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)

Low density lipoproteins are highly sensitive to oxidation by copper salts, and such peroxidation is accompanied by macrophage scavenger receptor recognition. This study shows that fresh human atherosclerotic material (aneurysms and endarterectomies) can contain detectable amounts of redox active iron and copper that is chelatable from tissue homogenates. Such material is often prooxidant towards lipid peroxidation and deoxyribose degradation. Aneurysms and endarterectomies contain ferroxidase 1 activities, whereas only in aneurysms could caeruloplasmin be immunologically detected. Ferroxidase 2 activity, characteristic of a copper-oxidised lipoprotein complex, could not, however, be detected in any of the atherosclerotic samples. A third ferroxidase activity, attributable to xanthine oxidase, was present in several aneurysms and endarterectomies.
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PMID:Prooxidant iron and copper, with ferroxidase and xanthine oxidase activities in human atherosclerotic material. 763 10

Xanthine oxidase exhibits ferroxidase activity and previously has been shown to catalyze the oxidative incorporation of iron into apotransferrin, the iron transport protein of plasma. These studies demonstrate that xanthine oxidase also efficiently promotes the oxidative incorporation of iron into apoferritin, the major iron storage protein of vertebrates, and that the ferroxidase activity of intestinal xanthine oxidase could be important in determining the fraction of iron within the intestinal mucosa cell partitioned to ferritin versus the iron that remains in a transient pool for rapid transport to plasma.
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PMID:Xanthine oxidase: an efficient promoter of the iron loading of apoferritin. 795 Oct 57

Exposure of cells to oxygen radicals results in cellular injury and protein oxidation. Ceruloplasmin is a plasma antioxidant that increases in concentration during inflammation. Therefore, the ability of ceruloplasmin to protect endothelial cells from neutrophil-mediated injury was investigated. The inhibition of protein oxidation by ceruloplasmin was also examined in neutrophil and endothelial cell proteins by analysis of carbonyl formation. In addition, the iron oxidation state was measured to determine the effect of ceruloplasmin ferroxidase activity in oxygen-radical generating systems. Ceruloplasmin significantly (p < .01) inhibited neutrophil-mediated cytotoxicity of endothelial cells by 48%. Carbonyl formation in phorbol myristate acetate (PMA)-stimulated neutrophil proteins was also significantly (p < .01) reduced by ceruloplasmin from 0.172 +/- 0.028 to 0.086 +/- 0.004 mole carbonyl/mole protein. Even though ceruloplasmin itself had a threefold increase in carbonyl formation (0.452 +/- 0.010 vs. 0.146 +/- 0.018 mole carbonyl/mole protein) in the presence of PMA-stimulated compared with unstimulated neutrophils, no loss of functional activity was detected. In xanthine oxidase-treated endothelial cells, ceruloplasmin significantly (p < .05) reduced carbonyl formation from 0.132 +/- 0.010 to 0.097 +/- 0.009 mole carbonyl/mole protein. Ceruloplasmin also significantly (p < .01) oxidized iron when added to PMA-activated neutrophils, thereby decreasing Fe(II) from 98 +/- 8 to 7 +/- 2 microM. Similarly, ceruloplasmin added to xanthine oxidase/hypoxanthine reactions resulted in significant (p < .01) iron oxidation, decreasing Fe(II) from 99 +/- 1 to 15 +/- 3 microM. The ability of ceruloplasmin to protect both endothelial cells and endogenous neutrophil and endothelial cell proteins from oxidative injury suggests that it may be important in regulating cellular and protein damage by oxygen radicals during inflammation.
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PMID:Ceruloplasmin inhibits carbonyl formation in endogenous cell proteins. 842 18

Cultured vascular smooth muscle cells (SMC) and endothelial cells (EC) stimulate low density lipoprotein (LDL) oxidation by free radical-mediated, transition metal-dependent mechanisms. The physiological source(s) of metal ions is not known; however, purified ceruloplasmin, a plasma protein containing 7 coppers, oxidizes LDL in vitro. We now show that ceruloplasmin also increases LDL oxidation by vascular cells. In metal ion-free medium, human ceruloplasmin increased bovine aortic SMC- and EC-mediated LDL oxidation by up to 30- and 15-fold, respectively. The maximal response was at 100-300 microg ceruloplasmin/ml, a level at or below the unevoked physiological plasma concentration. Oxidant activity was dependent on protein structure as a specific proteolytic cleavage or removal of one of the seven ceruloplasmin copper atoms inhibited activity. Three lines of evidence indicated a critical role for cellular superoxide (O2.) in ceruloplasmin-stimulated oxidation. First, the rate of production of O2. by cells correlated with their rates of LDL oxidation. Second, superoxide dismutase effectively blocked ceruloplasmin-stimulated oxidation by both cell types. Finally, O2. production by SMC quantitatively accounted for the observed rate of LDL oxidation. To show this, the course of O2. production by SMC was simulated by repeated addition of xanthine and xanthine oxidase to culture medium under cell-free conditions. Neither ceruloplasmin nor O2. alone increased LDL oxidation, but together they completely reconstituted the oxidation rate of ceruloplasmin-stimulated SMC. These results are the first to show that ceruloplasmin stimulates EC- and SMC-mediated oxidation of LDL and that cell-derived O2. accounts quantitatively for metal-dependent, free radical-initiated oxidation of LDL by these cells.
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PMID:Ceruloplasmin enhances smooth muscle cell- and endothelial cell-mediated low density lipoprotein oxidation by a superoxide-dependent mechanism. 866 20

