Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the reductive process in the tissues, the aerobes generate a number of oxidants. Unless these oxidants are reduced, oxidative damage and cell death would occur. Oxidation of plasma membrane lipids leads to autocatalytic chain reactions which eventually alter the permeability of the cell. The role of oxidative damage in the pathophysiology of diabetic complications and ischemic reperfusion injury of myocardium, especially the changes in the channel activity which may lead to arrhythmia have been studied. Hyperglycemia activates aldose reductase which could efficiently reduce glucose to sorbitol in the presence of NADPH. Since NADPH is also aldose required by glutathione reductase for reducing oxidants, its diversion would lead to membrane lipid oxidation and permeability changes which are probably responsible for diabetic complications such as cataractogenesis, retinopathy, neuropathy etc. Antioxidants such as butylated hydroxy toluene (BHT) and also reductase inhibitors prevent or delay some of these complications. By using patch-clamp technique in isolated frog myocytes, we have shown that hydroxy radicals generated by ferrous sulfate and ascorbate as well as lipid peroxides such as t-butyl hydroperoxide facilitate the entry of Na+ by oxidizing Na+-channels. Increased intracellular Na+ leads to an increase in Na+/Ca2+ exchange. The increased Na+ concentration by itself may produce electrical disturbance which would result in arrhythmia. Increased Ca2+ may affect proteases and may help in the conversion of xanthine dehydrogenase to xanthine oxidase, consequently increased production of super oxide radicals. Increased membrane lipid peroxidation and other oxygen free-radical associated membrane damage in myocytes has been demonstrated.
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PMID:The effect of oxidants on biomembranes and cellular metabolism. 251 41

The generation of free oxygen radicals from the xanthine-xanthine oxidase system produced a decrease in the steady-state calcium load of canine cardiac sarcoplasmic reticulum (SR) vesicles and an increase in the SR passive calcium permeability. This effect of free oxygen radicals was completely inhibited by superoxide dismutase, a scavenger of superoxide anion radical (.O2-). Treatment of intact SR with a specific calmodulin antagonist, compound 48/80 or W-7, lead to the enhancement of the free oxygen radical-mediated reduction of steady-state calcium accumulation with little effect on passive calcium permeability and Ca,Mg-adenosine triphosphatase activity. The effects of free oxygen radicals and the calmodulin antagonists on steady-state calcium accumulation, but not on passive calcium permeability, were only observed in the presence of the endogenous calmodulin of SR vesicles. These results indicate that stimulation by .O2- and/or a closely related species of free oxygen radical of the passive calcium leak pathway is not calmodulin-dependent and is not a potent way of changing the steady-state calcium accumulation. Hence, we propose that calmodulin-dependent component of calcium fluxes in cardiac SR vesicles is modified directly by free oxygen radicals, and that free oxygen radicals can reduce steady-state calcium accumulation due to increased calcium release through a calcium efflux pathway which is inhibited by calmodulin, but not due to reduced catalytic activity of the pump.
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PMID:Calmodulin and free oxygen radicals interaction with steady-state calcium accumulation and passive calcium permeability of cardiac sarcoplasmic reticulum. 252 16

Although oxygen free radicals have been implicated as mediators of cellular injury in myocardial ischemia-reperfusion, the exact nature of defects produced by these radicals is not clear. Because sarcolemmal Ca2+-pump is involved in the efflux of Ca2+ from the cell, this study was undertaken to examine the effects of oxygen free radicals on sarcolemmal ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent adenosinetriphosphatase (ATPase) activities as well as lipid peroxidation of membrane phospholipids. Isolated rat heart sarcolemmal membranes were incubated with xanthine + xanthine oxidase [a superoxide anion radical (O2-)-generating system], H2O2, or H2O2 + Fe2+ [a hydroxyl radical (HO.)-generating system] and assayed for Ca2+-pump activities. O2- inhibited the Ca2+-pump activities in a time-dependent manner; a significant inhibition of Ca2+-stimulated ATPase activity was seen after 1 min of incubation. Superoxide dismutase showed a protective effect on depression in Ca2+-pump activities caused by O2-.H2O2 inhibited Ca2+-pump activities in a dose-dependent manner; this inhibition was protected by the addition of catalase. HO. depressed the Ca2+-pump activities to a greater extent in comparison with H2O2. Mannitol showed a protective effect on HO.-induced inhibition of Ca2+-pump activities. The promotion of lipid peroxidation by free radicals was evident from increased formation of malondialdehyde. These results indicate that the sarcolemmal membrane is altered on exposure to oxygen free radicals, and this may result in depressing the Ca2+-pump mechanism for Ca2+ efflux from the myocardial cell.
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PMID:Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals. 253 32

