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)

Mammalian spermatozoa are sensitive to oxygen-induced damages mediated by lipid peroxidation of the cell membrane. The aim of this study was to evaluate whether reactive oxygen species (ROS) could also induce axonemal damage. When Percoll-separated spermatozoa were treated with hydrogen peroxide, or the combination xanthine and xanthine oxidase (X + XO), there was a progressive decrease, leading to a complete arrest, in sperm flagellar beat frequency. Once demembranated in a medium containing magnesium adenosine triphosphate (Mg.ATP), ROS-immobilized spermatozoa still reactivated motility; however, the percentage and duration of motility obtained in these tests gradually decreased to zero in the next hour. In 50% of the cases, motility of intact spermatozoa spontaneously reinitiated after 6 to 24 hours of immobilization due to ROS treatment, although with percentages and beat frequencies lower than those of untreated spermatozoa. Studies using ROS scavengers (such as catalase, superoxide dismutase, and dimethylsulfoxide) indicated that hydrogen peroxide was the most toxic of the ROS involved, but that .O2- and .OH probably also played a role in immobilization of spermatozoa by ROS. The data suggest that ROS induce a chain of events leading to sperm immobilization, that axonemes are affected, and that limited endogenous repair mechanisms exist to reverse these damages.
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PMID:Reactive oxygen species and human spermatozoa. I. Effects on the motility of intact spermatozoa and on sperm axonemes. 133 Oct 6

Peroxisomes are subcellular respiratory organelles which contain catalase and H2O2-producing flavin oxidases as basic enzymatic constituents. These organelles have an essentially oxidative type of metabolism and have the potential to carry out different important metabolic pathways. In recent years the presence of different types of superoxide dismutase (SOD) have been demonstrated in peroxisomes from several plant species, and more recently the occurrence of SOD has been extended to peroxisomes from human and transformed yeast cells. A copper,zinc-containing SOD from plant peroxisomes has been purified and partially characterized. The production of hydroxyl and superoxide radicals has been studied in peroxisomes. There are two sites of O2- production in peroxisomes: (1) in the matrix, the generating system being xanthine oxidase; and (2) in peroxisomal membranes, dependent on reduced nicotinamide adenine dinucleotide (NADH), and the electron transport components of the peroxisomal membrane are possibly responsible. The generation of oxygen radicals in peroxisomes could have important effects on cellular metabolism. Diverse cellular implications of oxyradical metabolism in peroxisomes are discussed in relation to phenomena such as cell injury, peroxisomal genetic diseases, peroxisome proliferation and oxidative stress, metal and salt stress, catabolism of nucleic acids, senescence, and plant pathogenic processes.
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PMID:Metabolism of oxygen radicals in peroxisomes and cellular implications. 133 30

A polarographic method to assess the scavenging capacity of a molecule for O2-. is proposed. This method is based on the fact that O2-. is not detected by the Clark electrode and that a scavenger competes with spontaneous dismutation of O2-. So, the reduction of O2 into O2-. and the decomposition of H2O2 by catalase, releasing O2, show a biphasic kinetic. Various kinetic parameters can be used to calculate the nmol of O2-. scavenged and also supply data on the reaction mechanisms (oxidation or reduction of O2-.) involved in scavenging. This method presents several other advantages: scavenging capacity can be assayed without added indicators which themselves behave as scavengers (as demonstrated for NBT), the presence of scavengers which interfere with the O2-. generating system (xanthine-xanthine oxidase) does not invalidate the measurements made.
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PMID:Superoxide anion scavenging capacity measured by a polarographic method. Comparison with a colourimetric method. 133 24

To help settle controversy as to whether the chelating agent diethylenetriaminepentaacetate (DTPA) supports or prevents hydroxyl radical production by superoxide/hydrogen peroxide systems, we have reinvestigated the question by spectroscopic, kinetic, and thermodynamic analyses. Potassium superoxide in DMSO was found to reduce Fe(III)DTPA. The rate constant for autoxidation of Fe(II)DTPA was found (by electron paramagnetic resonance spectroscopy) to be 3.10 M-1 s-1, which leads to a predicted rate constant for reduction of Fe(III)DTPA by superoxide of 5.9 x 10(3) M-1 s-1 in aqueous solution. This reduction is a necessary requirement for catalytic production of hydroxyl radicals via the Fenton reaction and is confirmed by spin-trapping experiments using DMPO. In the presence of Fe(III)DTPA, the xanthine/xanthine oxidase system generates hydroxyl radicals. The reaction is inhibited by both superoxide dismutase and catalase (indicating that both superoxide and hydrogen peroxide are required for generation of HO.). The generation of hydroxyl radicals (rather than oxidation side-products of DMPO and DMPO adducts) is attested to by the trapping of alpha-hydroxethyl radicals in the presence of 9% ethanol. Generation of HO. upon reaction of H2O2 with Fe(II)DTPA (the Fenton reaction) can be inhibited by catalase, but not superoxide dismutase. The data strongly indicate that iron-DTPA can catalyze the Haber-Weiss reaction.
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PMID:Catalysis of the Haber-Weiss reaction by iron-diethylenetriaminepentaacetate. 133 36