We investigated the generation of nitric oxide (NO) by H2O2-dependent peroxidation of hydroxyurea in the presence of copper-containing proteins such as Cu,Zn-superoxide dismutase (Cu,Zn-SOD) or ceruloplasmin as a catalyst. In the reaction mixture of hydroxyurea, CuZn-SOD, and H2O2, NO generation was identified by measuring the specific electron spin resonance (ESR) signal of 2-phenyl-4, 4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). The ESR signal of the NO-hemoglobin adduct was also detected in human red blood cells during copper-catalyzed peroxidation of hydroxyurea. The NO production during peroxidation of hydroxyurea was quantified as NO2- formation, measured by using the Griess assay, the amount of NO2- was dependent on the concentrating of hydroxyurea of the reaction mixture. ESR spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) showed hydroxy radical (OH) generation in the reaction of H2O2 with either Cu,Zn-SOD or ceruloplasmin. Several OH scavengers, such as ethanol, thiourea, DMPO, and dimethylsulfoxide, and the metalchelating agent diethylenetriaminepentaacetic acid significantly inhibited NO generation from hydroxyurea. This indicates that NO release from hydroxyurea may be mediated by OH derived from the copper-catalyzed Fenton-like reaction. Incubation of hydroxyurea and Cu,Zn-SOD with xanthine oxidase and hypoxanthine in a system forming O2- -->H2O2 also resulted in appreciable NO production. These results suggest that NO production from hydroxyurea catalyzed by copper-containing proteins may be the molecular basis of the pharmacological and antitumor action of hydroxyurea.
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PMID:Nitric oxide generation from hydroxyurea via copper-catalyzed peroxidation and implications for pharmacological actions of hydroxyurea. 947 38

Oxidative modification of low density lipoprotein (LDL) appears to play an important role in atherogenesis. Although the precise mechanisms of LDL oxidation in vivo are unknown, several lines of evidence implicate myeloperoxidase and reactive nitrogen species, in addition to ceruloplasmin and 15-lipoxygenase. Myeloperoxidase generates a number of reactive species, including hypochlorous acid, chloramines, tyrosyl radicals, and nitrogen dioxide. These reactive species oxidize the protein, lipid, and antioxidant components of LDL. Modification of apolipoprotein B results in enhanced uptake of LDL by macrophages with subsequent formation of lipid-laden foam cells. Nitric oxide synthases produce nitric oxide and, under certain conditions, superoxide radicals. Numerous other sources of superoxide radicals have been identified in the arterial wall, including NAD(P)H oxidases and xanthine oxidase. Nitric oxide and superoxide readily combine to form peroxynitrite, a reactive nitrogen species capable of modifying LDL. In this review, we examine the reaction pathways involved in LDL oxidation by myeloperoxidase and reactive nitrogen species and the potential protective effects of the antioxidant vitamins C and E.
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PMID:Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection. 1089 8

This work tested the hypotheses that splanchnic oxidant generation is important in determining heat tolerance and that inappropriate.NO production may be involved in circulatory dysfunction with heat stroke. We monitored colonic temperature (T(c)), heart rate, mean arterial pressure, and splanchnic blood flow (SBF) in anesthetized rats exposed to 40 degrees C ambient temperature. Heating rate, heating time, and thermal load determined heat tolerance. Portal blood was regularly collected for determination of radical and endotoxin content. Elevating T(c) from 37 to 41.5 degrees C reduced SBF by 40% and stimulated production of the radicals ceruloplasmin, semiquinone, and penta-coordinate iron(II) nitrosyl-heme (heme-.NO). Portal endotoxin concentration rose from 28 to 59 pg/ml (P < 0.05). Compared with heat stress alone, heat plus treatment with the nitric oxide synthase (NOS) antagonist N(omega)-nitro-L-arginine methyl ester (L-NAME) dose dependently depressed heme-.NO production and increased ceruloplasmin and semiquinone levels. L-NAME also significantly reduced lowered SBF, increased portal endotoxin concentration, and reduced heat tolerance (P < 0.05). The NOS II and diamine oxidase antagonist aminoguanidine, the superoxide anion scavenger superoxide dismutase, and the xanthine oxidase antagonist allopurinol slowed the rates of heme-.NO production, decreased ceruloplasmin and semiquinone levels, and preserved SBF. However, only aminoguanidine and allopurinol improved heat tolerance, and only allpourinol eliminated the rise in portal endotoxin content. We conclude that hyperthermia stimulates xanthine oxidase production of reactive oxygen species that activate metals and limit heat tolerance by promoting circulatory and intestinal barrier dysfunction. In addition, intact NOS activity is required for normal stress tolerance, whereas overproduction of.NO may contribute to the nonprogrammed splanchnic dilation that precedes vascular collapse with heat stroke.
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PMID:Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. 1115 46

