Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Oil emulsion and raw and cooked tissue homogenates were used to determine the mechanisms of various iron forms on the catalysis of lipid peroxidation. Flax oil (0.25 g) was blended with 160 mL maleate buffer (0.1 M, pH 6.5) to prepare an oil emulsion. Raw or cooked turkey leg meat was used to prepare meat homogenates. Samples were prepared by adding iron from each of the various sources, reactive oxygen species, or enzyme (xanthine oxidase and superoxide dismutase) systems into the oil emulsion or meat homogenates. In oil emulsion and cooked-meat homogenates, ferrous iron and hemoglobin had strong prooxidant effects, but ferritin became prooxidant only when ascorbate was present. Hemoglobin and ferritin had no prooxidant effect in raw-meat homogenates. The status of heme iron and the released iron from hemoglobin had little effect on the prooxidant effect of hemoglobin in oil emulsion and cooked meat homogenate systems. The prooxidant effect of ferrous iron in oil emulsion and cooked-meat homogenates disappeared in the presence of superoxide (.O2-), H2O2, or xanthine oxidase systems. In raw-meat homogenates, however, ferrous had strong prooxidant effects even in the presence of .O2-, or H2O2. The status of free iron was the most important factor in the oxidation of oil emulsion and cooked-meat homogenates but the impact in raw-meat homogenates was small.
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PMID:Prooxidant effects of ferrous iron, hemoglobin, and ferritin in oil emulsion and cooked-meat homogenates are different from those in raw-meat homogenates. 949 4

Iron may be important in catalyzing excessive production of reactive oxygen species (ROS). Cellular iron homeostasis is regulated by iron regulatory proteins (IRPs), which bind to iron-responsive elements (IRE) of mRNAs for ferritin and transferrin receptor (TfR) modulating iron uptake and sequestration, respectively. Although iron is the main regulator of IRP activity, IRP is also influenced by other factors, including the redox state. Therefore, IRP might be sensitive to pathophysiological alterations of redox state caused by ROS. However, previous studies have produced diverging evidence on the effect of oxidative injury on IRP. Results obtained in an animal model close to a pathophysiological condition, such as ischemia reperfusion of the liver as well as in a cell-free system involving an enzymatic source of O2 and H2O2, indicate that IRP is downregulated by oxidative stress. In fact, IRP activity is inhibited at early times of post-ischemic reperfusion. Moreover, the concerted action of O2 and H2O2 produced by xanthine oxidase in a cell-free system caused a remarkable inhibition of IRP activity. IRP seems a direct target of ROS; in fact, in vivo inhibition can be prevented by the antioxidant N-acetylcysteine and by interleukin-1 receptor antagonist. In addition, modulation of iron levels of the cell-free assay did not affect the downregulation imposed by xanthine oxidase. Conceivably, downregulation of IRP activity by O2 and H2O2 may facilitate iron sequestration into ferritin, thus limiting the pro-oxidant challenge of iron.
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PMID:Effect of reactive oxygen species on iron regulatory protein activity. 966 19

Mechanisms of superoxide.O2--generating systems on the pro-oxidant effect of iron from various sources were studied. Reaction mixtures were prepared with distilled water, oil emulsion, or meat homogenates. Free ionic iron (ferrous and ferric), ferritin and hemoglobin (Hb) were used as iron sources, and KO2 and xanthine oxidase (XOD) systems were used to produce .O2-. Thiobarbituric acid reactive substances (TBARS) values and iron contents of the reaction mixtures were determined. Ferric iron and ferritin, in the presence or absence of superoxide-generating systems, had no catalytic effect on the oxidation of oil emulsion but became pro-oxidants when reducing agent (ascorbate) was present. Ferrous iron and Hb had strong catalytic effects on the oxidation of oil emulsion as shown by TBARS values. Superoxide and H2O2, generated from superoxide-generating systems, oxidized ferrous iron and ascorbate, and lowered the pro-oxidant effect of ferrous iron in oil emulsion. Addition of ferric or ferrous iron increased but Hb did not have any effect on the TBARS values of raw meat homogenates. The reaction mechanisms of superoxide and the superoxide-generating systems on the prooxidant effect of various iron sources indicated that .O2- was a strong oxidizer rather than a reducing agent, and the antioxidant effect of XOD system in oil was caused by the oxidation of ferrous iron to the ferric form by .O2- and/or H2O2.
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PMID:Effect of superoxide and superoxide-generating systems on the prooxidant effect of iron in oil emulsion and raw turkey homogenates. 973 34

