Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac mitochondrial function as measured by oxidative phosphorylation is impaired by ischemia; and, this deteriorates even further on reperfusion of the heart. Free oxygen radicals, especially the formation of hydroxyl radicals via the iron-catalyzed Haber-Weiss and Fenton reactions have been implicated in the reperfusion injury. In this study, the effect of desferrioxamine (desferal) in the perfusate on mitochondrial function of isolated rat hearts during different periods of normothermic ischemic cardiac arrest (NICA), and subsequent reperfusion was investigated. Mitochondrial functions measured were the QO2 (state 3); ADP/O ratio and oxidative phosphorylation; the mitochondrial, loosely bound (chelateable) iron (LB-iron); the xanthine dehydrogenase and xanthine oxidase activities. Inclusion of desferal in the perfusion solution significantly improved mitochondrial function during the different NICA periods, and prevented the deterioration of mitochondrial function resulting from reperfusion. Desferal did not significantly affect the LB-iron content of the mitochondria or the ratio of xanthine dehydrogenase/xanthine oxidase activities in the mitochondria during NICA or reperfusion. Our experiments suggest that iron, which is free to be chelated by desferal, plays a role in this injury to the rat myocardium.
 ...
PMID:The effect of desferal on rat heart mitochondrial function, iron content, and xanthine dehydrogenase/oxidase conversion during ischemia-reperfusion. 228 9

Incubation of human erythrocytes oxidized by iron catalysts, ADP/Fe3+ or xanthine/xanthine oxidase/Fe3+, with autologous IgG resulted in IgG binding as detected by enzyme immunoassay using protein A-beta-galactosidase conjugate. The binding of autologous IgG to ADP/Fe3(+)-treated erythrocytes maximized when the cells were treated with 1.8:0.1 mM ADP/Fe3+, and declined when treated above this concentration, suggesting that autologous IgG binds to moderately but not to excessively oxidized erythrocytes. The antibody involved in the binding was anti-Band 3, the autoantibody known to bind to aged erythrocytes, because isolated anti-Band 3 bound to the oxidized cells, but anti-Band 3-depleted autologous IgG did not. In addition, purified Band 3 inhibited the autologous IgG binding. Anti-alpha-galactosyl IgG, another natural antibody which has been reported to bind to aged erythrocytes, did not bind to the oxidized cells. Oxidation of membrane lipids, SH-groups of membrane proteins, and Hb of these cells was slight, but the cells contained an increased amount of membrane-bound native Hb, indicating that the oxidized cell membrane has an altered property. alpha-Tocopherol prevented the lipid oxidation and the subsequent IgG binding. Reduction of the oxidized erythrocytes with dithiothreitol resulted in a loss of the IgG binding. These results suggest that anti-Band 3 binding sites (Band 3 senescent antigen) are formed on moderately oxidized erythrocytes as a result of oxidation of membrane protein SH-groups which can be mediated by the membrane lipid oxidation and that formation of the anti-Band 3 binding sites on the oxidized cells is an essentially reversible membrane event which is linked to oxidation and restoration of the protein SH-groups.
 ...
PMID:Binding of anti-band 3 autoantibody to oxidatively damaged erythrocytes. Formation of senescent antigen on erythrocyte surface by an oxidative mechanism. 230 47

Acetylcholine and ATP are costored and coreleased during synaptic activity at the electric organ of Torpedo. It has been suggested that released ATP is converted to adenosine at the synaptic cleft, and in turn this nucleoside would depress the evoked release of acetylcholine. In the present communication we have used a chemiluminescent reaction that let us to monitor continuously the presence of adenosine in this preparation. The chemiluminescent reaction is based on the conversion of adenosine into uric acid and H2O2 by adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase enzymes. The hydrogen peroxide has been detected by peroxidase-luminol mixture. The reaction has a sensitivity on the picomol range and discerned between Adenosine, AMP, ADP, and ATP. We have developed this technique in the hope of understanding whether adenosine is released during synaptic activity or it comes from the released ATP. We have studied the release or formation of adenosine in fragments of the electric organ and in isolated cholinergic nerve terminals obtained from it. In both conditions we have followed the effect of potassium stimulation upon the detection of adenosine. Potassium stimulation increased the extracellular adenosine either in slices or the synaptosomal fraction of Torpedo electric organ. The presence of alpha, beta-methylene ADP, an inhibitor of 5'-nucleotidase, inhibits the detection of adenosine, suggesting that extracellular adenosine is a consequence of ectocellular dephosphorylation of released ATP.
 ...
PMID:The release of adenosine at the electric organ of Torpedo. A study using a continuous chemiluminescent method. 232 27

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.
 ...
PMID:Histamine release in acute coronary occlusion-reperfusion in isolated guinea-pig heart. 245 99

