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 purpose of this study was to explore the role of singlet oxygen in cardiovascular injury. To accomplish this objective, we investigated the effect of singlet oxygen [generated from photoactivation of rose-bengal] on the calcium transport and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum and compared these results with those obtained by superoxide radical, hydrogen peroxide and hydroxyl radical. Isolated cardiac SR exposed to rose bengal (10 nM) irradiated at (560 nm) produced a significant inhibition of Ca2+ uptake; from 2.27 +/- 0.05 to 0.62 +/- 0.05 mumol Ca2+/mg.min (mean +/- SE) (P less than 0.01) and Ca(2+)-ATPase activity from 2.08 +/- 0.05 mumol Pi/min.mg to 0.28 +/- 0.04 mumol Pi/min.mg (mean +/- SE) (P less than 0.01). The inhibition of calcium uptake and Ca(2+)-ATPase activity by rose bengal derived activated oxygen (singlet oxygen) was dependent on the duration of exposure and intensity of light. The singlet oxygen scavengers ascorbic acid and histidine significantly protected SR Ca(2+)-ATPase against rose bengal derived activated oxygen species but superoxide dismutase and catalase did not attenuate the inhibition. SDS-polyacrylamide gel electrophoresis of SR exposed to photoactivated rose bengal up to 14 min, demonstrated complete loss of Ca(2+)-ATPase monomer band which was significantly protected by histidine. Irradiation of rose bengal also caused an 18% loss of total sulfhydryl groups of SR. On the other hand, superoxide (generated from xanthine oxidase action on xanthine) and hydroxyl radical (0.5 mM H2O2 + Fe(2+)-EDTA) as well as H2O2 (12 mM) were without any effect on the 97,000 dalton Ca(2+)-ATPase band of sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Singlet oxygen: a potential culprit in myocardial injury? 131 3

Oxygen free radicals have been demonstrated to be important mediators in postischemic reperfusion injury. In this study, I determined the superoxide and the hydrogen peroxide generation from human umbilical endothelial cells on reoxygenation following anoxic incubation (1% O2, 5% CO2, 94% N2). The superoxide generation, detected by the reduction of cytochrome, c, was at its maximum 3 minutes after reoxygenation in any anoxic interval. The hydrogen peroxide production, detected by the fluorometric analysis, was observed later than that of superoxide. Treatment of EC with superoxide dismutase and allopurinol attenuated the superoxide production, and catalase attenuated the hydrogen peroxide. Cell injury was assessed by both fura-2 release assay and trypan blue dye exclusion methods. Although cell injury was less than 20% in anoxic condition, it was remarkably increased after reoxygenation. However this cell injury was not completely prevented in the presence of free radical scavengers. Allopurinol was more effective than superoxide dismutase or catalase. In conclusion, EC are the major source of free radicals in postischemic reperfusion which are originated mainly from xanthine-xanthine oxidase system and these radicals may also contribute, at least in part, to the EC injury.
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PMID:[Measurement of free radical generation from endothelial cells and observation of cell injury exposed to anoxia-reoxygenation]. 131 95

The effects of xanthine + xanthine oxidase-generated reactive oxygen species (ROS) on rabbit muscle creatine kinase (CK) were studied. Xanthine (0.1 mM) + xanthine oxidase (30 mU/ml) inhibited activity of rabbit muscle CK (1.2 mU/ml). Catalase (100 U/ml), but not SOD (100 Uml), deferoxamine (100 microM) or mannitol (20 mM), protected CK from inactivation; suggesting that H2O2 was responsible for inactivation. These results were different from previously reported findings on bovine heart CK that superoxide radicals inactivate the enzyme. Thus, enzymes with homologous structures may have different reactivities to different ROS. H2O2-induced inactivation of rabbit muscle CK was accompanied by a decrease in its thiol group content, whereas no significant changes in the protein structure were detected by SDS-PAGE or carbonyl content. These results suggest that oxidation of -SH groups by H2O2 seems to be a major mechanism of activation of rabbit muscle CK by xanthine + xanthine oxidase. Such inactivation of CK by H2O2 may be important in ROS-induced pathology.
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PMID:Inactivation of rabbit muscle creatine kinase by hydrogen peroxide. 132 Oct 75

Picroliv, the active principle of Picrorhiza kurrooa, and its main components which are a mixture of the iridoid glycosides, picroside-I and kutkoside, were studied in vitro as potential scavengers of oxygen free radicals. The superoxide (O2-) anions generated in a xanthine-xanthine oxidase system, as measured in terms of uric acid formed and the reduction of nitroblue tetrazolium were shown to be suppressed by picroliv, picroside-I and kutkoside. Picroliv as well as both glycosides inhibited the non-enzymic generation of O2- anions in a phenazine methosulphate NADH system. Malonaldehyde (MDA) generation in rat liver microsomes as stimulated by both the ascorbate-Fe2+ and NADPH-ADP-Fe2+ systems was shown to be inhibited by the Picroliv glycosides. Known antioxidants tocopherol (vitamin E) and butylated hydroxyanisole (BHA) were also compared with regard to their antioxidant actions in the above system. It was found that BHA afforded protection against ascorbate-Fe(2+)-induced MDA formation in microsomes but did not interfere with enzymic or non-enzymic O2- anion generation; and tocopherol inhibited lipid peroxidation in microsomes by both prooxidant systems and the generation of O2- anions in the non-enzymic system but did not interfere with xanthine oxidase activity. The present study shows that picroliv, picroside-I and kutkoside possess the properties of antioxidants which appear to be mediated through activity like that of superoxide dismutase, metal ion chelators and xanthine oxidase inhibitors.
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PMID:Picroliv, picroside-I and kutkoside from Picrorhiza kurrooa are scavengers of superoxide anions. 132 26

