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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species (ROS) generated from xanthine oxidase (XO) play an important role in ischemia-induced injury. We hypothesize that XO and xanthine dehydrogenase (XDH) are released into the circulation with ischemia reperfusion to the human liver and intestine. Blood was drawn from a patient, before and at intervals after an aortic cross-clamp procedure. Plasma was incubated in the presence of xanthine, with NAD+ (for XD +XO) and without NAD+ (for XO). The amount of urate formed was quantified using a high-performance liquid chromatograph (HPLC). The calculated XDH+XO and XO activity increased from 1.88 and 1.66 microU/mg protein, respectively, before the cross clamp to 3.77 and 3.11 microU/mg, respectively, 7 minutes after reperfusion to the superior mesenteric, celiac, and right renal artery beds. The release of a significant biological source of ROS may explain the damage to lung or heart observed after ischemia to the human liver and intestine.
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PMID:Circulating xanthine oxidase in human ischemia reperfusion. 771 6

Oxygen-derived free radicals (ODFR) appear to be involved in the pathogenesis of arthritic disorders. In order to gain new insight on their role in the phenomenon and as a basis for a therapeutic approach, the effect of ODFR (produced by the xanthine oxidase-hypoxantine system) on hyaluronic acid, on two HA ester derivatives, and on pig articular chondrocytes was investigated. High M(r) HA (1.1 x 10(6)) and low M(r) HA (16 x 10(4)) were depolymerized by ODFR but the methyl and hydrocortisone esters of HA (HYAFF 2P50 and HYC13) turned out to be nearly unaffected. When articular chondrocytes were treated with ODFR, a rapid nucleoside triphosphate (NTP) depletion, a transient appearance of pyrophosphate (PPi), and an increase of phosphomonoester and diphosphodiester concentrations have been observed. The NTP depletion and the DPDE increase are related to the concentration of free radicals. Glyceraldehyde-3-phosphate accumulation during ODFR treatment suggests that ATP depletion can occur as a consequence of the blockage of glycolysis at the level of glyceraldehyde-3-P dehydrogenase. The hypothesis is presented that PPi can be produced from the pathway of the FAD-NAD (DPDE) biosynthesis and then either hydrolyzed by endogenous pyrophosphatases or precipitated in the form of insoluble calcium salts. Long-term treatment (16 h) with ODFR causes a loss of chondrocyte membrane integrity which can be revealed both by an increased free LDH activity and by the characteristic signal of free phospholipids in the 31P-NMR spectra. While high M(r) HA shows a significant protective activity for chondrocytes against ODFR action, low M(r) HA and ester derivatives do not. It is suggested that the therapeutic activity of HA ester derivatives can be ascribed to their in vivo hydrolysis products.
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PMID:Oxygen-derived free radical (ODFR) action on hyaluronan (HA), on two HA ester derivatives, and on the metabolism of articular chondrocytes. 773 82

When cultures of pancreatic islet cells are exposed to the nitric oxide donor sodium nitroprusside, to enzymatically generated reactive oxygen intermediates or to streptozotocin cell lysis occurs after 4-12 h. We report here that a heat shock at 43 degrees C for 90 min reduces cell lysis from nitric oxide (0.45 mM sodium nitroprusside) by 70%, from reactive oxygen intermediates (12 mU xanthine oxidase and 0.05 mM hypoxanthine) by 80% and from streptozotocin (1.5 mM) by 90%. Heat shock induced resistance was observed immediately after termination of the 90 min culture at 43 degrees C and correlated with enhanced expression of hsp70. The occurrence of DNA strand breaks, a major early consequence of nitric oxide, reactive oxygen intermediates, or streptozotocin action, was not suppressed by heat shock treatment. However, the depletion of NAD+, the major cause of radical induced islet cell death, was suppressed after heat shock (P < 0.01). We conclude that pancreatic islet cells can rapidly activate defence mechanisms against nitric oxide, reactive oxygen intermediates and streptozotocin by culture at 43 degrees C. Islet cell survival is due to the prevention of lethal NAD+ depletion during DNA repair, probably by slowing down poly(ADP-ribose)polymerase activation.
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PMID:Heat shock induces resistance in rat pancreatic islet cells against nitric oxide, oxygen radicals and streptozotocin toxicity in vitro. 776 24

