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

---

Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UVB irradiation augmented the beta-adrenergic adenylate cyclase response of pig skin epidermis in vitro. The effect was observed 2-4 h following the irradiation and lasted at least for 48 h. There was no significant difference in cyclic AMP phosphodiesterase activity between control and UVB-irradiated epidermis at lower irradiation dose (150 mJ/cm2), which is the dose of the most marked beta-adrenergic augmentation effect. The augmentation effect was specific to the beta-adrenergic system; adenosine and histamine adenylate cyclase responses were unchanged or decreased depending on the irradiation dose. Histologically, marked sunburn-cell formation was observed following the UVB irradiation. It has been suggested that oxygen intermediates generated by ultraviolet radiation participate in sunburn-cell formation. The addition of superoxide dismutase (SOD) in the incubation medium significantly inhibited sunburn-cell formation. On the other hand, the beta-adrenergic augmentation effect was not affected by the addition of SOD. Other scavengers of oxygen intermediates (catalase, catalase + SOD, xanthine, or mannitol) did not inhibit the UVB-induced beta-adrenergic augmentation effect. Further, superoxide-anion generating systems (hypoxanthine-xanthine oxidase system and acetaldehyde-xanthine oxidase system) revealed no stimulatory effect on the beta-adrenergic response of epidermis. These results indicate that (a) the UVB-induced beta-adrenergic augmentation effect is inherent to skin and does not depend on systemic factors such as inflammatory infiltrates following UVB irradiation; (b) in contrast to sunburn-cell formation, induction of the beta-adrenergic adenylate cyclase response is not directly associated with oxygen intermediates generated by UVB irradiation.
...
PMID:Effects of UVB irradiation on epidermal adenylate cyclase responses in vitro: its relation to sunburn cell formation. 289 32

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.
...
PMID:Role of granulocyte oxygen products in damage of Schistosoma mansoni eggs in vitro. 298 56

Group B streptococci (GBS) lack catalase, and they produce and release H2O2;thus, they should be readily killed by phagocytes with a diminished respiratory burst. Surprisingly, although strains of Staphylococcus aureus were killed at H2O2 concentrations greater than 0.5 mM, GBS strains were killed only at concentrations greater than 5mM. In contrast, GBS were killed by hydroxyl radicals generated by the xanthine oxidase-acetaldehyde system at O2 fluxes greater than or equal to 3.5 nmol/ml per min, whereas O2 fluxes greater than or equal to 10 nmol/ml per min were required to kill the S. aureus strains. Results with virulent and laboratory strains of GBS were similar. The differences in susceptibility of GBS and S. aureus seemed to correlate with differences in content of endogenous oxygen-metabolite scavengers. GBS contained approximately 100-fold more glutathione and approximately 20-fold more glutathione reductase than did S. aureus, whereas S. aureus was rich in catalase that GBS lacked. GBS that were grown in buthionine sulfoximine, however, contained 87% less glutathione than did controls but were not more susceptible to killing by H2O2 or the xanthine oxidase-acetaldehyde system. Similarly, the relative susceptibility of GBS to tert-butyl hydroperoxide and H2O2 paralleled that of S. aureus. Thus, inherent differences in susceptibility of vital cellular functions to oxidative damage rather than content of oxygen-metabolite scavengers may account for the differences in susceptibility of GBS and S. aureus.
...
PMID:Comparative susceptibility of group B streptococci and Staphylococcus aureus to killing by oxygen metabolites. 299 35

