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)

Isolated erythrocyte membranes exposed to protease-free xanthine oxidase plus xanthine and ferric iron undergo lipid peroxidation and protein crosslinking (appearance of high molecular weight aggregates on sodium dodecyl sulfate (SDS) gel electrophoresis). Spectrin is more susceptible to crosslinking than the other polypeptides. Thiol-reducible bonds (disulfides) as well as nonreducible bonds are generated, the former type relatively rapidly (detected within 10-20 min) and the latter type more slowly (usually detected after 1 h). Reducible crosslinking is inhibited by catalase, but not by superoxide dismutase, desferrioxamine, butylated hydroxyltoluene, and mannitol; whereas nonreducible crosslinking, like free radical lipid peroxidation, is inhibited by all of these agents except mannitol. Zinc(II) also inhibits lipid peroxidation, but stimulates disulfide bond formation to the virtual exclusion of all other crosslinking. Our results indicate that disulfide formation is dependent on H2O2, but not O2- or iron. However, O2-, H2O2, and iron are all required for lipid peroxidation and nondisulfide crosslinking, suggesting the intermediacy of OH generated via the iron-catalyzed Haber-Weiss reaction. The possible role of malonaldehyde (MDA, a by-product of lipid peroxidation) in the latter type of crosslinking was examined. Solubilized samples of xanthine/xanthine oxidase-treated membranes showed a strong visible fluorescence (emission maximum 450 nm; excitation 390 nm). This resembled the fluorescence of membranes treated with authentic MDA, which forms conjugated imine linkages between amino groups. Fluorescence scanning of SDS gels from MDA-treated membranes showed a strong signal coincident with crosslinked proteins and also one in the low molecular weight, nonprotein region, suggestive of aminolipid conjugates. Similar scanning on xanthine/xanthine oxidase-reacted membranes indicated that all fluorescence is associated with the lipid fraction. Thus, nonreducible protein crosslinks in this system do not appear to be of the MDA-derived, Schiff base type.
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PMID:Xanthine oxidase-catalyzed crosslinking of cell membrane proteins. 380 Mar 91

New evidence in support of zinc's role as a membrane antioxidant is presented. Human erythrocyte membranes in buffered saline underwent catalase- and superoxide dismutase-inhibitable lipid peroxidation when incubated with xanthine, xanthine oxidase, and Fe(III). Free radical mediated peroxidation was measured in terms of thiobarbituric acid reactivity and iodometric determination of lipid hydroperoxides. Whereas Ca(II) had relatively little effect on lipid peroxidation, Zn(II) strongly inhibited the reaction and suppressed peroxidation-dependent lysis of resealed membranes. Inhibition of lipid peroxidation was essentially complete in the presence of 0.1 mM Zn(II), a concentration equivalent to that of added Fe(III). By contrast, Zn(II) had no effect on rose bengal-photosensitized lipid peroxidation, a predominantly nonradical, singlet oxygen-driven process. Zinc(II) also interfered with xanthine/xanthine oxidase/iron-induced peroxidation of Triton X-100-dispersed membranes, but had no effect if EDTA was present. Trivial reasons for inhibition, for example, inactivation of xanthine oxidase or complex formation with O2-, were ruled out by showing that the rate of reduction of cytochrome c by xanthine/xanthine oxidase is not affected by Zn(II). We speculate that Zn(II) acts by interfering with the redox cycling of iron, possibly by competing with the latter for membrane binding sites.
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PMID:Inhibitory effect of zinc(II) on free radical lipid peroxidation in erythrocyte membranes. 384 4

The trace elements iron, copper, and zinc and the minerals calcium and magnesium have been found associated to human milk fat. After solubilization of milk fat globule membranes with detergent, the major part of these elements within the fat fraction were found in the more hydrophilic outer fat globule membrane: Fe 61%, Cu 73%, Zn 64%, Ca 67%, and Mg 71%. Most of the remainder was found in the more hydrophobic inner membrane, while only small amounts of the elements were associated with the core triglyceride fraction. Gel filtration chromatography on Sepharose CL-6B indicates the major iron- and zinc-binding proteins in the outer membrane are xanthine oxidase and alkaline phosphatase.
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PMID:Iron, copper, zinc, calcium, and magnesium in human milk fat. 669 23