Ferritin, the major iron storage protein in mammalian cells, was treated with various concentrations of different oxidants: xanthine/xanthine oxidase, Sin-1 (3-morpholinosydnonimine, purchased from Alexis, Grunberg, Germany), DEA-NO (Diethylamine NONOate, purchased from Calblochem-Novabiochem, Schwalbach, Germany), and hydrogen peroxide. The proteolytic susceptibility towards the isolated 20S proteasome of untreated ferritin and oxidized ferritin was measured in parallel with the iron liberated by these oxidants. With increasing hydrogen peroxide, Sin-1, and xanthine oxidase concentrations, the measured proteasomal degradation of ferritin also increased. At higher oxidant concentrations, however, the proteolytic susceptibility began to decrease. The oxidation of ferritin by DEA-NO was accompanied by a lesser increase of proteolytic susceptibility in comparison with the effects of the other oxidants. Addition of DEA-NO to Sin-1 suppressed the increase in proteolytic susceptibility of ferritin, whereas adding xanthine/xanthine oxidase had no additional effect. Iron was liberated readily from ferritin as a result of the oxidation process, although the increase in proteolytic susceptibility was not always correlated to the iron release. In fact, the degradation of oxidatively damaged ferritin was not accompanied by a further increase of free iron. Therefore, we conclude that the proteasome is a secondary antioxidative defense system that degrades only nonfunctional ferritin.
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PMID:Ferritin oxidation in vitro: implication of iron release and degradation by the 20S proteasome. 1090 78

The involvement of "free" iron in damage caused by oxidative stress is well recognized. Superoxide generated in a short burst and at a relatively high flux by the xanthine/xanthine oxidase couple is known to release iron from ferritin in the presence of phenanthroline derivatives as iron chelators. However, superoxide generation via xanthine oxidase is accompanied by the simultaneous direct generation of hydrogen peroxide and, in the presence of ferritin, there is also a superoxide-independent release of iron. In this study it was found that the iron chelator employed attenuates superoxide formation from the xanthine/xanthine oxidase couple. The reaction of ferritin and transferrin with a clean chemical source of superoxide, di(4-carboxybenzyl)hyponitrite (SOTS-1) was therefore investigated. The efficiency of superoxide-induced iron release from ferritin increases dramatically as the superoxide flux is decreased, reaching as high as 0.5 Fe per O2*-. Treatment of ferritin for 16 h with SOTS-1 yielded as many as 130 Fe atoms/ferritin molecule, which greatly exceeds the amount of possible "contaminating" iron absorbed on the protein shell.
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PMID:Effect of a prolonged superoxide flux on transferrin and ferritin. 1106 77

Superoxide dismutase exerted a pronounced inhibitory effect upon xanthine oxidase-mediated reduction of iron in ferritin, ferric chloride, or ferric ADP. Maximal inhibition was observed when the superoxide dismutase concentration was only about 1% of that found in normal porcine liver. These observations indicate that superoxide anion radical is an intermediate in the reduction of iron by xanthine oxidase in vitro but not in vivo.
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PMID:The role of superoxide anion radical in the reduction of ferritin iron by xanthine oxidase. 1134 83

Exposure of proteins to oxidants leads to increased oxidation followed by preferential degradation by the proteasomal system. The role of the biologically occurring oxidants singlet oxygen and peroxynitrite in oxidation of proteins in living cells and enhanced degradation of these proteins was examined in this study. Subsequent to treatment of an isolated model protein, ferritin, with singlet oxygen or peroxynitrite, there was enhanced degradation by the isolated 20S proteasome. Treatment of clone 9 liver cells (normal liver epithelia) with two different singlet oxygen-generating systems or peroxynitrite leads to a concentration-dependent increase in cellular protein turnover. At high concentrations of these oxidants, the protein turnover decreases without significant loss of cell viability and proteasome activity. To compare the increase of intracellular protein turnover with that obtained with other oxidants, cells were exposed to hydrogen peroxide or xanthine/xanthine oxidase. The maximal increase in protein turnover was similar with the various oxidants. The oxidized protein moieties were removed by enhanced protein turnover. Removal of singlet oxygen- or peroxynitrite-damaged proteins is dependent on the proteasomal system, as suggested by the sensitivity to lactacystin. Our results provide evidence that the proteasomal system is able to selectively recognize and degrade proteins modified by singlet oxygen or peroxynitrite in vitro as well as in living cells.
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PMID:Protein oxidation and proteolysis by the nonradical oxidants singlet oxygen or peroxynitrite. 1136 22