The poly(ADP-ribosylation) of chromosomal proteins is an epigenetic consequence of clastogenic DNA damaging agents which affects chromatin structure and function. We studied the poly(ADP-ribosylation) of the major classes of histones in response to DNA breakage induced by an extracellular burst of active oxygen (AO) or the alkylating agent N-methyl-N'-nitrosoguandine (MNNG) in the immortalized human keratinocytes HaCa T using a combination of affinity chromatography on phenylboronate resin and immunoblotting with polyclonal antibodies against histones H1, H2B, H2A, H3, and H4. The following findings characterized the poly(ADPR) reaction: (1) pretreatment of nuclear extracts with snake venom phosphodiesterase which removes poly(ADPR) chains strongly reduced the material which was retained by phenylboronate; (2) the ADPR transferase inhibitor benzamide (100 microM) suppressed AO-induced poly(ADP-ribosylation); (3) poly(ADP-ribosylation) reduced the electrophoretic mobility of the modified histones. Several histones were constitutively poly(ADP-ribosylated) in untreated controls: 0.03% of H2A, 0.04-0.06% of H2B, and 0.04% of H3.1 carried at least one poly(ADPR) chain of undetermined length. AO transiently increased the poly(ADPR) levels of all major histones with the exception of H1. The extent of substitution 30 min after exposure to AO generated by 50 micrograms/mL xanthine and 5 micrograms/mL xanthine oxidase was 0.8% for A24 greater than 0.3% for H4 greater than 0.1% for H3.1 = 0.1% for H3.2 = 0.1% for H2B.2 greater than 0.09% for H2A. Within 60 min, poly(ADPR) substitution had decreased to control levels for H3 and H4 and below control levels for H2A and H2B.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Poly(ADP-ribosylation) of histones in intact human keratinocytes. 247 78

The effects of a reactive oxygen system on axonal conduction were assessed in an in vitro rat spinal cord preparation. An enzyme system, containing hypoxanthine and xanthine oxidase as a source of superoxide and hydrogen peroxide, was used in combination with ADP and FeCl3 as catalysts for peroxidative activity. The reactants were mixed as they entered a temperature-controlled Plexiglas chamber containing a longitudinal hemisection of adult rat spinal cord. Extracellular action potentials were recorded with a glass microelectrode before, during, and after the exposure. A significant conduction block developed during the 30 min exposure. Action potential amplitude decreased to less than 45% of pre-exposure level while absolute refractory period to paired stimuli increased 160%. Following reintroduction of normal bathing medium, amplitude and absolute refractory period exhibited recovery toward pre-exposure control levels, but did not fully recover. Isolated spinal cord membranes exposed to the same xanthine oxidase system produced significant levels of malondialdehyde (MDA). Superoxide dismutase (SOD), but not catalase, effectively inhibited MDA production. Hypoxanthine, xanthine oxidase, and ADP-Fe3+ were all required to induce conduction block in the spinal cord and peroxidation in the isolated membranes. However, addition of intermediate scavengers, SOD and catalase, alone or in tandem, did not prevent the conduction block. Mechanisms other than radical-induced lipid peroxidation may be working to alter the membrane ionic equilibrium in the cord preparation.
 ...
PMID:In vitro spinal cord conduction block during exposure to a xanthine oxidase/hypoxanthine system: noninvolvement of superoxide and hydrogen peroxide. 254 77

It has been proposed that a major target organelles damaged by the ischemic process, probably by the oxygen free radicals generated, is the portion of the excitation-contraction coupling system that regulates Ca2+ delivery (the sarcoplasmic reticulum and sarcolemma) to the contractile proteins. We tested this hypothesis by studying the effect of in vitro generation of oxygen free radicals from xanthine-xanthine oxidase system or dihydroxyfumarate (DHF)/Fe3+-ADP system on Ca2+ flux behavior of canine cardiac sarcoplasmic reticulum (SR); sarcolemmal (Na+, K+)-ATPase and Na+-Ca2+ exchange activities; and myofibrillar (Ca2+, Mg2+)-ATPase activity. Generation of oxygen free radicals by xanthine oxidase acting on xanthine as a substrate increased the passive Ca2+ efflux and decreased intravesicular Ca2+ with no effect on active Ca2+ influx (Ca2+-ATPase) of SR vesicles. Similar exposure of sarcolemmal vesicles to xanthine plus xanthine oxidase stimulated Na+-Ca2+ exchange activity. When sarcolemmal vesicles were incubated with DHF plus Fe3+-ADP, (Na+, K+)-ATPase activity was decreased. It is postulated that the SR Ca2+ efflux pathways but not catalytic activity of the Ca2+ pump and sarcolemmal (Na+, K+)-ATPase involving Na+-Ca2+ exchange activity are altered by oxygen free radicals, and such changes may partly account for the occurrence of intracellular Ca2+ overload during the course of myocardial ischemia. Interestingly, oxygen free radicals from xanthine-xanthine oxidase system had no effect on myofibrillar pCa-ATPase curve. From this set of observations we would hypothesize that the SR and sarcolemma may be the principal target organelles of oxygen free radicals attack in the ischemic injury and not the contractile proteins per se.
 ...
PMID:Possible mechanism responsible for mechanical dysfunction of ischemic myocardium: a role of oxygen free radicals. 255 60

