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

Experiments were performed to determine if xanthine oxidase is a source of free radicals during myocardial ischemia. Open chest dogs were subjected to 1 h of total occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Directly after coronary artery occlusion, Ce141 microspheres were injected into the left atrium to mark the ischemic bed. At the end of reperfusion, the hearts were removed and sectioned. Autoradiography determined the ischemic myocardium at risk, and the necrotic zone was determined by triphenyl-tetrazolium staining. Animals were divided into three groups: control, allopurinol (24-h oral pretreatment 400 mg, then 50 mg/kg IV bolus on occlusion); and superoxide dismutase starting with occlusion (15 000 U/kg). The size of the infarct as a percentage of the tissue at risk was: 23.1 +/- 4.1 for the control; 8.7 +/- 1.2 for the allopurinol group; and 5.4 +/- 1.2 for the superoxide dismutase group. The infarcts in the allopurinol and superoxide dismutase groups were significantly smaller than those in the control groups. In a second series of experiments we determined the xanthine oxidase/xanthine dehydrogenase content of dog myocardium. The left anterior descending branch was ligated for 30 min and then biopsies were removed from both the normal and the ischemic regions. Total enzyme content did not differ between the two regions averaging 0.259 U/g protein for the ischemic tissue and 0.225 U/g protein for the normal region. Only 9.8% of the enzyme was in the oxidase form in the normal region while 32.8% was in the oxidase form in the ischemic zone.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1985 Feb
PMID:Xanthine oxidase as a source of free radical damage in myocardial ischemia. 383 24

To explore the susceptibility of the extracellular protozoan, Entamoeba histolytica, to toxic oxygen intermediates, trophozoites were exposed to fluxes of O2, H2O2, and OH. generated enzymatically by the glucose oxidase and xanthine oxidase reactions. HM-1 trophozoites were resistant to O2, but were readily killed by H2O2 alone. OH. and 1O2 were not required for effective amebicidal activity. The addition of peroxidase and halide enhanced trophozoite killing by H2O2. Sonicates of amebae contained virtually no catalase and little glutathione peroxidase activity which may contribute to susceptibility to H2O2. Coupled with our previous studies with Toxoplasma gondii and Leishmania spp. these observations indicate that there is a broad spectrum of susceptibility of intra- and extracellular pathogenic protozoa to killing by oxygen intermediates.
Mol Biochem Parasitol 1981 Oct
PMID:Susceptibility of Entamoeba histolytica to oxygen intermediates. 627 8

Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.
J Mol Cell Cardiol 1983 Oct
PMID:Production of free radicals and lipid peroxides in early experimental myocardial ischemia. 631 60

Previous research has shown that heart mitochondria are able to produce reactive species of oxygen such as superoxide radicals, hydrogen peroxide and hydroxyl radicals [10, 11]. When these compounds are formed beyond a certain level they are not completely removed by the enzymatic and metabolic processes which neutralize their toxicity, and as a result they are able to produce structural and functional damages that impair mitochondrial function [5, 10]. In order to study the molecular mechanism/s by which the oxygen radicals may function as mediators of cellular injury a flow of these radicals by chemical, enzymatic or photochemical methods has been generated in vitro in the presence of cellular preparations. For example, the exposure of isolated subcellular particles to the enzymatic flow of oxygen radicals produced by the reaction of xanthine oxidase upon xanthine reduced both calcium uptake velocity and Ca2+-ATPase activity in sarcoplasmic reticulum [7], while it reduced Ca2+-stimulated ATPase activity in myofibrillar preparations [4]. In addition, incubation with the xanthine oxidase reaction produced an impairment of the respiratory functions associated with an increased lipid peroxidation in the isolated mitochondria [5, 10]. These negative effects were augmented in alpha-tocopherol-deficient mitochondria [3], but were opposed by the exogenous addition of superoxide dismutase [10]. This report shows that the superoxide radicals generated by the xanthine oxidase reaction reduced rat heart mitochondrial respiration induced by pyruvate. This negative effect was partially prevented by superoxide dismutase and catalase and by thiol protecting agents. Moreover, the generation of free radicals caused a significant reduction in the rate of (1-14C) -pyruvate decarboxylation, while it did not change the transport of pyruvate into mitochondria.
J Mol Cell Cardiol 1983 Dec
PMID:Effect of superoxide generation on rat heart mitochondrial pyruvate utilization. 631 22