We examined the protective effect of cellular superoxide dismutase against extracellular hydrogen peroxide in cultured bovine aortic endothelial cells. 51Cr-labeled cells were exposed to hydrogen peroxide generated by glucose oxidase/glucose. Glucose oxidase caused a dose-dependent increase of 51Cr release. Pretreatment with diethyldithiocarbamate enhanced injury induced by glucose oxidase, corresponding with the degree of inhibition of endogenous superoxide dismutase activity. Inhibition of cellular superoxide dismutase by diethyldithiocarbamate was not associated either with alteration of other antioxidant defenses or with potentiation of nonoxidant injury. Enhanced glucose oxidase damage by diethyldithiocarbamate was prevented by chelating cellular iron. Inhibition of cellular xanthine oxidase neither prevented lysis by hydrogen peroxide nor diminished enhanced susceptibility by diethyldithiocarbamate. These results suggest that, in cultured endothelial cells: 1) cellular superoxide is involved in mediating hydrogen peroxide-induced damage; 2) superoxide, which would be generated upon exposure to excess hydrogen peroxide independently of cellular xanthine oxidase, promotes the Haber-Weiss reaction by initiating reduction of stored iron (Fe3+) to Fe2+; 3) cellular iron catalyzes the production of a more toxic species from these two oxygen metabolites; 4) cellular superoxide dismutase plays a critical role in preventing hydrogen peroxide damage by scavenging superoxide and consequently by inhibiting the generation of the toxic species.
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PMID:Role of cellular superoxide dismutase against reactive oxygen metabolite injury in cultured bovine aortic endothelial cells. 132 16

Since 3-hydroxyanthranilic acid (3HAA), an oxidation product of tryptophan metabolism, is a powerful radical scavenger [Christen, S., Peterhans, E., & Stocker, R. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2506], its reaction with peroxyl radicals was investigated further. Exposure to aqueous peroxyl radicals generated at constant rate under air from the thermolabile radical initiator 2,2'-azobis[2-amid-inopropane] hydrochloride (AAPH) resulted in rapid consumption of 3HAA with initial accumulation of its cyclic dimer, cinnabarinic acid (CA). The initial rate of formation of the phenoxazinone CA accounted for approximately 75% of the initial rate of oxidation of 3HAA, taking into account that 2 mol of 3HAA are required to form 1 mol of CA. Consumption of 3HAA under anaerobic conditions (where alkyl radicals are produced from AAPH) was considerably slower and did not result in detectable formation of CA. Addition of superoxide dismutase enhanced autoxidation of 3HAA as well as the initial rates of peroxyl radical-induced oxidation of 3HAA and formation of CA by approximately 40-50%, whereas inclusion of xanthine/xanthine oxidase decreased the rate of oxidation of 3HAA by approximately 50% and inhibited formation of CA almost completely, suggesting that superoxide anion radical (O2.-) was formed and reacted with reaction intermediate(s) to curtail formation of CA. Formation of CA was also observed when 3HAA was added to performed compound I of horseradish peroxidase (HRPO) or catalytic amounts of either HRPO, myeloperoxidase, or bovine liver catalase together with glucose/glucose oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidation of 3-hydroxyanthranilic acid to the phenoxazinone cinnabarinic acid by peroxyl radicals and by compound I of peroxidases or catalase. 132 27

Ischemia-reperfusion is observed in various diseases such as myocardium infarct. Different theories have been proposed to explain the reperfusion injury, among them that the free radical generation plays a crucial role. To study the mechanisms of the reperfusion injury, a hypoxia (H)-reoxygenation (R) model upon human umbilical vein endothelial cells in culture was developed in order to mimic the in vivo situation. Different parameters were quantified and compared under H or H/R, and we found that oxygen readmission led to damage amplification after a short hypoxia period. To estimate the importance of various causes of toxicity, the effects of various protective molecules were compared. Different antioxidant molecules, iron-chelating agent, xanthine oxidase inhibitors, and energy-supplying molecules were very efficient protectors. Synergy could also be observed between the antioxidants and the energy-supplying molecules or the xanthine oxidase inhibitors. The toxic effect of O2.(-) could be lowered by the presence of SOD or glutathione peroxidase in the culture medium, whereas glutathione peroxidase was the most efficient enzyme when injected into the cells. The production of O2.(-) and of H2O2 by endothelial cells was directly estimated to be, respectively, of 0.17 and 0.035 mumol/min/mg prot during the R period. O2.(-) production was completely inhibited when allopurinol was added during H and R. In addition, a xanthine oxidase activity of 21.5 10(-6) U/mg prot could be observed by a direct assay in cells after H but not in control cells, thus confirming the previous conclusions of xanthine oxidase as a potent source of free radicals in these conditions. Thanks to the use of cultured human endothelial cells, a clear picture was obtained of the overall process leading to cell degenerescence during the reoxygenation process. We particularly could stress the importance of the low energetic state of these cells, which is a critical factor acting synergistically with the oxidant molecules to injure the cells. These results also open new possibilities for the development of new therapeutics for ischemia.
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PMID:Human umbilical vein endothelial cells submitted to hypoxia-reoxygenation in vitro: implication of free radicals, xanthine oxidase, and energy deficiency. 132 79