Human neutrophils (PMN), when stimulated with such chemotaxins as phorbol myristate acetate (PMA), destroy erythrocytes and other targets. Cytotoxicity depends on PMN-generated reactive oxygen metabolites, yet the exact toxic specie and its mode of production is a matter of some dispute. Using 51Cr-labeled erythrocytes as targets, we compared various reactive-O2 generating systems for their abilities to lyse erythrocytes as well as to oxidize hemoglobin to methemoglobin. PMA-activated PMNs or xanthine oxidase plus acetaldehyde were added to target erythrocytes in amounts that provided similar levels of superoxide. PMNs lysed 68.3 +/- 2.9% (SEM) of targets, whereas the xanthine oxidase system was virtually impotent (2.3 +/- 0.8%). In contrast, methemoglobin formation by xanthine oxidase plus acetaldehyde was significantly greater than that caused by stimulated PMNs (P less than 0.001). A similar dichotomy was noted with added reagent H2O2 or the H2O2-generating system, glucose plus glucose oxidase; neither of these caused 51Cr release, but induced 10-70% methemoglobin formation. Thus, although O2- and H2O2 can cross the erythrocyte membrane and rapidly oxidize hemoglobin, they do so evidently without damaging the cell membrane. That a granule constituent of PMNs is required to promote target cell lysis was suggested by the fact that agranular PMN cytoplasts (neutroplasts), although added to generate equal amounts of O2- as intact PMNs, were significantly less lytic to target erythrocytes (P less than 0.01). Iron was shown to be directly involved in lytic efficiency by supplementation studies with 2 microM iron citrate; such supplementation increased PMN cytotoxicity by approximately 30%, but had much less effect on erythrocyte lysis by neutroplasts (approximately 3% increase), and no effect on lysis in the enzymatic oxygen radical-generating systems. These results suggest a critical role for an iron-liganding moiety that is abundantly present in PMN, marginally so in neutroplasts, and not at all in purified enzymatic systems--a moiety that we presume catalyzes very toxic O2 specie generation in the vicinity of juxtaposed erythrocyte targets. The obvious candidate is lactoferrin (LF), and indeed, antilactoferrin IgG, but not nonspecific IgG, reduced PMN cytotoxicity by greater than 85%. Re-adding 10(-8) M pure LF to neutroplasts increased their ability to promote hemolysis by 48.4 +/- 0.9%--to a level near that of intact PMNs. We conclude that O-2 and H2O2 are not sufficient to mediate target cell lysis, but require iron bound to LF, which, in turn, probably generates and focuses toxic O2 radicals, such as OH, to target membrane sites.
...
PMID:Oxygen radical-induced erythrocyte hemolysis by neutrophils. Critical role of iron and lactoferrin. 299 52

Active oxygen species are suspected as being a cause of the cellular damage that occurs at the site of inflammation. Phagocytic cells accumulate at these sites and produce superoxide ion, hydrogen peroxide and hydroxyl radical. The ultimate killing species, the cellular target and the mechanism whereby the lethal injury is produced are unknown. We exposed mouse fibroblasts to xanthine oxidase and acetaldehyde, a system which mimics the membrane of phagocytic cells in terms of production of oxygen species. We observed that the generation of these species produced DNA strand breaks and cellular death. The metal chelator o-phenanthroline completely abolished the former effect, and at the same time it effectively protected the cells from lethal injuries. Because complexing iron o-phenanthroline prevents the formation of hydroxyl radical by the Fendon reaction (Fe(II) + H2O2----Fe(III) + OH- + OH.), it is proposed that most of the cell death and DNA damage are brought about by OH radical, produced from other species by iron-mediated reactions.
...
PMID:Protection of mammalian cells by o-phenanthroline from lethal and DNA-damaging effects produced by active oxygen species. 299 16

The univalent and divalent reductions of dioxygen were measured using lumazine as a low turnover substrate and both xanthine and acetaldehyde as high turnover substrates. These measurements were made in solutions equilibrated with air and with 100% O2. The univalent route of dioxygen reduction predominated with the low turnover substrate and was increased by raising pO2 and by lowering substrate concentration. These results support the view that electron egress from heavily reduced xanthine oxidase occurs by divalent transfers, while that from the partially reduced enzyme is by univalent transfers. Xanthine oxidase, acting as lumazine, is a convenient source of O2-.
...
PMID:Superoxide radical from xanthine oxidase acting upon lumazine. 301 70

Xanthine oxidase is able to mobilize iron from ferritin. This mobilization can be blocked by 70% by superoxide dismutase, indicating that part of its action is mediated by superoxide (O2-). Uric acid induced the release of ferritin iron at concentrations normally found in serum. The O2(-)-independent mobilization of ferritin iron by xanthine oxidase cannot be attributed to uric acid, because uricase did not influence the O2(-)-independent part and acetaldehyde, a substrate for xanthine oxidase, also revealed an O2(-)-independent part, although no uric acid was produced. Presumably the amount of uric acid produced by xanthine oxidase and xanthine is insufficient to release a measurable amount of iron from ferritin. The liberation of iron from ferritin by xanthine oxidase has important consequences in ischaemia and inflammation. In these circumstances xanthine oxidase, formed from xanthine dehydrogenase, will stimulate the formation of a non-protein-bound iron pool, and the O2(-)-produced by xanthine oxidase, or granulocytes, will be converted by 'free' iron into much more highly toxic oxygen species such as hydroxyl radicals (OH.), exacerbating the tissue damage.
...
PMID:Superoxide-dependent and -independent mechanisms of iron mobilization from ferritin by xanthine oxidase. Implications for oxygen-free-radical-induced tissue destruction during ischaemia and inflammation. 302 67