Phenazine methosulfate, a cationic electron carrier, inhibits the extracellular growth of promastigotes and the conversion of amastigotes into promastigote forms of Leishmania mexicana amazonensis. Growth inhibition and damage of extracellular parasites by PMS was counteracted by superoxide dismutase, a scavenger of the superoxide anion (O2-), and to a lesser extent, by catalase, a scavenger of hydrogen peroxide (H2O2). Inactivated dismutase and catalase were ineffective. Thus, damage of isolated L.m. amazonensis by phenazine methosulfate, involves the participation of O2- and H2O2. The role of the oxygen metabolites in the toxicity of phenazine methosulfate remains unknown. That O2- can damage the parasites is supported by the finding that superoxide dismutase also protected promastigotes from damage induced by oxygen intermediates generated by a xanthine-xanthine oxidase system. Killing of the parasites by crystal violet, a triphenylmethane, or basic blue 24, a phenothiazine, was not inhibited by superoxide dismutase.
Mol Biochem Parasitol 1984 Mar
PMID:Inhibition by superoxide dismutase and catalase of the damage of isolated Leishmania mexicana amazonensis by phenazine methosulfate. 632 96

We strongly support the original intriguing hypothesis of Hearse et al. that the oxygen paradox and the calcium paradox are facets of the same problem. We would propose that the major similarity is a final common pathway leading to intracellular calcium overload and the sequelae of the resultant increase in intracellular calcium. In addition, we would propose that the oxygen paradox and ischemic/reperfusion injury are also facets of the same problem with the major similarity being the reintroduction of molecular oxygen to a previously hypoxic myocardium. Finally, we would suggest that the common pathway leading to intracellular calcium overload in the oxygen paradox and ischemic/reperfusion injury and to a lesser extent the calcium paradox involves the generation of oxygen free radicals. The source of oxygen free radical generation in the calcium paradox is perhaps less obvious than in the oxygen paradox. It is proposed that during calcium-free perfusion, calcium is leached from the plasmalemma of the myocyte. There is a resulting increase in membrane fluidity. Within the plasmalemma are a number of calcium sensitive phospholipases. Upon reperfusion with a calcium replete medium, calcium could pool around these membrane bound phospholipases initiating a chain reaction of lipid peroxidation which actually is perpetuated by free radical generation (Equations 5A-5C). Lipid peroxidation opens channels within the plasmalemma rendering a 'leaky' sarcolemma. It is through these channels that calcium could flow down its concentration gradient into the cell. The increased calcium accumulation at the mitochondria would lead to an uncoupling of oxidative phosphorylation. With depleted energy stores, the mitochondria and sarcoplasmic reticulum no longer serve as calcium sinks. This would contribute to the calcium overload seen upon reperfusion. The role of oxygen free radical production would appear to occur during the hypoxic phase of the oxygen paradox and the ischemic phase of ischemic/reperfusion injury and during the reoxygenation/reperfusion phases. With the onset of hypoxia and/or myocardial ischemia there is an increase in reducing equivalents, disturbance and dissociation of intramitochondrial electron transport and release of ubisemiquinone, flavoproteins and superoxide radicals. The increase in reducing equivalents includes NADPH and, in ischemia, catecholamines, hypoxanthine and an increase on xanthine oxidase activity. All of these substrates are capable of participating in free radical production. This increase in free radical production in ischemic tissue is enhanced by acidosis which in the ischemic and hypoxic myocardium approaches pH 6.0-6.4.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Cardiol 1984 Nov
PMID:Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury. 639 65

In order to understand why different stages of Trichinella spiralis vary in their susceptibility to killing by leukocytes, the effects of artificially generated oxidants on different stages of this parasite were compared. More than 90% newborn larvae were killed after incubation in acetaldehyde-xanthine oxidase or glucose-glucose oxidase. On the other hand, fewer than 10% of adult worms or muscle larvae were killed when incubated under identical conditions. Thus, only the stages which are resistant to killing by leukocytes are resistant to killing by oxidants. The larvicidal effect of acetaldehyde-xanthine oxidase was blocked by the addition of either superoxide dismutase or catalase and was partially inhibited by radical scavengers and singlet oxygen quenchers. The oxidant resistant adults and muscle larvae contained 3-5 times more superoxide dismutase and at least five times more glutathione peroxidase than the oxidant sensitive newborn larvae. In contrast, all 3 stages lacked detectable amounts of catalase and contained roughly equivalent amounts of reduced glutathione. Accordingly, adults and muscle larvae may be more resistant to killing by leukocytes than newborn larvae because they contain better oxidant defenses.
Mol Biochem Parasitol 1984 Jan
PMID:Scavenger enzymes and resistance to oxygen mediated damage in Trichinella spiralis. 669 69