Superoxide radicals inactivate endoplasmic reticular (ER) Ca2+ pump in membranes isolated from smooth muscle of pig right coronary artery [Am. J. Physiol. 255 (Cell Physiol. 24): C297-C303, 1988]. We report on protective mechanisms against such inactivation. This tissue contained superoxide dismutase (SOD) and catalase. SOD was distributed primarily in cytosolic fraction, was cyanide sensitive, and was also present in mitochondrial fraction, and approximately 25% of this was cyanide insensitive. Catalase was distributed mainly in mitochondrial fraction and did not protect against inactivation of ER Ca2+ pump by superoxide radicals generated using xanthine plus xanthine oxidase. However, cytosolic fraction protected against this inactivation by two mechanisms: 1) DTT carried over from homogenization medium and 2) its intrinsic SOD content. Soluble fraction was concentrated, dialyzed to remove 1,4-dithiothreitol (DTT), lyophilized, and suspended in a small volume of DTT-free buffer. It still protected against superoxide inactivation of Ca2+ pump. On Sephacryl-300 gel chromatography, protecting activity comigrated with SOD. DTT protected against inactivation, but glutathione and cysteine protected only partially. Neither sulfhydryl agents nor SOD could reverse the inactivation process. Ca2+ pump activity was abolished by dithionitrobenzoate and p-chloromercuric benzoate. Superoxide may inactivate ER Ca2+ pump by irreversibly modifying key sulfhydryl group(s) on pump molecule and SOD in coronary artery smooth muscle may partially protect against this inactivation.
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PMID:Protection of Ca pump of coronary artery against inactivation by superoxide radical. 253 68

Prior studies, both in vitro and in vivo, have suggested that cutaneous porphyrin photosensitization requires the generation of superoxide anion (.O2-) and various other reactive oxygen metabolites. No unifying concept has emerged, however, that unequivocally demonstrates the source of generation of these species. Since xanthine oxidase is known to generate .O2- in reperfused ischemic tissue and in certain inflammatory disorders, we attempted to assess its role in porphyrin photosensitization. C3H mice were rendered photosensitive by the intraperitoneal administration of dihematoporphyrin ether (DHE) (5 mg/kg) followed by irradiation with visible light. Murine ear swelling was used as a marker of the acute photosensitization response and involvement of oxygen radicals was evaluated using electron spin resonance (ESR) spectroscopy. The administration of allopurinol, a potent inhibitor of xanthine oxidase, afforded 90% protection against DHE-mediated acute photosensitivity in vivo. Furthermore, xanthine oxidase activity was twofold higher in the skin of photosensitized mice than in unirradiated animals. ESR spectra of 5,5-dimethyl-1-pyrroline N-oxide-trapped radicals from the skin of photosensitized mice verified the presence of .O2- and .OH, while neither of these species was detected in the skin of control mice or mice receiving allopurinol. The administration of a soybean trypsin inhibitor or verapamil before irradiation also partially blocked the photosensitivity response, suggesting that calcium-dependent proteases play a role in the activation of xanthine oxidase in this photodynamic process. These data provide in vivo evidence for the involvement of .O2- in DHE-mediated cutaneous photosensitization and suggest that these radicals are generated through the activation of the xanthine oxidase pathway. The administration of allopurinol and calcium channel blockers may thus offer new approaches for the treatment of cutaneous porphyrin photosensitization.
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PMID:A novel mechanism for the generation of superoxide anions in hematoporphyrin derivative-mediated cutaneous photosensitization. Activation of the xanthine oxidase pathway. 253 90

The calcium ionophore A23187 causes endothelium-dependent contractions in canine basilar arteries. Removal of the endothelium, or treatment with indomethacin or superoxide dismutase (SOD), prevented the endothelium-dependent excitatory effect of the calcium ionophore. Catalase and deferoxamine were without effect. Superoxide anion generated by xanthine plus xanthine oxidase in the presence of catalase caused contractions of the vascular smooth muscle, which were abolished by SOD or heat inactivation of xanthine oxidase. The A23187-induced production of prostaglandins F2 alpha and E2 and thromboxane B2 was abolished by the removal of endothelium and by treatment with indomethacin but was not affected by the presence of SOD plus catalase. These observations are consistent with the hypothesis that superoxide anion, rather than prostaglandins generated by hydroperoxidase activity of cyclooxygenase, is an endothelium-derived contracting factor in canine cerebral arteries.
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PMID:Superoxide anion is an endothelium-derived contracting factor. 254 50

As guinea-pig pulmonary macrophages (PM) synthesize the linoleic acid metabolite 9-hydroxy-octadecadienoic acid (9-OH-Lin) under non-stimulated conditions in relatively large quantities, we investigated whether this product has an effect on the macrophage's own phagocytic cell function. 9-OH-Lin, and also its hydroperoxy precursor 9-hydroperoxy-octadecadienoic acid (9-OOH-Lin), influenced the generation of PM chemiluminescence, a measure of the production of reactive oxygen species. The generation of lucigenin-enhanced chemiluminescence by stimulated and non-stimulated PM was inhibited concentration-dependently. Inhibition was observed at concentrations as low as 10 nM. Since 9-OH-Lin and 9-OOH-Lin also inhibited the generation of chemiluminescence by a cell-free enzyme system, i.e. xanthine/xanthine oxidase, the inhibitory effects might represent a scavenging activity towards reactive oxygen species. 9-OH-Lin and 9-OOH-Lin did not influence other phagocytic cell functions, e.g. PM phagocytic capacity, the aggregatory response to the calcium ionophore A23187, or the release of lysosomal enzymes. The effects of 9-OH-Lin and 9-OOH-Lin could be ascribed to the hydroxy and hydroxyperoxy moiety, respectively, as evidenced by lack of effect of the native fatty acid linoleic acid. We conclude that the formation of 9-OH-Lin and 9-OOH-Lin by PM may represent a regulatory mechanism towards the cell's own activity by modulating reactive oxygen species.
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PMID:Modulatory activity of 9-hydroxy- and 9-hydroperoxy-octadecadienoic acid towards reactive oxygen species from guinea-pig pulmonary macrophages. 255 Feb 27

