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)

We investigated the effects of superoxide anion on the intracellular free calcium concentration ([Ca2+]i) in human cultured myometrial cells using a calcium-sensitive fluorescent dye, indo-1, and a digital imaging fluorescence microscopic system. Hypoxanthine (HX) plus xanthine oxidase induced a rise in [Ca2+]i in a manner dose-dependent on xanthine oxidase. The increase in [Ca2+]i in the absence of extracellular calcium ([Ca2+]ex) was 10% of that in the presence of [Ca2+]ex. Nifedipine, which blocks voltage-sensitive calcium channels, also reduced the increase in [Ca2+]i induced by HX-xanthine oxidase. Superoxide dismutase or superoxide dismutase plus catalase, which metabolizes superoxide anion, inhibited the effect of HX-xanthine oxidase on [Ca2+]i. The desensitization of the effect of superoxide anion on [Ca2+]i was investigated by pulsatile administration of HX and xanthine oxidase. Desensitization was observed on pulsatile administration of HX-xanthine oxidase at 2-min intervals. These data suggest that superoxide production may participate in uterine contraction via [Ca2+]i increase.
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PMID:Superoxide anion increases intracellular free calcium in human myometrial cells. 217 20

In a retrospective study two patient groups suffering from recurrent calcium oxalate lithiasis are compared before and after antirheumatic therapy using Diclofenac-Natrium alone or in combination with xanthine oxidase inhibitors and/or hydrochlorothiazides. The examination of concentration and excretion of lithogenic important parameters show a partly significant reduction of the concentration mean values of calcium, oxalic acid and uric acid. The influence of non-steroidal antiphlogistics (NSAP) on calculus recurrence rate in calcium oxalate lithiasis is recognized.
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PMID:[Urinary calculus protective side effects of anti-rheumatic therapy]. 237 78

The interactions between lipid peroxidation and calcium in mediating damage to central nervous system membranes have been examined in several in vitro systems. Using isolated rat brain synaptosomes, brain mitochondria, or cultured fetal mouse spinal cord neurons, Ca2+ was found to markedly enhance lipid peroxidation-induced disruption of membrane function. Gamma-aminobutyric acid (GABA) uptake by synaptosomes was inhibited 25% by either lipid peroxidation (induced with xanthine and xanthine oxidase) or Ca2+ alone, whereas inhibition was 46% with their combination. Ca2+ enhancement of lipid peroxidation-induced damage to synaptosomes was intensified by the Ca2+ ionophore, A23187, and was partially blocked by the Ca2+ channel blocker, verapamil. Similarly, inhibition of state 3 respiration in isolated rat brain mitochondria was observed with Ca2+ and a free radical generating system (xanthine and xanthine oxidase) under conditions where either insult alone failed to cause detectable damage. Na+,K+-ATPase activity of cultured fetal mouse spinal cord neurons was inhibited 32% when cells were incubated for 30 minutes in the presence of both A23187 and a free radical generating system. However, Na+,K+-ATPase was not affected during a 30 minute incubation with either A23187 or radical generating system alone. In further studies, peroxidation of rat brain synaptosomes by ferrous iron (Fe2+) and H2O2 was coupled with a rapid and large (2-7-fold) uptake of Ca2+ by synaptosomes. Fe2+ also enhanced Ca2+ uptake by spinal cord neurons in culture, an effect that was coincident with peroxidation of neuronal membranes and the release of arachidonic acid from cells. Iron-induced Ca2+ uptake was blocked by high concentrations of either desferrioxamine or methylprednisolone, whereas Ca2+ channel blockers did not affect Ca2+ uptake induced by Fe2+. Finally, peroxidation of membrane lipids by Fe2+ was stimulated by Ca2+. Concentrations of Ca2+ as low as 10(-9) M increased peroxidation reactions within brain synaptosomal membranes. The results of these studies indicate that lipid peroxidation and Ca2+ can synergistically act to damage biologic membranes. The findings suggest that Ca2+ and lipid peroxidation cannot be considered as separate entities in the pathophysiology of CNS trauma. A hypothesis proposing an inseparable interplay between lipid peroxidation and Ca2+ in the pathogenesis of traumatic and ischemic cell injury is presented.
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PMID:Interaction of lipid peroxidation and calcium in the pathogenesis of neuronal injury. 242 24

It has been shown that plasma histamine significantly increases during myocardial infarction in the dog. Histamine is also released when the isolated guinea-pig heart is reperfused after 30 minutes of low flow perfusion. The release of histamine and lactate dehydrogenase (LDH) after left anterior descending coronary artery ligation and release were investigated in the present study and related to the changes in electrocardiographic parameters and to a computer-aided analysis of left ventricular mast cell metachromasia. Spontaneous release of histamine was unchanged during ischemia and increased after the release of the ligature, while we observed a steady increase of LDH overflow. In parallel, a significant diminution of mast cell granule metachromasia was observed in left ventricular samples. The perfusion of the heart with FeCl3/ADP (10 microM/100 microM), a free radical-generating system, significantly enhanced both the basal and ischemic-reperfusion release of histamine, while perfusion with N-t-butyl-phenyl-nitrone (BPN/100 microM) a "spin-trapper" molecule, significantly decreased histamine and LDH release and the loss in metachromasia of left ventricular mast cells induced by reperfusion. Inhibitors of xanthine oxidase (allopurinol, 10 microM) and of calcium-activated proteases (leupeptin, 10 microM) modified the kinetics of histamine and LDH release.
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PMID:Histamine release in acute coronary occlusion-reperfusion in isolated guinea-pig heart. 245 99