The ability of the superoxide radical (SOR) generated by xanthine oxidase to activate phospholipase A2 (PLA2) was examined in microsomes prepared from luteinized rat ovaries. Treatment of microsomes with xanthine oxidase resulted in a rapid burst in SOR formation followed by an increase in PLA2 activity. Stimulation of PLA2 activity was dose related and similar in microsomes prepared from control or prostaglandin F2 alpha (PGF2 alpha)-treated rats. Activation was inhibited by the antioxidants, vitamin E and nordihydroguaiaretic acid, and by superoxide dismutase and catalase, which metabolize SOR and H2O2 to remove reactive oxygen species from the cell. The stimulation of PLA2 activity by xanthine oxidase was dependent upon the addition of calcium ions, and it was highest in samples in which cytosol was added to membranes. These results indicate that the SOR and/or H2O2 may mediate PLA2 activation, which may be involved in the luteolytic process.
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PMID:Stimulation of phospholipase A2 by xanthine oxidase in the rat corpus luteum. 133 74

The reactions of native bovine catalase with superoxide and solvated electrons have been investigated using three different methods for generation of these reducing substrates: gamma-radiolysis of oxygenated or deaerated buffer solutions in the presence of an OH radical scavenger; either xanthine or acetaldehyde with xanthine oxidase; and low-temperature (77 K) gamma-radiolysis of buffered ethylene glycol/water solutions with subsequent annealing of samples at 183 K. The first spectral evidence for catalase compound II formation from native catalase via reaction with superoxide was obtained. The results are compared with results for peroxidase compound II or III formation observed under the same experimental conditions. A scheme is proposed to explain these observations involving intermediate formation of catalase compounds I and III and the ferrous enzyme. The one-electron reduction of catalase and peroxidase by radiolytically-generated solvated electrons was compared. In the present study the first absorption spectrum of a high-spin ferrous catalase which has peaks at 561 and 594 nm is reported, in comparison with a hemochromogen low-spin ferrous peroxidase observed under the same experimental conditions (peaks at 527 and 556 nm). Both spectra were recorded at 77 K. Data presented in this work also provide the first spectral evidence indicating the low temperature (183 K) conversion of high-spin ferrous catalase into compound III (oxycatalase) in the presence of dioxygen. Under the same experimental conditions low-spin ferrous peroxidase was converted into the high-spin ferrous form without oxyperoxidase formation.
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PMID:Spectral studies of intermediate species formed in one-electron reactions of bovine liver catalase at room and low temperatures. A comparison with peroxidase reactions. 136 11

Vascular smooth muscle cells (VSMCs) proliferate in response to arterial injury. Recent findings suggest that, in addition to platelet-derived growth factors, growth factors from inflammatory cells and endothelial cells at the site of injury may contribute to VSMC proliferation. We hypothesized that a common mechanism by which endothelial cells and inflammatory cells stimulate VSMC growth could be the active oxygen species (i.e., O2-, H2O2, and .OH) generated during arterial injury. Using xanthine/xanthine oxidase to generate active oxygen species, we studied the effects of these agents on VSMC growth. Xanthine/xanthine oxidase (100 microM xanthine and 5 microunits/ml xanthine oxidase) stimulated DNA synthesis in growth-arrested VSMCs by 180% over untreated cells. Administration of the scavenging enzymes superoxide dismutase and catalase demonstrated that H2O2 was primarily responsible for xanthine/xanthine oxidase-induced VSMC DNA synthesis. H2O2 directly increased VSMC DNA synthesis and cell number (maximal at 200 microM) but decreased DNA synthesis of endothelial cells and fibroblasts. This effect was protein kinase C independent: sphingosine, a potent protein kinase C inhibitor, failed to block H2O2-induced VSMC DNA synthesis. H2O2 (200 microM) stimulated c-myc and c-fos mRNA levels by fourfold and 20-fold, respectively, as compared with quiescent levels. In contrast to DNA synthesis, H2O2 induction of c-myc and c-fos mRNA was primarily protein kinase C dependent. These findings show that H2O2 specifically increases VSMC DNA synthesis and suggest a role for this oxidant in intimal proliferation, especially after arterial injury.
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PMID:Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. 2411 68