Amounts of Copper/zinc containing superoxide dismutase have been found in human seminal plasma. Superoxide dismutase inhibits the lipid peroxidation in the xanthine oxidase system. In seminal plasma of spermatozoa with a good motility the superoxide dismutase activity is higher than in those with a low motility.
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PMID:Superoxide dismutase in human semen. 683 45

A procedure has been developed to distinguish between the two forms of eukaryotic superoxide dismutases using a common activity assay. Treatment of cellular fractions with 2% sodium dodecyl sulfate at 37 degrees C for 30 min selectively inactivates the mitochondrial, manganese-containing variant without affecting the cytosolic copper, zinc-superoxide dismutase. After removing excess sodium dodecyl sulfate by precipitation with potassium chloride, the supernate is assayed using the xanthine oxidase-cytochrome c method.
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PMID:A method for distinguishing Cu,Zn- and Mn-containing superoxide dismutases. 684 3

Degradation of deoxyribonucleic acid (DNA) by 1,10-phenanthroline has been shown to require Cu(II), a reducing agent, and O2. Other metal ions do not substitute for Cu(II), and degradation of DNA is inhibited by metal ions that can form stable complexes with 1,10-phenanthroline, such as Co(II), Cd(II), Ni(II), or Zn(II), as well as by chelators that can bind copper, such as triethyltetraamine, neocuproine, or ethylenediaminetetraacetic acid (EDTA). Neocuproine, a specific copper chelator, is more effective than EDTA in inhibiting the breakdown of DNA. The degradation of DNA shows a requirement for a reducing agent which can be satisfied by either ascorbate or a thiol. A free radical generating system, e.g., xanthine oxidase-hypoxanthine, can substitute for the reducing agent. DNA degradation, in the presence of either an organic reducing agent or xanthine oxidase-hypoxanthine, is inhibited by hydroxyl radical scavengers and by catalase, suggesting that hydroxyl radical is the reactive species in DNA degradation and that hydrogen peroxide is an intermediate in hydroxyl radical generation.
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PMID:Degradation of deoxyribonucleic acid by a 1,10-phenanthroline-copper complex: the role of hydroxyl radicals. 747 Apr 43

Trace elements play an important role in oxygen metabolism and therefore in the formation of free radicals. Whereas iron and copper are usually the main enhancers of free radical formation, other trace elements, such as zinc and selenium, protect against the harmful effects of these radicals. To investigate the different protective mechanisms of zinc on radical formation, we examined the effects of added zinc and copper on superoxide dismutase activity. We also studied the effects of copper and iron on xanthine oxidase activity and on the Haber-Weiss cycle (iron, superoxide, and hydrogen peroxide), which generates hydroxyl radicals in vitro. The hypoxanthine/xanthine oxidase radical generating system contained a variety of different physiological ligands for binding the iron. This study confirmed the inhibitory effect of copper on xanthine oxidase activity. Moreover, it demonstrated that zinc inhibited hydroxyl radical formation when this formation was catalyzed by a citrate-iron complex in the hypoxanthine/xanthine oxidase reaction. Finally, human blood plasma inhibited citrate-iron-dependent hydroxyl radical formation under the same conditions. Although trace elements seemed responsible for this antioxidant activity of plasma, it is likely that zinc played no role as a plasma antioxidant. Indeed, calcium appeared to be responsible for most of this effect under our experimental conditions.
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PMID:Effect of zinc on superoxide-dependent hydroxyl radical production in vitro. 750 44