Aminoacetone (AA) is a threonine and glycine catabolite long known to accumulate in cri-du-chat and threoninemia syndromes and, more recently, implicated as a contributing source of methylglyoxal (MG) in diabetes mellitus. Oxidation of AA to MG, NH(4)(+), and H(2)O(2) has been reported to be catalyzed by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by Cu(II) ions. We here study the mechanism of AA aerobic oxidation, in the presence and absence of iron ions, and coupled to iron release from ferritin. Aminoacetone (1-7 mM) autoxidizes in Chelex-treated phosphate buffer (pH 7.4) to yield stoichiometric amounts of MG and NH(4)(+). Superoxide radical was shown to propagate this reaction as indicated by strong inhibition of oxygen uptake by superoxide dismutase (SOD) (1-50 units/mL; up to 90%) or semicarbazide (0.5-5 mM; up to 80%) and by EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which detected the formation of the DMPO-(*)OH adduct as a decomposition product from the DMPO-O(2)(*)(-) adduct. Accordingly, oxygen uptake by AA is accelerated upon addition of xanthine/xanthine oxidase, a well-known enzymatic source of O(2)(*)(-) radicals. Under Fe(II)EDTA catalysis, SOD (<50 units/mL) had little effect on the oxygen uptake curve or on the EPR spectrum of AA/DMPO, which shows intense signals of the DMPO-(*)OH adduct and of a secondary carbon-centered DMPO adduct, attributable to the AA(*) enoyl radical. In the presence of iron, simultaneous (two) electron transfer from both Fe(II) and AA to O(2), leading directly to H(2)O(2) generation followed by the Fenton reaction is thought to take place. Aminoacetone was also found to induce dose-dependent Fe(II) release from horse spleen ferritin, putatively mediated by both O(2)(*)(-) and AA(*) enoyl radicals, and the co-oxidation of added hemoglobin and myoglobin, which may be viewed as the initial step for potential further iron release. It is thus tempting to propose that AA, accumulated in the blood and other tissues of diabetics, besides being metabolized by SSAO, may release iron and undergo spontaneous and iron-catalyzed oxidation with production of reactive H(2)O(2) and O(2)(*)(-), triggering pathological responses. It is noteworthy that noninsulin-dependent diabetes has been frequently associated with iron overload and oxidative stress.
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PMID:Aerobic oxidation of aminoacetone, a threonine catabolite: iron catalysis and coupled iron release from ferritin. 1155 49

Iron, through its participation in reactions that generate reactive oxygen species, may contribute to the oxidative lung injury observed in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A number of investigators have shown that the endogenous iron storage protein ferritin increases in the blood of patients with and at-risk for ALI and ARDS, but the significance of these increases are not known. In the present investigation, we measured lung tissue levels of thiobarbituric acid reactive substances (TBARS) and lung leak in isolated rat lungs perfused with xanthine oxidase (XO) and purine, an enzymatic system which generates reactive oxygen species. We found that adding ferritin (100 ng/mL) or desferrioxamine (DFO, 10 mM), an iron chelator, to the vascular perfusate solution decreased oxidant-induced leak in isolated rat lungs perfused with XO and purine. Addition of ferritin or DFO also decreased TBARS in isolated rat lungs perfused with XO and purine; neither ferritin nor DFO, however, decreased XO activity in vitro. Our results suggest that oxidative lung leak may be altered by the availability of reactive iron and that ferritin may contribute to protection against oxidative lung injury.
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PMID:Ferritin and desferrioxamine attenuate xanthine oxidase-dependent leak in isolated perfused rat lungs. 1218 28

The novel antioxidant 3-O-caffeoyl-one-methylquinic acid (MCGA3) is a methyl chlorogenic acid derivative isolated from bamboo leaves. MCGA3 scavenges reactive oxygen species (ROS) and inhibits lipid peroxidation and xanthine oxidase in vitro. In this study, we evaluated the cytoprotective effect of MCGA3, which occurs via heme oxygenase-1 (HO-1) induction in bovine vascular endothelial cells exposed to tert-butylhydroperoxide (tBHP). Cells treated with 1 mM tBHP (6-18 h) generated substantial ROS and concomitantly lost most intracellular lactate dehydrogenase (LDH), which then caused necrotic cell death. Of the several MCGA antioxidants and structurally related phenolic acids examined in this study, MCGA3 (0.01-0.15 mM) was found to completely block this necrosis and generation of ROS by tBHP. Surprisingly, MCGA3 by itself was found to be a potent inducer of HO-1. We observed the time- and dose-dependent induction of HO-1 mRNA and protein, which was closely associated with decreased intracellular ROS and necrosis against tBHP. Deesterified or Al-chelated MCGA3 or co-treatment with MCGA3 and actinomycin D abolished HO-1 induction and the antinecrotic effect of MCGA3. Zinc protoporphyrin IX and cycloheximide attenuated the cytoprotection afforded by MCGA3, but did not reduce HO-1 mRNA. Interestingly, N-acetylcysteine (1 mM) enhanced the HO-1 induction of MCGA3, but N-acetylcysteine itself did not induce HO-1. These results suggested that not only ortho-dihydroxyl groups but also aromatic ester and methoxyl ester moieties are necessary for full HO-1 induction and cytoprotection against toxic tBHP-derived ROS. Ferritin mRNA was also upregulated during all HO-1 induction by MCGA3, which might decrease iron and lower ROS levels. Consequently, the combined action of HO-1 and ferritin may protect cells from toxic tBHP-mediated necrosis.
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PMID:Cytoprotective effects of heme oxygenase-1 induction by 3-O-caffeoyl-1-methylquinic acid. 1473 89


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