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)

Xanthine dehydrogenase (XDH, EC 1.1.1.204) oxidizes a variety of purines, pterins, and other heterogenic nitrogen compounds, serving as a rate-limiting enzyme in nucleic acid degradation. The genetic defect of XDH results in hereditary xanthinuria and other disorders in purine metabolism. Based on the cloning and sequencing results of human XDH cDNA in our laboratory, we studied the localization and sublocalization of the XDH gene. A Version 3.0 human-hamster somatic cell hybrid PCRable DNA panel and specific PCR primers derived from human XDH cDNA for amplification were used to assign the XDH gene to human chromosome 2. The fidelity of the PCR product was confirmed by nucleotide sequencing the PCR product. The assignment of the XDH gene to chromosome 2 at band p22 was established by fluorescence in situ hybridization on human metaphase chromosomes using a clone from a pWE 15 cosmid library containing the XDH gene. The results should be useful for further studies of the molecular basis for hereditary xanthinuria and other genetic disorders related to abnormal XDH activity.
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PMID:Assignment of human xanthine dehydrogenase gene to chromosome 2p22. 782 92

It is currently believed that reactive oxygen species are produced in the heart post-ischemia reperfusion, causing pathophysiological disorders. Studies reported in the literature dealing with this subject have generated contradictory findings. The aim of this study was to assess the catalytic activity of the superoxide anion-producing enzyme xanthine oxidase, and the level of lipid peroxides in isolated rat heart muscle undergoing ischemia of varying duration and severity followed by reperfusion. Three levels of ischemia were investigated: total, and partial at either 0.10 or 0.35 ml/min (residual flow rate). Three different periods of ischemia were examined in each case. After each period of ischemia, followed by 10 min of reperfusion, the heart was frozen in liquid nitrogen. Xanthine oxidase activity and lipid peroxide levels were assayed in the cardiac homogenate and in the centrifuged supernatant, respectively. In the different experimental protocols studied here, both cardiac xanthine oxidase and lipid peroxide levels remained statistically unchanged compared to the continuously perfused control hearts. Moreover, in a recent study (Boucher et al., FEBS Lett. 203, 261-264, 1992), we were unable to detect reactive oxygen species in perfusate upon reperfusion of ischemic rat hearts. These results suggest that changes in xanthine oxidase activity during myocardial ischemia-reperfusion, and lipid peroxidation, as assessed by measuring thiobarbituric acid reactants and lipid hydroperoxides, are not predominant phenomena in ischemia-reperfusion-induced injury, at least in the experimental model used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Xanthine oxidase activity and lipid peroxide content following different types of ischemia in the isolated rat heart. 794 21

Active sodium (Na+) transport by alveolar type II (ATII) cells plays an important role in limiting the volume of alveolar fluid. Reactive oxygen and nitrogen species, released in the epithelial lining fluid by activated inflammatory cells or present in inspired gases, may damage Na+ transporters and decrease fluid reabsorption. To test this hypothesis we exposed ATII cells to xanthine and xanthine oxidase (1 or 10 mU/ml), or to boluses of peroxynitrite (0.1-1 mM final concentration) for 15 min and measured 1) cellular oxygen consumption (VO2); 2) amiloride-inhibitable 22Na+ uptake, as an index of Na+ movement through apically located Na+ channels; and 3) ouabain-sensitive 86Rb+ uptake, as an index of the activity of the basolaterally located Na(+)-K(+)-ATPase. After exposure of ATII cells to 0.5 or 1 mM peroxynitrite, amiloride-inhibitable 22Na+ uptake decreased to 68 +/- 7 and 56 +/- 11 of their control values, respectively (mean +/- SE; n > or = 6). Exposure to 0.5 mM peroxynitrite decreased ATII cell VO2 from 76 +/- 6 to 25 +/- 5 microM.h-1 x 10(6) cells-1 (mean +/- SE; n = 5). Cell viability and ouabain-sensitive 86Rb+ uptake remained at control levels for either peroxynitrite concentration. Exposure of ATII cells to 10 mU/ml xanthine oxidase decreased their VO2 from 94 +/- 8 to 63 +/- 6 (mean +/- SE; n = 5), but did not alter amiloride-inhibitable 22Na+ uptake. These findings indicate that physiological concentrations of peroxynitrite, but not of reactive oxygen species, decrease ATII cell Na+ transport by damaging apically located amiloride-sensitive Na+ channels.
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PMID:Peroxynitrite inhibition of oxygen consumption and sodium transport in alveolar type II cells. 802 51