Active oxygen species cause gastric mucosal damage in vivo. However, it is not known if these species are directly cytotoxic toward gastric cells. Prostaglandins have important physiological roles in the gastric mucosa, including direct cell protection against damaging factors. So, to find if active oxygen species affect prostaglandin synthesis in gastric mucosal cells is important, but this also is not known. This study was done to investigate the effects of such species on damage to and prostaglandin synthesis in cultured mucus-producing cells from rat gastric mucosa. Active oxygen species were produced by the addition of xanthine and xanthine oxidase to the culture medium. Cytotoxicity was assayed by 51Cr release. Xanthine (1 mM) and xanthine oxidase (100 mU/ml) increased specific 51Cr release as the thiobarbituric acid reactants increased. This increase in 51Cr release was inhibited by catalase, a scavenger of hydrogen peroxide, or dimethyl sulfoxide, a scavenger of hydroxyl radicals, but not by superoxide dismutase, a scavenger of superoxide, nor deferoxamine, an inhibitor of hydroxyl radical generation. Catalase, dimethyl sulfoxide, and superoxide dismutase each had no effect on prostaglandin E2 synthesis when xanthine and xanthine oxidase were not added. In the presence of xanthine and xanthine oxidase, catalase and dimethyl sulfoxide stimulated the synthesis of prostaglandin E2 and superoxide dismutase inhibited it. Indomethacin, a prostaglandin synthetase inhibitor, did not affect the decrease in 51Cr release caused by catalase in the presence of xanthine and xanthine oxidase, but it abolished the decrease caused by dimethyl sulfoxide. These results suggest that hydrogen peroxide, but not superoxide nor hydroxyl radicals, is involved in damage to cultured rat gastric cells, and that superoxide stimulates prostaglandin E2 synthesis, but that hydrogen peroxide inhibits it. Protection of the cells by dimethyl sulfoxide may be related to stimulation of prostaglandin E2 synthesis in the cells, but not via scavenging hydroxyl radicals.
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PMID:Effects of active oxygen species on damage to and prostaglandin synthesis in cultured rat gastric cells. 132 36

The mechanism of modulation of cyclic guanosine monophosphate (cGMP) accumulation by methylene blue (MB), a putative inhibitor of soluble guanylate cyclase, was investigated in cultured rabbit pulmonary arterial smooth muscle cells (RPASM). Control or MB-pretreated RPASM were stimulated with sodium nitroprusside (SNP), nitrosothiols or endothelium-derived relaxing factor (EDRF) released basally from bovine pulmonary arterial endothelial cells, in short-term co-cultures. The putative EDRF, S-nitroso-L-cysteine (CYSNO), a stable deaminated analog of CYSNO, S-nitroso-3-mercaptoproprionic acid (MPANO) and SNP produced concentration-dependent (1-100 microM) increase (1.5- to 12-fold) in RPASM cGMP levels. MB pretreatment inhibited CYSNO and SNP-induced cGMP accumulation by 51% to 100%, but MPANO-mediated responses were not altered by MB. The inhibition profile of MB on nitrovasodilator-induced cGMP accumulation was quantitatively reproduced by extracellular generation of superoxide anion with xanthine (100 microM) and xanthine oxidase (5 mU). Similarly to MB pretreatment, superoxide anion generation had no effects on base-line cGMP levels or cGMP responses elicited by MPANO. Furthermore, MB induced a dose- and time-dependent generation of superoxide anion from RPASM, as evidenced from spectrophotometric determination of cytochrome c reduction. Inhibition of cGMP accumulation in response to CYSNO and SNP by MB was completely prevented by superoxide dismutase but not catalase. Selective pretreatment of endothelial cells with MB before co-culture with untreated RPASM produced a reduction in RPASM cGMP levels of a magnitude comparable with that seen in co-cultures of MB-pretreated RPASM with untreated endothelial cells, and which was partially prevented by superoxide dismutase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Methylene blue inhibits nitrovasodilator- and endothelium-derived relaxing factor-induced cyclic GMP accumulation in cultured pulmonary arterial smooth muscle cells via generation of superoxide anion. 132 4

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


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