Although mammalian xanthine oxidase exists originally as a dehydrogenase form in freshly prepared samples, it is converted to an oxidase form during purification, either irreversibly by proteolysis or reversibly by sulfhydryl oxidation of the protein molecule. However, avoiding proteolysis the mammalian enzyme can be purified as an interconvertible form and thus can be used to compare directly the properties of xanthine dehydrogenase and the oxidase derived from the same enzyme molecule. The cDNAs encoding the enzyme have been cloned from several sources, and structural information is becoming available. The most significant difference between the two forms is the protein conformation around FAD, which changes the redox potential of the flavin and the reactivity of FAD with the electron acceptors, NAD and molecular oxygen. The flavin semiquinone is thermodynamically stable in xanthine dehydrogenase, but is unstable in xanthine oxidase. Detailed analyses by stopped-flow techniques suggest that the flavin semiquinone reacts with oxygen to form superoxide anion while the fully reduced flavin reacts to form hydrogen peroxide. Although xanthine dehydrogenase can produce greater amounts of superoxide anion than xanthine oxidase during xanthine-oxygen turnover, it seems to be physiologically insignificant because NAD inhibits almost completely the formation of superoxide anion. Although the involvement of this enzyme in reperfusion injury has been proposed, this seems to be more complex than originally envisaged and still remains to be established.
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PMID:The conversion of xanthine dehydrogenase to xanthine oxidase and the role of the enzyme in reperfusion injury. 779 66

Despite extensive studies on streptozotocin, alloxan and nitric oxide toxicity in pancreatic islets the mechanism of oxygen radical induced islet cell death has not been determined. The present study shows at the level of single cells that following exposure to oxygen radicals generated from xanthine oxidase DNA strand breaks occur in cell nuclei within 5-60 min and precede cell death by several hours. Similar kinetics were seen when treating islet cells with the alkylating agent streptozotocin. Immunofluorescence studies demonstrated the endogenous formation of ADP-ribose polymers in nearly all islet cell nuclei within minutes of treatment with xanthine oxidase, indicating activation of the enzyme poly(ADP-ribose) polymerase (PARP). Concomitantly, cellular NAD+ depletion was noted. Nicotinamide largely prevented NAD+ depletion and in parallel resulted in islet cell survival. These findings identify islet cell nuclear DNA as a primary target of oxygen radical toxicity and suggest related pathways of oxygen radical, nitric oxide and streptozotocin toxicity.
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PMID:Analysis of oxygen radical toxicity in pancreatic islets at the single cell level. 784 Sep 1

Since a single nephron is a functional unit of the kidney, individual microdissected segments from the nephron would be ideal tissue samples for investigations on renal pharmacology. Several micromethods have enabled researchers to analyze the biochemical and pharmacological characteristics of these nephron segments. Miniaturized cuvettes containing microliter volumes of samples can be applied for general procedures of photometry like Lowry's protein determination. Fluorometry becomes a more sensitive method when enzymatic cycling systems of NAD/NADH or NADP/NADPH are combined, which have been used for assays of enzyme activities or substrate contents in minute biological samples having tissue proteins less than 1 microgram. The microchemiluminescence procedure has been successfully utilized for cellular ATP content or oxygen radical generation. Radioimmunoassay can be used to determine endogenous components such as cyclic nucleotides, eicosanoids, etc. Continuous gradient polyacrylamide microgels prepared in 5- to 10-microliters capillaries have made it possible to quantify the intranephron distribution of cytochrome P-450, xanthine oxidase and superoxide dismutase. As an example of the modern techniques, microscopic fluorometry using Fura-2AM has been established to identify agonist-induced cytosolic free calcium transients.
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PMID:[Micromethods for the determination of metabolic characteristics in individual nephron segments]. 790 40

Xanthine dehydrogenase (XDH) is an important precursor to the oxygen radical producing enzyme xanthine oxidase (XO). We found that the apparent activity of rabbit myocardial XDH increased from 2 +/- 1 to 50 +/- 3 microU/g (P < 0.05) following extraction of tissue homogenate with butanol. Further studies suggested that the basis for this observation was a high molecular weight compound which consumes the XDH cofactor, NAD+. Addition of myocardial homogenate to exogenous NAD+ resulted in depletion of NAD+ and concomitant formation of an additional compound (peak A). Both NAD+ consumption and peak A formation were abrogated by prior extraction of homogenate with butanol. Separation of myocardial homogenate by Sephadex chromatography revealed a high molecular weight compound which suppressed activity of purified milk XDH but not xanthine oxidase (XO). This activity co-eluted with the ability of myocardial homogenate to consume added NAD+ and form peak A. The NAD(+)-consuming activity was heat and acid-labile. In addition, nicotinamide was both a product and an inhibitor of the NADase activity, consistent with the existence of a previously described myocardial glycohydrolase. Extraction of tissue with butanol may be necessary to detect low levels of XDH activity in vitro.
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PMID:Suppression of rabbit myocardial xanthine dehydrogenase activity by an endogenous compound. 800 74

