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)

Adult worms of Acanthocheilonema viteae were found to be susceptible to the reactive oxygen intermediates (ROI) generated by the xanthine-xanthine oxidase (X-XO) system. The damage caused by this system was completely abolished by superoxide dismutase (SOD) and catalase but not by mannitol. The results, therefore, suggest that superoxide anions (O2-) and hydrogen peroxide (H2O2) alone or in combination might be toxic to the filariid. A. viteae exhibited the presence of an active enzyme system to protect itself against the oxidants. SOD and catalase were present in high levels of activities and appeared to constitute the major defence system. The role of glutathione peroxidase (GPx), on the other hand, seemed less important due to the weak activities of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH). A. viteae also released SOD, catalase and GPx in the ambient medium, which appear useful in protecting the filariid against ROI generated by the host in the immediate surroundings of the parasite. Antifilarial agents, diethylcarbamazine (DEC) and 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone (82/437) appreciably inhibited catalase and GPx of A. viteae. Inhibition of these enzymes appears to render the parasite prone to H2O2 toxicity leading to death. No adverse effect on antioxidant enzymes of liver, lungs and subcutaneous tissue of Mastomys natalensis recorded as a result of exposure to 82/437 suggests a non-toxic nature to the compound.
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PMID:Antioxidant enzymes in Acanthocheilonema viteae and effect of antifilarial agents. 224 37

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

Adult worms of Ancylostoma ceylanicum and Nippostronglyus brasiliensis were found to possess an active system for the detoxification of reactive oxygen intermediates. Xanthine oxidase, which is known to produce superoxide anion, was detected in both the nematode parasites in significant activities. Superoxide anion, thus produced, may quickly be eliminated by superoxide dismutase. Both parasites also exhibited the presence of catalase, peroxidase, and glutathione peroxidase for efficient removal of hydrogen peroxide. Glutathione reductase and glucose-6-phosphate dehydrogenase were, however, detected in low levels of activities. Endowment of A. ceylanicum and N. brasiliensis with these antioxidant enzymes, therefore, enables them to evade the host's effector mechanism for their survival. Superoxide dismutase of both these nematodes showed marked inhibition by KCN and, hence, the enzyme appears to be of copper-zinc type.
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PMID:Reactive oxygen intermediates metabolizing enzymes in Ancylostoma ceylanicum and Nippostrongylus brasiliensis. 234 Oct 58

In order to understand why different stages of Trichinella spiralis vary in their susceptibility to killing by leukocytes, the effects of artificially generated oxidants on different stages of this parasite were compared. More than 90% newborn larvae were killed after incubation in acetaldehyde-xanthine oxidase or glucose-glucose oxidase. On the other hand, fewer than 10% of adult worms or muscle larvae were killed when incubated under identical conditions. Thus, only the stages which are resistant to killing by leukocytes are resistant to killing by oxidants. The larvicidal effect of acetaldehyde-xanthine oxidase was blocked by the addition of either superoxide dismutase or catalase and was partially inhibited by radical scavengers and singlet oxygen quenchers. The oxidant resistant adults and muscle larvae contained 3-5 times more superoxide dismutase and at least five times more glutathione peroxidase than the oxidant sensitive newborn larvae. In contrast, all 3 stages lacked detectable amounts of catalase and contained roughly equivalent amounts of reduced glutathione. Accordingly, adults and muscle larvae may be more resistant to killing by leukocytes than newborn larvae because they contain better oxidant defenses.
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PMID:Scavenger enzymes and resistance to oxygen mediated damage in Trichinella spiralis. 669 69

The presence of superoxide dismutase (SOD) activity in the bovine lungworm Dictyocaulus viviparus was examined using the xanthine-xanthine oxidase assay system and by non-denaturing PAGE followed by specific enzyme staining. High levels of activity were detected in excretory-secretory (ES) products of adult worms and in soluble extracts of both the L3 and adult stages of the parasite. Stage-specific and ES-specific activities were indicated by differences in SOD isoenzyme profiles between adult and larval parasite extracts and between adult extract and ES products, with a fast migrating activity being specific to ES products. All isoenzymes were sensitive to cyanide, indicating copper/zinc dependency. The antigenicity of ES SOD was demonstrated by a reduction in SOD activity in both the chemical assay and non-denaturing PAGE following incubation of parasite ES products with IgG antibody purified from serum of infected or vaccinated bovine hosts. The high level of SOD activity released by adult D. viviparus may be a reflection of the problems faced by a parasite occupying an oxygen-rich environment. Antibody inhibition of SOD may, therefore, be an important target of protective immunity.
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PMID:Superoxide dismutase (SOD) activity of Dictyocaulus viviparus and its inhibition by antibody from infected and vaccinated bovine hosts. 808 70