Evidence in alcoholics as well as in experimental models support the role of hepatic lipid peroxidation in the pathogenesis of alcohol-induced liver injury, but the mechanism of this injury is not fully delineated. Previous studies of the metabolism of ethanol by alcohol dehydrogenase revealed iron mobilization from ferritin that was markedly stimulated by superoxide radical generation by xanthine oxidase. Peroxidation of hepatic lipid membranes (assessed as malondialdehyde production) was studied during in vitro alcohol metabolism by alcohol dehydrogenase. Peroxidation was initiated by acetaldehyde-xanthine oxidase, stimulated by ferritin, and inhibited by superoxide dismutase or chelation or iron with desferrioxamine. In conclusion, lipid peroxidation may be initiated during the metabolism of ethanol by alcohol dehydrogenase by an iron-dependent acetaldehyde-xanthine oxidase mechanism.
...
PMID:Acetaldehyde-mediated hepatic lipid peroxidation: role of superoxide and ferritin. 303 92

Lipid peroxidation has been invoked as a mechanism of alcoholic liver injury but its role has been controversial and the mechanism by which it occurs is unclear. Catalytic iron is known to play an important role in cellular injury and is produced during mobilization of ferritin iron. In vivo administration of a large acute dose of ethanol (5 g/kg) which produces hepatic lipid peroxidation in chow-fed rats resulted in mobilization of non-heme iron. The generation of NADH from alcohol metabolism via ADH or superoxide from acetaldehyde-xanthine oxidase mobilized iron from horse spleen ferritin in vitro. Chronic feeding of alcohol as 36% of energy for 6 weeks does not itself produce peroxidation in the rat but potentiates acute effects of ethanol. It produced microsomal induction which enhanced iron-stimulated lipid peroxidation and increased hepatic non-heme iron. Carbon monoxide increased rather than decreased accumulation of microsomal peroxidation products in vitro suggesting that cytochrome P-450 reductase mediates peroxidation but cytochrome P-450 may metabolize products. Incubation at lowered oxygen tensions equivalent to those observed in the perivenular zone (pO2 = 24 mmHg) enhanced in vitro iron mobilization but decreased peroxidation. Lipid peroxidation and its stimulation by iron mobilization and microsomal induction may be an important contributory mechanism of alcohol-induced liver injury.
...
PMID:Lipid peroxidation as a mechanism of alcoholic liver injury: role of iron mobilization and microsomal induction. 313 9

Administration of ethanol (5 g/kg p.o.) to female Sprague-Dawley rats resulted in conversion of a portion of hepatic xanthine dehydrogenase to xanthine oxidase 12 hr after treatment. Conversion was partly reversed in vitro by treatment of hepatic 100,000 X g supernatant with dithiothreitol, whereas pretreatment of rats with pyrazole (100 mg/kg i.p.) prevented conversion 18 hr after ethanol administration. Incubation of acetaldehyde with rat liver supernatant at 37 degrees C converted xanthine dehydrogenase to xanthine oxidase in a dose-dependent manner, whereas incubation of ethanol with rat liver supernatant did not lead to conversion. Acetaldehyde-induced conversion in vitro was reversed by treatment with dithiothreitol, and was partially blocked by addition of equimolar concentrations of reduced glutathione. These data suggest that biotransformation of ethanol is required for conversion of hepatic xanthine dehydrogenase to xanthine oxidase. Because xanthine oxidase utilizes molecular oxygen to produce superoxide radical, ethanol-induced conversion of xanthine dehydrogenase to xanthine oxidase could contribute to the enhanced lipid peroxidation reported previously after administration of a single dose of ethanol.
...
PMID:Effects of acute ethanol administration on the hepatic xanthine dehydrogenase/oxidase system in the rat. 316 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---