In this study we examined the intracellular sources of superoxide anion (O2-.) in cultured bovine coronary endothelium, employing lucigenin (250 microM)-elicited chemiluminescence (CL). In the homogenate from these cells, 100 microM NADPH increased O2-. by 81% from 8.9 +/- 1.5 to 16.0 +/- 1.5 x 10(5) cpm/mg protein (P < 0.01, n = 8). In the presence of 100 microM NADH, however, CL increased by 458% from 8.9 +/- 1.6 to 49.6 +/- 12.0 x 10(5) cpm/mg protein (P < 0.01, n = 8). Scavengers of O2-., superoxide dismutase (100 micrograms/ml), or 4,5-dihydroxy-1,3-benzenedisulfonic acid disodium salt (Tiron, 10 mM) inhibited NADH-mediated CL by 70 and 83%, respectively. Neither hypoxanthine (100 microM) nor antimycin (10 microM)+succinate (5 mM) had any significant effect on basal CL levels, thereby excluding xanthine oxidase and mitochondria, respectively, as a detectable sources of O2-. generation. The presence of NAD+ (100 microM) and lactate (1 mM) increased CL by 88% (n = 8, P < 0.01). In the intact cells, basal production of CL was increased by 205% (P < 0.01) by 5 mM lactate, but not by 5 mM pyruvate, and CL was inhibited by 10 mM Tiron, suggesting the reduction of cytosolic NAD by lactate dehydrogenase stimulates O2-. production. Diphenyliodonium at 1 and 10 microM inhibited both NADH-mediated CL in homogenate and lactate-mediated CL in intact endothelium by 50 and 33%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium. 802 19

These experiments are a continuation of our work describing the effect of H2O2 and O2- on DNA strand breaks, NAD pools and poly(ADP-ribose) synthesis in C3H10T1/2 cells (Lautier et al. (1990) Biochem. Cell Biol. 68, 602-608). The current experiments were carried out firstly to evaluate the polymer synthesis in C3H10T1/2 cells exposed to benzamide, oxygen radicals and hyperthermia. Secondly, using four different protocols for the time of addition and removal of benzamide, the lowest benzamide levels shown to inhibit polymer synthesis were used to study the effect on plating efficiency and colony-forming ability of cells exposed to H2O2 and O2(-). Plating efficiency and colony-forming ability were affected by the active oxygen-species-generating system xanthine-xanthine oxidase and 100 microM benzamide. With higher levels of benzamide, this effect disappeared, and 0.5 to 1 mM benzamide were actually protective against the effects of xanthine-xanthine oxidase, suggesting the involvement of other processes in addition to poly(ADP-ribosyl)ation in response to oxygen radical damage.
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PMID:The role of poly(ADP-ribose) metabolism in response to active oxygen cytotoxicity. 816 42

We isolated cDNAs encoding xanthine dehydrogenase (XD; xanthine:NAD+ oxidoreductase, EC 1.1.1.204) from a human liver cDNA library. The complete nucleotide sequence of human XD was determined; the deduced amino acid sequence encoded a protein of 1336 amino acid residues of M(r) 147,782. Human XD possessed many of the signature sequences typical of XDs from flies and rodents, including an unusual cysteine distribution, a potential 2Fe/2S binding site, and a putative molybdopterin cofactor binding domain. Analysis of potential NAD binding sites suggested a simple hypothesis for the conversion of human XD into the oxygen metabolite forming xanthine oxidase (XO; xanthine:oxygen oxidoreductase, EC 1.1.3.22). Using a human XD complementary RNA hybridization probe, we found a 5100-base RNA in human liver by RNA blot-hybridization analysis. This RNA exhibited tissue-specific distribution that may be pertinent to XD- and XO-mediated oxygen radical injury in ischemia/reperfusion and inflammation. A second 4500-base RNA was detected in some tissues and may arise through differential transcription termination.
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PMID:cDNA cloning, characterization, and tissue-specific expression of human xanthine dehydrogenase/xanthine oxidase. 824 61


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