To explore the role of active oxygen species in the development and progression of acute pancreatitis, we studied the direct toxic effect on the rat pancreas of active oxygen species: superoxide anions generated by xanthine/xanthine oxidase (X/XO), and hydrogen peroxide (H2O2). After a continuous injection of X (10(-3)M, 0.9 ml/hour)/XO (1 U/ml, 0.3 ml/hour) into the celiac artery supplying the pancreas, hemorrhages and extensive edema developed in the pancreas. The amylase and lipase concentrations in the peritoneal fluid rose to 10.3 and 13.8 times the control values, respectively. The subsequent infusion of superoxide dismutase (SOD, 3600 U/hour) into the external jugular vein completely suppressed hemorrhages, and reduced edema and the amylase and lipase concentrations in the peritoneal fluid. After continuous injection of H2O2 (100 microM, 1.2 ml/hour), via the celiac artery, marked hemorrhages and edema appeared in the pancreas, and the amylase and lipase concentrations in the peritoneal fluid were 11.1 and 17.3 times higher than the control values, respectively. These abnormalities were significantly suppressed by the intravenous infusion of catalase (10 mg/kg/hour) or gabexate mesilate (10 mg/kg/hour). These results indicate that active oxygen species have a direct toxic effect on the pancreas and that free radicals may play an important role in the development of acute pancreatitis.
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PMID:Effect of intraarterial active oxygen species on the rat pancreas. 137 10

To clarify the role of oxygen radicals in the mucus metabolism of the gastrointestinal tract, the effect of oxygen radicals on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, was investigated using homogenate derived from rat gastric mucosa. The simultaneous addition of both xanthine and xanthine oxidase caused a significant inhibition of the enzyme activity, and this decrease was counteracted by catalase, but not by superoxide dismutase. Hydrogen peroxide also caused a significant decrease in the enzyme activity; and this effect of hydrogen peroxide was counteracted by catalase and dithiothreitol, but not by mannitol, dimethyl sulfoxide and reduced glutathione. The inhibition of glucosamine synthetase activity by oxygen radicals is considered to be caused by the oxidation of sulfhydryl groups of the enzyme molecule. The present results also suggest that oxygen radicals in the gastrointestinal tract may induce the suppression of a protective mechanism of the gastric mucosa by inhibiting glucosamine synthesis activity.
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PMID:Inhibition of gastric glucosamine synthetase activity by oxygen radicals: a possible cause of decreased mucosal protective capacity. 140 36

The effects of reactive oxygen species (ROS) on cultured rat mesangial cells were studied by measuring planar cell surface area (PCSA) after incubation with xanthine plus xanthine oxidase (XXO), in the presence of superoxide dismutase (SOD; 5 micrograms/ml) or catalase (CAT; 20 micrograms/ml), or after incubation with H2O2. Myosin light chain (MLC) phosphorylation was assessed in cells prelabeled with o-[32P]phosphoric acid and incubated with H2O2, after protein separation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible intermediate role for platelet-activating factor (PAF) was analyzed by preincubation of the cells with a PAF antagonist BN 52021 (BN, 5 x 10(-5) M) and by measuring PAF-specific [3H]acetate incorporation and immunoassayable PAF. XXO significantly decreased PCSA (14%), an effect abolished by CAT but not by SOD. H2O2 induced a similar effect, in a dose-dependent and time-dependent manner. MLC phosphorylation increased by 81 +/- 15% after H2O2 incubation, and this effect was blocked by BN. BN also completely blocked the effect of H2O2 on PCSA. PAF-specific [3H]acetate incorporation increased in the presence of H2O2 (from 6,886 +/- 2,030 to 58,703 +/- 16,063 counts.min-1.mg-1) as well as the immunoassayable PAF production by cells (from 0.90 +/- 0.19 to 6.71 +/- 2.27 ng/mg). These results suggest that ROS, particularly H2O2, could modulate the surface area of mesangial cells, modifying the ultrafiltration coefficient, thus explaining the decrease in glomerular filtration rate in those pathological situations characterized by an increased ROS synthesis. PAF could be involved in the genesis of these effects.
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PMID:Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat glomeruli. 141 75


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