Recent findings have suggested that nitric oxide (NO) reacts with superoxide anion (O2-) to form a potential oxidant, peroxynitrite anion, which then decays to hydroxyl radical and nitrogen dioxide. In order to ascertain this hypothesis in human polymorphonuclear leukocytes (PMNs) which release both NO and O2-, we studied oxidation of L-cysteine (CYS) and bovine serum albumin (BSA) by PMNs and cell-free O2(-)-generating system of hypoxanthine (HX)-xanthine oxidase (XO) reaction. Oxidation of CYS by HX-XO was equally inhibited by superoxide dismutase (SOD) and catalase (CAT), and that of BSA by HX-XO was inhibited weakly by SOD and strongly by CAT. PMNs stimulated with phorbol 12-myristate 13-acetate increased the oxidation rates of CYS and BSA, and they were inhibited by SOD and CAT almost in a similar way to those by HX-XO. The NO synthase inhibitor, NG-monomethyl-L-arginine (NMMA), was confirmed to have an inhibitory effect on the inhibition of platelet aggregation by PMNs, and L-arginine (ARG) reversed this effect. However, pretreatment of PMNs with either of NMMA, or ARG, or both did not change the oxidation rates of CYS and BSA. We could not confirm the hypothesis at least in human PMNs that interaction of NO with O2- forms powerful oxidants to sulfhydryls of CYS and BSA. These results suggest that oxidation of sulfhydryls of CYS and BSA by PMNs is primarily dependent on reactive oxygen species, and is not modified by NO production.
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PMID:Nitric oxide does not contribute to superoxide-mediated sulfhydryl oxidation in human polymorphonuclear leukocytes. 803 64

Xanthine dehydrogenase (XDH, EC 1.1.1.204) is a molybdenum iron-sulphur flavin hydroxylase which oxidizes a variety of purines, pterins and other heterogenic nitrogen compounds, serving as a rate-limiting enzyme in nucleic acid degradation. In this work, we have isolated and sequenced cDNA clones of human liver XDH. The obtained cDNA covers 4577 bases of human liver XDH mRNA with a 63 bp 5'-end untranslated region and a 515 bp 3'-end untranslated region. A termination codon TGA and a polyadenylation signal AATAAA were identified. An open reading frame encodes 1333 amino acid residues. The assignment of the N-terminal was confirmed by directly sequencing that region of purified human milk XDH. Northern blot analysis shows that the human XDH gene is widely expressed in human tissues.
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PMID:Molecular cloning, tissue expression of human xanthine dehydrogenase. 757 23

The pulsed EPR technique of electron spin echo envelope modulation (ESEEM) has been utilized to examined both the 'very rapid' and 'desulfo inhibited' Mo(V) signals of xanthine oxidase in order to probe for magnetic interactions with nitrogen, phosphorus and hydrogen nuclei. No 14N modulation is observed in the 'desulfo inhibited' EPR signal, indicating that histidine is unlikely to be a ligand to molybdenum. Strong 14N modulation is observed in the 'very rapid' EPR signal formed with 2-hydroxy-6-methylpurine substrate bound to molybdenum. We interpret this modulation as arising from nitrogens of the bound purine substrate. This interpretation is consistent with the present evidence indicating that the purine ring present in the species giving rise to the 'very rapid' EPR signal is coordinated to the molybdenum center through the catalytically introduced hydroxyl group. No modulation is observed from non-exchangeable deuterons in experiments performed with deuterated 2-hydroxy-6-methylpurine. Given the signal-to-noise level of the spectra, the lack of modulation indicates that each of the substrate methyl group deuterons is greater than 4.9 A from the Mo(V). The deuteron removed from the C8 position in the binding of the substrate is also exchanged to a site or sites greater than 4.9 A from the Mo(V) in the time-course of sample preparation. Moderately deep deuteron modulation arises from exchangeable sites. A large portion of this modulation can be accounted for by the exchangeable N7 deuteron of the 2-hydroxy-6-methylpurine substrate, which we estimate to be approximately 3.2 A from the molybdenum. Additional exchangeable deuterons on the protein or within the buffer must be present within 5 A of the molybdenum to account for the remaining modulation. No modulation from weakly-coupled 31P nuclei is observed in either the 'desulfo inhibited' or 'very rapid' EPR signal.
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PMID:Electron spin echo envelope modulation spectroscopy of the molybdenum center of xanthine oxidase. 818 Feb 33

We previously isolated the strain Z-54 (Serratia marcescens O5:H1) which produces a reddish-violet pigment. The structure of this pigment was confirmed to be that of a peptide complex containing Fe2+ and L-2(2-pyridyl)-1-pyrroline-5-carboxylic acid (pyrimine), as a chromophore. We measured the superoxide dismutase mimetic activities for the pyrimine-metal complexes by xanthine oxidase/nitroblue tetrazolium and cytochrome c methods and found that the pyrimine-Cu2+ (2:1) complex shows the highest activity yet reported (IC50 = 0.11 microM) among the complexes tested. Pyrimine-Cu+, -Fe2+ and -Mn2+ complexes also gave relatively high SOD mimetic activities. ESR spectra observed for pyrimine-Cu2+ (4:1) showed the structure of the Cu(2+)-complex to be tetrahedral and coordinated with four nitrogen atoms. These results support the idea that the pyrimine-metal complexes might be potent SOD mimics.
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PMID:Superoxide dismutase mimetic activities of metal complexes of L-2(2-pyridyl)-1-pyrroline-5-carboxylic acid (pyrimine). 826 87