To understand the involvement of changes in sulfhydryl groups in causing depression of the sarcolemmal Ca2+-pump activities, this study was undertaken to examine the effects of oxygen free radicals on rat heart sarcolemmal sulfhydryl groups, Ca2+-stimulated adenosinetriphosphatase (ATPase), and ATP-dependent Ca2+ accumulation. In addition, the effects of sulfhydryl reagents such as dithiothreitol, cysteine, and N-ethylmaleimide on Ca2+-pump activities were investigated. The inhibition of sarcolemmal Ca2+-pump activities by O2-. (xanthine + xanthine oxidase) and H2O2 was decreased by the addition of dithiothreitol or cysteine in a dose-dependent manner. N-ethylmaleimide also showed inhibitory effects on Ca2+-pump activities both in a dose- and time-dependent manner; dithiothreitol and cysteine prevented changes in Ca2+-pump activities because of N-ethylmaleimide. Heart sarcolemmal sulfhydryl groups were depressed by O2-., H2O2, and .OH (H2O2 + Fe2+) both in a dose- and time-dependent manner. Superoxide dismutase, catalase, and D-mannitol showed protective effects on the sulfhydryl group depression by O2-., H2O2, and .OH, respectively. A significant correlation between changes in sarcolemmal Ca2+-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen. These results indicate that oxygen free radicals may depress the heart sarcolemmal Ca2+-pump activities by modifying the sulfhydryl groups in the sarcolemmal membrane.
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PMID:Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals. 255 Nov 90

In view of the importance of Ca2+-channels in controlling the entry of Ca2+ into the myocardium, this study was undertaken to examine the effects of oxygen free radicals on the binding of Ca2+-channel antagonists in rat heart by employing [3H]-nitrendipine as a ligand. Isolated heart membranes were incubated with xanthine + xanthine oxidase (a superoxide anion radicals generating system), hydrogen peroxide (an activated species of oxygen), or hydrogen peroxide + Fe2+ (a hydroxyl radicals generating system). The assay of the [3H]-nitrendipine binding activity revealed that the maximal number of binding sites (Bmax) were reduced in a time-dependent manner by superoxide radicals without any changes in the binding constant (Kd); a significant reduction of Bmax was seen after incubating membranes with xanthine + xanthine oxidase for a 10-min-period. Superoxide dismutase showed a protective effect on the superoxide radicals induced reduction in Bmax. Both hydrogen peroxide and hydroxyl radicals also depressed the Bmax for [3H]-nitrendipine binding without any significant change in Kd; catalase and mannitol showed protective effects on hydrogen peroxide or hydroxyl radicals induced depression in Bmax, respectively. These results indicate that oxygen free radicals may reduce the number of Ca2+-channels in the cell membrane and this change may contribute towards decreasing the voltage-dependent Ca2+ influx in the cardiac cell.
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PMID:Reduction of calcium channel antagonist binding sites by oxygen free radicals in rat heart. 255 87

Experimental Mg2+ deficiency was induced in a group of rats by feeding them a Mg2+-deficient diet for 23 days. They were pair-fed to compare with a control group of rats fed a Mg2+-sufficient diet. In the Mg2+-deficient group the plasma total cholesterol and triglyceride levels were increased while HDL-cholesterol was decreased. In the Mg2+-deficient group the plasma level of thiobarbituric acid reacting substances (TBARS) used as a measure for lipid peroxidation was increased. The increase was attributed to the increased cytosolic Ca2+ in Mg2+-deficiency which can cause: 1) increase of hydro and endoperoxide levels as a consequence of the increase of arachidonic acid release and eicosanoid synthesis in Mg2+-deficiency, and 2) inhibition of the mitochondrial respiratory activity and activation of Ca2+-dependent proteases which may activate the conversion of xanthine dehydrogenase to xanthine oxidase which generates active O2 species. In the Mg2+-deficient group, the fatty acid composition of the liver microsomes indicated a slower rate of conversion of linoleic acid to arachidonic acid which was consistent with the decrease of delta 6 desaturase activity in liver microsomes of Mg2+-deficient rats as measured in vitro. The decrease of delta 6 desaturase activity was attributed to the lower concentration of actual enzyme molecules as a result of the decreased rate of protein synthesis in Mg2+-deficiency. The possible effects of the increased catecholamine release in Mg2+-deficiency are discussed.
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PMID:Effect of magnesium deficiency on delta 6 desaturase activity and fatty acid composition of rat liver microsomes. 255 46


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