Despite efficient revascularisation procedures for vascular disease, the limb can occasionally be lost following reperfusion. One contributing factor might be the formation of oxygen free radicals. This study attempts to describe the conditions necessary for oxy-radical formation from adenine nucleotide breakdown products and the role of plasma creatine content as a marker of cellular injury. Twelve patients undergoing aortic reconstructive surgery were studied. Only partial ischaemia of the lower limbs was induced by the aortic clamping, since varying degrees of collateral circulation existed. Radial arterial and external iliac venous blood was obtained simultaneously before, during and after cross-clamping of the aorta, and plasma levels of ATP, ADP, hypoxanthine, phosphocreatine, creatine, creatinine and lactate measured using luminescence and spectrophotometry. Venous creatine content increased during ischaemia and was doubled 30 min after recirculation. This increase was possibly due to leakage following cellular injury agreeing with a previously observed decrease in muscle tissue creatine content. The iliac arterio-venous difference of hypoxanthine and lactate markedly increased immediately post-ischaemia, while the phosphocreatine difference decreased. Plasma hypoxanthine was abundant in the leg on reoxygenation. The existence of a xanthine oxidase system in skeletal muscle could produce favourable conditions for oxy-radical formation through hypoxanthine degradation, which may contribute to the known muscle tissue injury.
 ...
PMID:Plasma metabolic disturbances and reperfusion injury following partial limb ischaemia in man. 271 61

Using paraquat, adriamycin, and anthraquinone 6-sulfonate, we have investigated the ability of radical-driven Fenton reactions to oxidize formate or deoxyribose when catalyzed by iron complexed with citrate, ADP, ATP, or pyrophosphate. Radicals were generated either radiolytically or enzymatically with xanthine oxidase or ferredoxin reductase. With each radical source, the citrate, ADP, and ATP complexes were at least 50% as active as Fe(EDTA) at catalyzing deoxyribose oxidation, and slightly less active as catalysts of CO2 formation from formate. Fe(pyrophosphate) was less efficient and in some cases inactive. Although it is not possible to definitively identify the oxidant involved, it behaved more like the hydroxyl radical than the proposed ferryl or peroxoferrous species formed in equivalent reactions catalyzed by nonchelated iron, which can oxidize deoxyribose but not formate. Chelator concentrations of 1-2 mM were required for maximum effect, which implies that the major effect of the chelators is on the reactivity of Fe2+ in the Fenton reaction with H2O2. This also suggests that any iron available physiologically could participate in the Fenton reaction in a nonchelated form, and produce a ferryl species rather than the hydroxyl radical. Reactions of the organic radicals contrast with the equivalent reactions of superoxide (Haber-Weiss reaction) for which the same iron chelates are all very inefficient catalysts. Fenton reactions driven by organic reducing radicals may therefore contribute more to the toxicity of redox cycling compounds than equivalent reactions of superoxide.
 ...
PMID:Radical-driven Fenton reactions: studies with paraquat, adriamycin, and anthraquinone 6-sulfonate and citrate, ATP, ADP, and pyrophosphate iron chelates. 282 82

Our recent studies have indicated that release of ATP/ADP from platelets causes enhanced O2-. responses in stimulated neutrophils. The current investigations were designed to provide further details of this phenomenon, to determine the structure-function correlates of the adenine compounds, and to assess if the results might be explained by the formation of a single metabolic product of ATP. ATP, ADP, AMP and adenosine enhanced O2-. responses of rat neutrophils stimulated with immune complexes or formyl chemotactic peptide (FMLP) but had no effect on responses of phorbol ester-stimulated neutrophils. Similar results were obtained in human neutrophils stimulated with immune complexes; when FMLP was the agonist, the results were divergent: ATP and ADP enhanced the responses, whereas AMP and adenosine were inhibitory. In structure-function studies, hydrolytically resistant forms of ATP (and other adenine nucleotides) containing blocked or cross-linked phosphate groups were active, suggesting that hydrolysis of these compounds to a common metabolic product is not required for their effects on O2-. responses. In contrast, other chemical modifications of the ribose ring or adenine base of ATP resulted in greatly diminished activity. To further pursue the question of whether metabolism of the adenine compounds via the adenosine pathway was related to the observed effects on O2-. responses, addition to rat neutrophils of inhibitors of adenosine deaminase, S-adenosyl homocysteine hydrolase, or xanthine oxidase failed to reproduce or augment the enhancement effects of the adenine compounds on O2-. responses, suggesting that metabolism of the adenine compounds to a common product may not be a requirement for the observed effects. Although the manner by which the adenine compounds affect O2-. responses is not known, the data suggest that adenosine and adenine nucleotides have important regulatory effects on oxygen radical responses of stimulated neutrophils.
 ...
PMID:Regulatory effects of adenosine and adenine nucleotides on oxygen radical responses of neutrophils. 283 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>