthine oxidase resulted in increased transcript levels for all three enzymes. Addition of hydrogen peroxide induced a significantly increased expression of GPx and SOD but not GST. Snail haemocytes induced an up-regulation of SOD and GPx at 12 and 18 h post-exposure, respectively. Susceptible haemocytes elicited a stronger induction of transcript expression than resistant haemocytes. After 36-48 h, SOD remained up-regulated in sporocysts encapsulated by haemocytes from susceptible hosts, whereas a down-regulation of SOD and GPx occurred in schistosomes encapsulated by haemocytes from resistant snails. These observations indicate that schistosomes express elevated levels of antioxidant enzymes in interaction with haemocytes from susceptible snail hosts in which they survive. On the other hand, haemocytes of resistant snails may interfere with reactive oxygen detoxification via down-regulation of schistosome antioxidant enzymes, thus shifting the balance towards parasite killing.
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PMID:Antioxidant enzymes in intramolluscan Schistosoma mansoni and ROS-induced changes in expression. 1518 Mar 17