To understand the mechanism for the expulsion of Nippostrongylus brasiliensis from rats, age-dependent variations in the metabolism of reactive oxygen species in the parasite and the host intestines were examined. N. brasiliensis showed an age-dependent increase in its susceptibility to xanthine-xanthine oxidase and t-butyl hydroperoxide generated oxidants as well as to H2O2. Protection obtained with several scavengers suggested that the worms were damaged by the combined action of oxidants generated by the in vitro systems employed. The level of superoxide dismutase in the nematode and its release into the surroundings exhibited a marked depression with advancement of age. No such alteration was, however, recorded for catalase and glutathione peroxidase. An appreciable decrease in the level of reduced glutathione in older N. brasiliensis appears to render them prone to oxidant attack. The rat intestines, on the other hand, exhibited an appreciable depression in catalase and a reduced glutathione content with progress of the infection. Vitamin E levels were elevated. The release of O2-. and H2O2 by the intestines was also found to be greater during later stages of the infection. The combined effect of the changes observed in N. brasiliensis and in the rat intestines may be at least partly responsible for expulsion of the nematode from the rats after day 10.
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PMID:Role of reactive oxygen species in expulsion of Nippostrongylus brasiliensis from rats. 838 14

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

EPR spectrometry was used to investigate the effect of excretory/secretory product from Necator americanus on superoxide radical anions generated by xanthine/xanthine oxidase as a measure of excretory/secretory product superoxide dismutase activity. Using 1,1',5,5'-dimethylpyrollidine-N-oxide (DMPO) as a superoxide spin-trapping agent a 12-line EPR spectrum characteristic of the DMPO-OOH adduct was observed to decrease in the presence of excretory/secretory product. Superoxide dismutase activity was proportional to excretory/secretory protein concentration, was inhibited with cyanide treatment and was progressively destroyed with increasing time of heat denaturation of excretory/secretory product. Using a purpose-built chamber the superoxide dismutase activity of excretory/secretory product from live worms in culture was shown to accumulate with time to a maximum at 4 h. The electron paramagnetic resonance spectrum obtained for the frozen excretory/secretory product of N. americanus recorded at 77 K is typical of Cu(II) in a protein matrix. The results are consistent with the presence of an active Cu/Zn superoxide dismutase in excretory/secretory product from N. americanus and demonstrate a method for the unequivocal determination of the fate of superoxide anions in the presence of live worms.
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PMID:Cu/Zn superoxide dismutase in excretory-secretory products of the human hookworm Necator americanus. An electron paramagnetic spectrometry study. 1049 Oct 88

The ability of oxygen radicals to kill Heligmosomoides polygyrus adult worms was examined by assessing parasite survival following incubation with hydrogen peroxide and acetaldehyde/xanthine oxidase, generators of H2O2 and H2O2/O2(-), respectively. H. polygyrus worms could tolerate levels of < 0.25 mM hydrogen peroxide and < 0.5 mM/20 mU acetaldehyde/xanthine oxidase for 20 h, but, at higher concentrations, marked sex-dependent susceptibility was observed, with males being more sensitive to H2O2 and O2(-) than female worms. The ability to evade free radical-mediated damage was also evaluated by measuring superoxide dismutase (SOD) and catalase levels in worms isolated at different time points from four strains of mice with differing resistance phenotypes. Levels of both catalase and SOD in female worms isolated from 'rapid'[(SWRxSJL)F1], 'fast' (SWR) or 'intermediate' (BALB/c), but not 'slow' (C57BL/10), responder mice showed a strain-dependent increase with time. Moreover, male worms were rejected faster than female worms in the 'rapid', 'fast' and 'intermediate' responder strains of mice. The results suggest that host-derived free radicals can damage adult worms and that female worms can increase production of their scavenging enzymes in response to the immune onslaught that eventually leads to worm expulsion in mice with 'fast', 'rapid' or 'intermediate' response phenotypes.
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PMID:Effect of oxygen radicals and differential expression of catalase and superoxide dismutase in adult Heligmosomoides polygyrus during primary infections in mice with differing response phenotypes. 1198 57

This study examined the genomic organisation of the coding region of the glutathione S-transferase 3 (Ov-GST-3) from the human parasitic nematode Onchocerca volvulus; alternative splicing leads to three different transcripts (Ov-GST-3/1; Ov-GST-3/2 and Ov-GST-3/3). Since the expression of Ov-GST-3 is inducible by oxidative stress, it is assumed that it is involved in the defense against reactive oxygen species (ROS) resulting from cellular metabolism. Furthermore, we suggest that Ov-GST-3 plays an important role in the protection of the parasite against ROS derived from the host's immune system. To experimentally investigate these speculations, we generated Caenorhabditis elegans lines transgenic for Ov-GST-3 (AK1) and examined their resistance to artificially generated ROS. The AK1 worms (extrachromosomal and integrated lines) were found to be much more resistant to internal (juglone) and external (hypoxanthine/xanthine oxidase) oxidative stress than wild-type C.elegans worms. RNA interference experiments targeted to the Ov-GST-3 transcripts resulted in decreased resistance, confirming that this effect is due to the transgenic expression of Ov-GST-3. These results clearly demonstrate that the Ov-GST-3 gene confers an increased resistance to oxidative stress. This study also shows the applicability of C.elegans as a model organism for the functional characterization of genes from (parasitic) nematode species which are not accessible to genetic manipulations.
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PMID:Functional analysis of the glutathione S-transferase 3 from Onchocerca volvulus (Ov-GST-3): a parasite GST confers increased resistance to oxidative stress in Caenorhabditis elegans. 1247 50


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