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)

The sensitivity of Candida albicans cells to killing by hydrogen peroxide was found to increase markedly when they were grown in the presence of sub-growth-inhibitory concentrations of the azole drug clotrimazole (CTZ). A superoxide anion-generating system consisting of xanthine and xanthine oxidase also killed such CTZ-treated cells more efficiently than control cells, but this seemed to be accounted for by hydrogen peroxide secondarily formed from superoxide anion as judged by the effect of catalase and superoxide dismutase. The increased sensitivity to hydrogen peroxide was considered to be attributable to the inhibition of 14 alpha-demethylation of ergosterol biosynthesis by CTZ, since a 14 alpha-demethylation-deficient mutant of C. albicans exhibited a similar phenotype. It is suggested that the in vivo efficacy of azole antifungal agents against C. albicans infection is at least partially due to the sensitization of the fungal cells to the oxygen-dependent microbicidal system of the phagocyte.
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PMID:Increased sensitivity of Candida albicans cells accumulating 14 alpha-methylated sterols to active oxygen: possible relevance to in vivo efficacies of azole antifungal agents. 132 23

This study was undertaken to examine the effects of oxygen free radicals on mitochondrial creatine kinase activity in rat heart. Xanthine plus xanthine oxidase (superoxide anion radical generating system) reduced mitochondrial creatine kinase activity both in a dose- and a time-dependent manner. Superoxide dismutase showed a protective effect on depression in creatine kinase activity due to xanthine plus xanthine oxidase. Hydrogen peroxide inhibited creatine kinase activity in a dose-dependent manner, this inhibition was protected by the addition of catalase. In order to understand the detailed mechanisms by which oxygen free radicals inhibit mitochondrial creatine kinase activity, the effects of oxygen free radicals on mitochondrial sulfhydryl groups were examined. Mitochondrial sulfhydryl groups contents were decreased by xanthine plus xanthine oxidase or hydrogen peroxide; this depression in sulfhydryl groups contents was prevented by the addition of superoxide dismutase or catalase. N-Ethylmaleimide (sulfhydryl group reagent) expressed inhibitory effects on the creatine kinase activity both in a dose- and a time-dependent manner; dithiothreitol or cysteine (sulfhydryl group reductant) showed protective effects on the creatine kinase activity depression induced by N-ethylmaleimide. Dithiothreitol or cysteine also blocked the depression of mitochondrial creatine kinase activity caused by xanthine plus xanthine oxidase or hydrogen peroxide. These results lead us to conclude that oxygen free radicals may inhibit mitochondrial creatine kinase activity by modifying sulfhydryl groups in the enzyme protein.
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PMID:Decrease in heart mitochondrial creatine kinase activity due to oxygen free radicals. 132 80

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

To evaluate the regulation of endothelial cell Cu,Zn-SOD, we have exposed bovine pulmonary artery endothelial cells in culture to hyperoxia and hypoxia, second messengers or related agonists, hormones, free radical generating systems, endotoxin, and cytokines and have measured Cu,Zn-SOD protein of these cells by an ELISA developed in our laboratory. Control preconfluent and confluent cells in room air contained 196 +/- 18 ng Cu,Zn-SOD/10(6) cells. A23187 (0.33 microM), forskolin (10 microM), isobutylmethylxanthine (0.1 mM), dexamethasone (1 microM), triiodothyronine (1 microM) and retinoic acid (1 microM) failed to alter this level of Cu,Zn-SOD. Exposure to anoxia and hyperoxia both elevated the level approximately 1.5-2.0-fold over 20% oxygen-exposed controls at 48-72 hr. Similarly, exposures to glucose oxidase (0.0075 units/ml), menadione (12.5 microM), xanthine-xanthine oxidase (10 microM, 0.03 units/ml) and H2O2 (0.0005%) increased the level up to two-threefold over controls at 24-48 hr. Lipopolysaccharide, TGF beta 1, TNF alpha, and Il-1 also increased levels of cellular Cu,Zn-SOD, but only in proliferating cells. Il-2, Il-4, interferon-gamma, and GM-CSF had no effect on Cu,Zn-SOD. All treatments that elevated SOD resulted in inhibition of cellular growth, but decreased growth of cells at confluence alone was not associated with increased Cu,Zn-SOD. We propose from these studies that Cu,Zn-SOD of endothelial cells is not under conventional second messenger or hormonal regulation, but that up-regulation of the enzyme is associated with (and perhaps stimulated by) free-radical or oxidant production that also may be influenced by availability of certain cytokines under replicating conditions.
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PMID:Regulation of Cu,Zn-superoxide dismutase in bovine pulmonary artery endothelial cells. 133 80