We determined that mitochondrial respiration reduced cytosolic oxidant stress in vivo and scavenged extramitochondrial superoxide anion (O2-.) in vitro. First, Saccharomyces cerevisiae deficient in both the cytosolic antioxidant cupro-zinc superoxide dismutase (Cu,Zn-SOD) and electron transport (Rho0 state) grew poorly (P < 0.05) in 21% O2 compared with parent yeast and yeast deficient only in electron transport or Cu,Zn-SOD, whereas anaerobic growth was the same (P > 0.05) in all yeast. Second, isolated yeast and mammalian mitochondria scavenged extramitochondrial O2-. generated by xanthine/xanthine oxidase. Yeast mitochondria scavenged 42% more (P < 0.05) extramitochondrial O2-. during pyruvate/malate-induced respiration than in the resting state. Addition of either antimycin (respiratory chain inhibitor) or FCCP (respiratory chain uncoupler) prevented increased O2-. scavenging. Mitochondria isolated from yeast deficient in the mitochondrial manganous superoxide dismutase (Mn-SOD) increased (P < 0.05) O2-. scavenging 56% during respiration. This apparent SOD activity, expressed in units of SOD activity per milligram of mitochondrial protein, was the same (9 +/- 0.6 vs. 10 +/- 1.0; P = 0.43) as the O2-. scavenging of mitochondria with Mn-SOD, suggesting that respiration-dependent mitochondrial O2-. scavenging was nonenzymatic. Finally, isolated rat liver and lung mitochondria also increased (P < 0.05) O2-. scavenging during respiration. We speculate that respiring mitochondria, via the protonmotive pump, present a polarized, proton-rich surface that enhances nonenzymatic dismutation of extramitochondrial O2-. and that this is a previously unrecognized function of mitochondrial respiration with potential physiological ramifications.
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PMID:Mitochondrial respiration scavenges extramitochondrial superoxide anion via a nonenzymatic mechanism. 763 49

In purified system zinc has been shown to have an antioxidant role. Its effects on the resistance of cultured cells towards oxidative stress in vitro were examined. Diploid human skin fibroblasts were grown for 21 d in culture media (RPMI 1640 containing 15% fetal calf serum) added with different zinc (Zn) concentrations (100, 125, and 150 microM as Zinc chlorur ZnCl2). In comparison, cell controls were grown in standard culture media (6.5 microM Zn). The intracellular zinc levels of treated fibroblasts increased from 3- to 7-fold (2330 +/- 120 ng/mg protein in 150-microM Zn-treated cells versus 331 +/- 21 ng/mg protein in control cells). The intracellular copper increased 3- fold whereas the iron content slightly but not significantly decreased. The index of basal lipid peroxidation measured as thiobarbituric acid reactants (TBARs) of zinc-supplemented cells was lower than that of non zinc supplemented controls (0.89 mumol/g protein in 150 microM Zn-treated cells versus 1.59 mumol/g protein in controls). At these high doses of zinc, fibroblasts expressed lower antioxidant metalloenzymes activities. Diminished TBARs in Zn treated cells tends to support that Zn acts protectively against free radical mediated damage. However when the cells were challenged with extracellular oxidant stresses mediated by hypoxanthine/xanthine oxidase or hydrogen peroxide (H2O2), an increased toxicity in Zn-supplemented cells was observed. When we applied an intracellular oxidative stress as UV-B or UV-A radiation, Zn-treated fibroblasts were more resistant than cells grown in normal medium. If Zn has shown antioxidant effect in some in vitro or in vivo systems our observations clearly demonstrate that this role is not mediated by antioxidant metalloenzymes.
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PMID:Effect of zinc supplementation on resistance of cultured human skin fibroblasts toward oxidant stress. 768 32

The effects of Zn, Mg, Cr, Cu, and Mn aspartates, their commercial formulation Inzolen, and the individual commercial medicine Unizinc, on oxygen radical production by enzymes [xanthine oxidase, horseradish peroxidase, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase] and phagocytic cells (human blood leukocytes) have been studied. The formation of oxygen radicals was measured by luminol- and lucigenin-amplified chemiluminescence and by the reduction of cytochrome c. All these compounds (excluding Cr aspartate) turn out to be inhibitors of oxygen radical formation in the systems studied (excluding horseradish peroxidase). Their inhibitory activities were a consequence of both the scavenging of free radicals and the inhibition of xanthine oxidase and NADPH oxidase activities. As expected, the most active free-radical scavengers were transition metal Cu and Mn aspartates, which mimicked the activities of copper-zinc and manganese dismutases. However, surprisingly non-transition metal Zn and Mg aspartates were also able to scavenge oxygen radicals. It was suggested that the scavenging activities of Zn and Mg aspartates may be explained by affecting the rate of spontaneous dismutation of the superoxide ion. In addition, it was found that Zn aspartate is an efficient inhibitor of the formation of the most reactive hydroxyl radicals. These antioxidant properties of Zn aspartate make it important in medicine for the prevention and treatment of free radical pathologies.
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PMID:Study of antioxidant properties of metal aspartates. 774 Dec 42


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