Fibrinogen has been included among the risk factors for vascular disease. Fibrinogen belongs with albumin, ceruloplasmin and transferrin to an acute phase protein group in the plasma. Albumin, ceruloplasmin and transferrin are already recognized as natural antioxidants. In the present study we used three different oxygen generating systems in order to test whether fibrinogen is able to act as an antioxidant in an in vitro system. We used 1) pyrogallol auto-oxidation, 2) the reaction catalysed by xanthine oxidase coupled with the reduction of ferricytochrome c and 3) chemiluminescence. We found that in a dose-dependent manner fibrinogen inhibited superoxide generation (pyrogallol and xanthine-xanthine oxidase reactions), ferrous ion oxidation and hydroxyl radical dependent degradation (of deoxyribose). Fibrinogen also inhibited LDL oxidation (copper and azo compound-induced), hydrogen peroxide oxidation and chemiluminescence produced by polymorphonuclear leukocytes. Fibrinogen, albumin, ceruloplasmin and transferrin act as a supplementary antioxidant defense mechanism against oxidative stress arising from inflammatory conditions.
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PMID:Fibrinogen is an efficient antioxidant. 1125 65

An intraperitoneal injection of an exogenous delta-sleep inducing peptide (DSIP) at a dose of 12 microg/100 g body weight shifted the prooxidant-antioxidant balance of free radical process (FRP) in tissues and erythrocytes of rats: the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and the concentrations of antioxidants (reduced glutathione in particular) increased. The DSIP stimulated the myeloperoxidase activity in blood neutrophils and had no effect on the activity of xanthine oxidase, a prooxidant enzyme, in the brain and liver. Cold stress displaced the prooxidant-antioxidant balance by increasing the xanthine oxidase activity in tissues and decreasing the myeloperoxidase activity in blood neutrophils; it also inhibited the enzyme antioxidant activities in tissues and erythrocytes that was neutralized by an increased ceruloplasmin activity in blood plasma and by an elevated level of antioxidants in rat blood and tissues. Preliminary administration of DSIP to animals exposed to cold stress restored the prooxidant-antioxidant balance: it normalized the myeloperoxidase activity in blood neutrophils, decreased the xanthine oxidase activity, and increased the activity of antioxidant enzymes in tissues and erythrocytes restoring the antioxidant level. The molecular regulation mechanism of free radical processes by DSIP in tissues under stressful conditions is discussed.
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PMID:Regulation of free radical processes by delta-sleep inducing peptide in rat tissues under cold stress. 1142 12

Ceruloplasmin (CP), an important serum antioxidant, is a blue copper glycoprotein with ferroxidase and oxidase activities. Among other physiological actions, plasma CP was shown to protect isolated rat hearts and cultured P19 neurons exposed to oxidative stress conditions, raising the possibility of using this protein in the treatment of cardiac and neuronal diseases related to oxidative damage. However, since therapeutic applications of CP must be compatible with restrictions in the administration of blood derivatives to humans, there is a need to produce the protein by genetic engineering. To help in the choice of adequate expression systems, we undertook this study to determine if the carbohydrate moiety on the protein is essential for its functions. CP was completely deglycosylated using N-glycosidase F under nondenaturing conditions. Deglycosylated CP was found to retain most of the conformational, antioxidant, and enzymatic properties of the native protein in vitro. Moreover, both forms of the protein had similar cardioprotective and neuronoprotective effects against oxidative stress as evaluated with isolated rat hearts undergoing ischemia-reperfusion and with cultured P19 neurons exposed to xanthine-xanthine oxidase. The data thus indicate that the carbohydrate moiety of CP is not essential for its enzymatic and protective actions. Accordingly, even the use of expression systems that do not glycosylate mammalian proteins could provide a recombinant CP that retains its therapeutic potential.
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PMID:Deglycosylated ceruloplasmin maintains its enzymatic, antioxidant, cardioprotective, and neuronoprotective properties. 1152 18


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