Reaction conditions for determining the activity of purine nucleoside phosphorylase (PNP; E.C. 2.4.2.1) were investigated. We examined the kinetic parameters for the enzymatic reaction with respect to the substrates inosine and phosphate. We confirmed the pH optimum, established the optimal concentration of xanthine oxidase and that of calcium and magnesium. The Km values for inosine and phosphate were found to be 60 uM and 667 uM, respectively. Optimum assay conditions for PNP activity were established. This optimized method has been compared with other procedures and found to be more sensitive and to yield significantly higher activities. The experimental variation of a manual procedure using these optimum reaction conditions was less than 4.5%. The mean erythrocyte PNP activity of 28 healthy subjects was estimated to be 9.71 U/mL packed cells at 25 degrees C and 18.60 U/mL packed cells at 37 degrees C.
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PMID:Purine nucleoside phosphorylase in erythrocytes: determination of optimum reaction conditions. 249 71

The reported presence of covalently bound phosphate residues in flavoproteins has significant implications with regard to the catalytic mechanisms and structural stability of the specific enzymes themselves and in terms of general cellular metabolic regulation. These considerations have led to a reevaluation of the presence of covalently bound phosphorus in the flavoproteins xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.1.3.22) and glucose oxidase (beta-D-glucose: oxygen 1-oxidoreductase, EC 1.1.3.4). Milk xanthine oxidase purified by a procedure that includes anion-exchange chromatography is shown to contain three phosphate residues. All three are noncovalently associated with the protein, two with the FAD cofactor, and one with the molybdenum cofactor. Results of chemical analysis and 31P NMR spectroscopy indicate that enzyme purified by this method contains no phosphoserine residues. Xanthine oxidase preparations purified by chromatography on calcium phosphate gel in place of DEAE-Sephadex yielded higher phosphate-to-protein ratios, which could be reduced to the expected values by additional purification on a folate affinity column. Highly active, highly purified preparations of glucose oxidase are shown to contain only the two phosphate residues of the FAD cofactor. The covalently bound bridging phosphate reported by others may arise in aged or degraded preparations of the enzyme but appears not to be a constituent of functional glucose oxidase. These results suggest that the presence of covalent phosphate residues in other flavoproteins should be rigorously reevaluated as well.
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PMID:Covalently bound phosphate residues in bovine milk xanthine oxidase and in glucose oxidase from Aspergillus niger: a reevaluation. 250 51

We have studied changes in intracellular localization and phosphorylating activity of protein kinase C (PKC) in mouse epidermal JB6 cells treated with oxidants. Exposure to hydrogen peroxide, reagent grade or generated enzymatically by glucose/glucose oxidase, at concentrations known to result in elevated intracellular free Ca2+ resulted in an increase in binding of [3H]phorbol dibutyrate to intact cells. Ca2+ chelation, either intracellularly by quin 2 or extracellularly by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, abolished the increase in radioligand binding. In contrast to H2O2, superoxide generated extracellularly by xanthine/xanthine oxidase or intracellularly by menadione was inactive. Scatchard plot analysis revealed that the enhancement in binding resulted from both increased receptor affinity and increased maximal binding capacity. Treatment of cells with superoxide, generated extracellularly by xanthine/xanthine oxidase or intracellularly by menadione, diminished the [3H]phorbol dibutyrate-binding capacity of the cytosol fractions prepared at low Ca2+ concentration. This decrease was not accompanied by a compensatory increase in the binding to membrane components. In contrast to superoxide, reagent H2O2, H2O2 produced by glucose/glucose oxidase, and the Ca2+ ionophore A23187 had no significant effect on the [3H]phorbol dibutyrate-binding capacities of either cellular fraction. Exposure of cells to low concentrations of extra- or intracellular superoxide resulted in an increase in the Ca2+- and phospholipid-dependent phosphorylating activity of cytosolic extracts towards adenosine diphosphoribose transferase which has been reported to be a specific substrate for PKC. The increase in phosphorylation could be diminished by the extracellular addition of copper-zinc-containing superoxide dismutase but not catalase suggesting that superoxide rather than H2O2 represents the active oxygen species in this reaction. The observation that reagent H2O2 or glucose/glucose oxidase failed to increase the phosphorylating activity of cytosolic preparations supports this conclusion. Treatment of cells or cytosolic extracts with the sulfhydryl reagent diamide stimulated the Ca2+/phospholipid-dependent phosphorylating activity toward adenosine diphosphoribose transferase. In a reconstituted system containing purified PKC, diamide induced a 25-30% increase in phospholipid-dependent phosphorylation of H1 whereas no change in activity was observed with the reducing agent dithiothreitol. It is concluded that H2O2 but not superoxide induces an increase in the phorbol ester binding, presumably to PKC, of intact JB6 cells. On the other hand
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PMID:Translocation and enhancement of phosphotransferase activity of protein kinase C following exposure in mouse epidermal cells to oxidants. 250 33

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


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