Adenosine kinase, adenosine deaminase, hypoxanthine phosphoribosyltransferase, inosine-nucleoside phosphorylase, 5'-AMP deaminase and 5'-IMP nucleotidase were identified in cell-free extracts of duckling erythrocytes; no evidence for 5'-AMP nucleotidase and xanthine oxidase activity was found. The Km values for the duckling red cell enzymes were similar to those reported for human erythrocytes. Plasmodium lophurae extracts demonstrated similar enzyme activities except for 5'-AMP deaminase and 5'-IMP nucleotidase which were absent. It is proposed that during infection erythrocytic AMP is catabolized to IMP, inosine and hypoxanthine; the hypoxanthine is taken up by the plasmodium, utilized to form IMP, and this in turn is converted into adenine and guanine nucleotides.
Mol Biochem Parasitol 1981 Apr
PMID:Purine metabolizing enzymes of Plasmodium lophurae and its host cell, the duckling (Anas domesticus) erythrocyte. 678 22

Xanthine oxidase was purified from bovine milk-fat globule membrane by extraction with butan-1-ol, precipitation with ammonium sulphate, separation by preparative electrofocusing and chromatography on Concanavalin-A/Agarose. The enzyme had an A280/A450 ratio of 4.8 and a specific activity of 3.09. At least five to seven variants of the enzyme with isoelectric points from pH 6.9 to 7.6 were identified. Previously identified minor "variants' of the enzymes with apparently acidic isoelectric points (1) were shown to be the result of aggregation of enzyme with membrane sialoglycoproteins. Specific antibodies to xanthine oxidase were prepared by fractionating immune serum on a column of enzyme covalently bound to Sepharose 4B. A single immunoprecipitate was obtained when the purified antibodies were allowed to diffuse in agarose gels against either Triton-X-100-extracted membrane or purified xanthine oxidase. Immunoelectrophoresis of the enzyme against anti-sera to xanthine oxidase, however, revealed two precipitin lines, both of which were positive when histochemically stained for enzyme activity. The results are discussed with reference to previous purification schemes for xanthine oxidase and previous estimates for the isoelectric points of the enzyme. We also outline practical uses for the antibody prepared against the enzyme in this present study.
Mol Cell Biochem 1982 Apr 16
PMID:Purification of xanthine oxidase from the fat-globule membrane of bovine milk by electrofocusing. 689 60

The Na(+)-K+ ATPase activity and SH group content were decreased whereas malondialdehyde (MDA) content was increased upon treating the porcine cardiac sarcolemma with xanthine plus xanthine oxidase, which is known to generate superoxide and other oxyradicals. Superoxide dismutase either alone or in combination with catalase and mannitol fully prevented changes in SH group content but the xanthine plus xanthine oxidase-induced depression in Na(+)-K+ ATPase activity as well as increase in MDA content were prevented partially. The Lineweaver-Burk plot analysis of the data for Na(+)-K+ ATPase activity in the presence of different concentrations of MgATP or Na+ revealed that the xanthine plus xanthine oxidase-induced depression in the enzyme activity was associated with a decrease in Vmax and an increase in Km for MgATP; however, Ka value for Na+ was decreased. Treatment of sarcolemma with H2O2 plus Fe2+, an hydroxyl and other radical generating system, increased MDA content but decreased both Na(+)-K+ ATPase activity and SH group content; mannitol alone or in combination with catalase prevented changes in SH group content fully but the depression in Na(+)-K+ ATPase activity and increase in MDA content were prevented partially. The depression in the enzyme activity by H2O2 plus Fe2+ was associated with a decrease in Vmax and an increase in Km for MgATP. These results indicate that the depressant effect of xanthine plus xanthine oxidase on sarcolemmal Na(+)-K+ ATPase may be due to the formation of superoxide, hydroxyl and other radicals. Furthermore, the oxyradical-induced depression in Na(+)-K+ ATPase may be due to the formation of superoxide, hydroxyl and other radicals.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem
PMID:Inhibition of cardiac sarcolemma Na(+)-K+ ATPase by oxyradical generating systems. 749 43


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