Aortic aneurysm repair produces inflammatory mediators, neutrophil activation, and remote organ injury. Reperfusion plasma from these patients produces microvascular injury in an ex vivo chemotactic model. This study investigates the mechanism of this injury. Vena caval blood was obtained before and 15 minutes after aortic clamp removal (n = 16) or at laparotomy (n = 10). Plasma or saline solution was introduced into unit dose chambers fixed atop dermabrasions on the back of depilated anesthetized rabbits. Animals were treated with intravenous saline solution (n = 4); made neutropenic with nitrogen mustard (n = 4); pretreated with the xanthine oxidase inhibitor allopurinol (n = 4); or cotreated intravenously with the free radical scavengers superoxide dismutase (SOD) and catalase (n = 4). Three hours later neutrophil counts (polymorphonuclear cells [PMN]/mm3) and activity (free radical production by flow cytometry), protein leakage, and inflammatory mediators (thromboxane [TX] and leukotriene B4 [LTB4]) were measured. In contrast to control plasma in untreated rabbits, reperfusion plasma produced TX and LTB4 generation (1090 +/- 105 and 794 +/- 91 pg/ml, respectively, p < 0.01), PMN accumulation (1636 +/- 210/mm3, p < 0.01) and activation (276 +/- 31 mean fluorescent units), and microvascular permeability (554 +/- 90 micrograms/ml, p < 0.01). Neutropenia (3 +/- 1 PMN/mm3) and cotreatment with SOD and catalase abolished these responses, whereas pretreatment with allopurinol did not. Human reperfusion plasma contains a soluble factor that stimulates free radical generation by rabbit neutrophils to produce a microvascular injury characterized by de novo TX production, neutrophil accumulation and activation, and increased microvascular permeability to protein.
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PMID:Reperfusion plasma contains a neutrophil activator. 839 Aug 48

Peroxynitrite is the product of the reaction between nitric oxide and superoxide. It is an oxidant which can also decompose to form the hydroxyl radical and nitrogen dioxide. In this report we show that a powerful oxidant with reactivity similar to that of the hydroxyl radical is formed from the generation of superoxide from xanthine oxidase and nitric oxide from S-nitroso-n-acetylpenicillamine (SNAP). Simultaneous generation of these two radicals by either xanthine oxidase/SNAP or the sydnonimine SIN-1 in the presence of low-density lipoprotein (LDL) results in the depletion of alpha-tocopherol and formation of its oxidised product alpha-tocopheroquinone. The mechanism of oxidation required both the formation of nitric oxide and superoxide. In contrast to the promotion of LDL oxidation by transition metals the oxidation of LDL by SIN-1 was not sensitive to the addition of exogenous lipid hydroperoxide.
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PMID:The oxidation of alpha-tocopherol in human low-density lipoprotein by the simultaneous generation of superoxide and nitric oxide. 839 94

Initial ferricytochrome c (Cyt(III)c) reduction rates occurring in aerobic or anaerobic solutions containing either 3-nitrobenzothiazolo[3,2-a]-(NBQCl), 1-ethyl-3-nitrobenzimidazolo[3,2-a]-(ENBIQCl), 7-ethylbenzimidazolo[3,2-a]quinolinium chloride (EHBIQCL), or nitrofurantoin (NFT) and xanthine/xanthine oxidase were measured. Maximum rates in nitrogen-saturated solutions follow the order NFT > NBQCL > ENBIQCL > EHBIQCL. These rates correlate linearly with the half-wave reduction potentials (E1/2) of these compounds. With the exception of EHBIQCl, smaller rates of Cyt(III)c reduction were obtained in air-saturated than in nitrogen-saturated solutions at the quinolinium salt concentrations used. Larger concentrations of superoxide dismutase (SOD) are needed for 50% inhibition of the Cyt(III)c reduction reaction for heterocyclic compounds with larger E1/2 values. Thus, measurement of the portion of the Cyt(III)c reduction rate under air that is inhibited by SOD does not account solely for the production of superoxide. These observations suggest that NBQCL, ENBIQCl, and less probably EHBIQCl may interfere with mitochondrial energy metabolism or induce DNA damage through reduced intermediates.
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PMID:Reductive activation of benzazolo[3,2-a]-quinolinium chlorides. 839 53


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