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

The formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthesized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase in the presence of BABQ derivatives. At low concentrations (< 10 microM) some BABQ derivatives turned out to inhibit the production of superoxide and hydroxyl radicals by xanthine oxidase, while the effect on the xanthine-oxidase-induced production of hydrogen peroxide was much less pronounced. Induction of DNA strand breaks by reactive oxygen species generated by xanthine oxidase was also inhibited by BABQ derivatives. The DNA damage was comparable to the amount of hydroxyl radicals produced. The inhibiting effect on hydroxyl radical production can be explained as a consequence of the lowered level of superoxide, which disrupts the Haber-Weiss reaction sequence. The inhibitory effect of BABQ derivatives on superoxide formation correlated with their one-electron reduction potentials: BABQ derivatives with a high reduction potential scavenge superoxide anion radicals produced by xanthine oxidase, leading to reduced BABQ species and production of hydrogen peroxide from reoxidation of reduced BABQ. This study, using a unique series of BABQ derivatives with an extended range of reduction potentials, demonstrates that the formation of superoxide and hydroxyl radicals by bioreductively activated antitumor quinones can in principle be uncoupled from alkylating activity.
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PMID:Redox cycling of potential antitumor aziridinyl quinones. 133 33

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

Reactive oxygen metabolites are implicated in tissue damage, which is often followed by fibrosis. Our aim was to evaluate the sensitivity of human fibroblasts, in comparison with umbilical vein endothelial cells, to two common reactive oxygen metabolites, to superoxide produced by hypoxanthine and xanthine oxidase, and to reagent hydrogen peroxide. Depletion of the prelabeled adenine nucleotide pool, which is a sensitive index of cell damage, was used as the basis for comparison. In the presence of hypoxanthine, xanthine oxidase caused a dose-dependent nucleotide depletion, which was more pronounced in endothelial cells. After 4 h of exposure to 100 microM hypoxanthine and 80 mU/mL xanthine oxidase, fibroblasts retained 73 +/- 2% of their adenine nucleotides but endothelial cells retained only 11 +/- 2%. Hydrogen peroxide also had a larger effect on endothelial cells; after exposure to 100 microM for 30 min, adenine nucleotides retained 36 +/- 26% of their initial radioactivity in endothelial cells but 76 +/- 8% in fibroblasts. We conclude that umbilical vein endothelial cells are inherently more sensitive to the harmful effects of reactive oxygen metabolites than are fetal skin fibroblasts.
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PMID:Differential sensitivity of human fibroblasts and endothelial cells to reactive oxygen metabolites. 133 84

Iodination stimulators, such as the dehydrogenation polymer of caffeic acid (DHP-CA), a protein-bound polysaccharide (PSK), and a commercially available tannic acid, potently inhibited the luciferin-dependent chemiluminescence (LDCL) generated by opsonized zymosan-stimulated human peripheral blood polymorphonuclear cells (PMN). Continuous presence of these substances was necessary to express their inhibitory activity. The extent of inhibition paralleled their ability to scavenge the chemiluminescence generated by the xanthine-xanthine oxidase reaction. They also scavenged the chemiluminescence generated by potassium superoxide solution, but less effectively. An electron paramagnetic resonance spin-trapping technique revealed that DHP-CA significantly, but incompletely, scavenged O2-. The results suggest that O2- might be scavenged both directly by iodination stimulators, and by other oxygen radicals produced by activation of myeloperoxidase-mediated reaction.
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PMID:O2- scavenging activity of lignins, tannins and PSK. 133 73

On the basis of a recent report that minocycline is effective in the treatment of acne inflammation by acting directly as an antioxidant on infiltrating neutrophils, we investigated whether doxycycline might also be capable of reducing the generation of reactive oxygen species, using human neutrophils and a cell-free, xanthine-xanthine oxidase system. The species investigated are superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). Doxycycline significantly reduced the levels of O2-, H2O2 and OH. generated by both systems. Our results seem to suggest that the clinical effectiveness of doxycycline in the treatment of acne inflammation is due partly to its antioxidant effect on neutrophils.
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PMID:Effect of doxycycline on the generation of reactive oxygen species: a possible mechanism of action of acne therapy with doxycycline. 135 52


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