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)

Both xanthine dehydrogenase (XD) and xanthine oxidase (XO) catalyze the conversion of hypoxanthine to xanthine, and xanthine to uric acid. Topical application of a promoting dose of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of female SENCAR mice resulted in a 3.0-3.5-fold elevation of epidermal XO specific activity. Epidermal XO specific activity was maximally elevated 48-96 h after TPA treatment, and required 11 days to return to control levels. Although TPA increased the XO/(XD + XO) ratio from 0.45 to 0.7, the conversion of preexisting XD to XO could not solely account for the TPA-dependent elevation in XO specific activity since control XD plus XO activity was less than just the XO activity in TPA-treated epidermis. Topical application of cycloheximide simultaneously with, or 12 h after, TPA treatment inhibited the TPA-dependent increases in the XO/(XD + XO) ratio and XO specific activities. Collectively, these results suggest that the increased XO activity detected following TPA treatment is the consequence of TPA-induced XD synthesis, and a conversion of existing and newly synthesized XD to XO. In addition, the in vivo promoting activities of analogues of TPA could be correlated with their abilities to elevate XO activity (TPA greater than phorbol-12,13-dibenzoate much greater than 4-O-methyl-TPA = phorbol).
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PMID:12-O-tetradecanoylphorbol-13-acetate-dependent induction of xanthine dehydrogenase and conversion to xanthine oxidase in murine epidermis. 346 21

The antioxidant properties of alpha-tocopherol and alpha-tocopheryl acetate in lung tissue were quantitated in vitro by measurement of thiobarbituric acid (TBA) reactants, pentane production and lipid peroxides following either an iron/ascorbate or a xanthine/xanthine oxidase oxidant stress. Lung homogenates were obtained from newborn rabbits treated intravenously with either 10 or 100 mg/kg of either alpha-tocopherol or alpha-tocopheryl acetate. The animals were killed 5 min after dosing to minimize the conversion of alpha-tocopheryl acetate to alpha-tocopherol. Lung homogenates from animals treated with alpha-tocopherol had decreased concentrations of TBA reactants and pentane production after incubation with either oxidant stress compared to lung homogenate from animals treated with alpha-tocopheryl acetate or vehicle alone. Lipid peroxide concentrations were no different in homogenates from alpha-tocopherol or alpha-tocopheryl acetate treated animals. Correlations between antioxidant activity and tissue concentrations of alpha-tocopherol indicate 50% inhibition is achieved with 30-100 micrograms/g lung tissue. In vitro addition of alpha-tocopherol required concentrations between 100 and 200 micrograms/g to reduce lipid peroxidation by 50%.
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PMID:Comparison of the antioxidant properties of alpha-tocopherol and alpha-tocopheryl acetate in newborn rabbit lung. 360 49

Topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to SENCAR mouse skin results within 48 h in a 3-fold elevation of xanthine oxidase (XO) activity, an enzyme capable of generating the reactive oxygen species superoxide and hydrogen peroxide. The antiinflammatory steroid fluocinolone acetonide, an inhibitor of TPA-induced hyperplasia, as well as the multiple stages of tumor promotion as defined in SENCAR mice (Stages I and II), inhibited the TPA-dependent elevation of epidermal XO activity. Neither tosylphenylalanyl chloromethyl ketone nor retinoic acid, inhibitors of promotion Stages I and II, respectively, had significant effects on TPA-induced hyperplasia or elevated XO activity. The nonpromoting but hyperplasiogenic agents ethyl phenylpropiolate and acetic acid significantly elevated XO activity within 48 h of topical application. The non-phorbol ester tumor promoter benzoyl peroxide also elevated XO activity consistent with the degree of induced hyperplasia. Multiple treatments with TPA or ethyl phenylpropiolate resulted in a sustained elevation of XO activity which peaked at five treatments and then declined. Sustained inhibition of XO activity by p.o. administration of allopurinol did not inhibit the TPA-induced hyperplasia as determined histologically. These results suggest that the TPA-dependent elevation of epidermal XO activity is associated with the hyperplasia induced by the agent, and is a consequence of the hyperplasia rather than the cause of it.
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PMID:Murine epidermal xanthine oxidase activity: correlation with degree of hyperplasia induced by tumor promoters. 367 84

Isoelectric focusing (IEF) and cellulose acetate electrophoresis were used to examine the multiplicity and distribution of aldehyde dehydrogenases (ALDHs), aldehyde oxidase (AOX) and xanthine oxidase (XOX) from tissues of olive and yellow baboons. Five ALDHs were resolved and distinguished on the basis of their differential tissue and subcellular distribution or substrate specificity. Some ALDHs exhibited multiple activity zones. Baboon liver ALDHs were differentially distributed in cytosol (ALDHs II, III and V) and large granular (mitochondrial) fractions (ALDHs I and IV). The major liver ALDHs (I and II) were also broadly distributed in other tissues, as was the major stomach enzyme (ALDH-III). Three brain ALDHs were resolved, which were also differentially distributed between large granular (mitochondrial) (ALDHs I and IV) and cytosolic (ALDH-III) fractions. Electrophoretic variability between individuals was observed for the major liver mitochondrial isozyme (ALDH-I), the major stomach isozyme (ALDH-III) and the minor liver isozymes (ALDHs IV and V). Single forms of AOX and XOX were found in baboon tissue extracts, with the highest activities in liver (AOX) and intestine extracts (XOX). Both oxidases were predominantly localized in the liver soluble fraction.
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PMID:Aldehyde dehydrogenases, aldehyde oxidase and xanthine oxidase from baboon tissues: phenotypic variability and subcellular distribution in liver and brain. 375 5

To develop a sensitive in vitro assay for detecting endothelial cell damage, we radiolabeled endothelial cell monolayers with tracer amounts of 2-deoxy-D-[1-3H]-glucose (3HDOG). We damaged identical cohorts of endothelial cells radiolabeled with 3HDOG or chromium 51 by exposing monolayers to toxic oxygen radicals generated by xanthine-xanthine oxidase or phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), a surface active agent (Triton X-100), and anti-HLA antibodies and complement. With each mechanism of injury, the 3HDOG assay detected significant (P less than 0.01) endothelial cell damage at lower concentrations of the injurious agent than the 51Cr assay. When endothelial monolayers were damaged by xanthine-xanthine oxidase or PMA-activated PMNs, efflux of 3HDOG was reduced (range 71% to 94% reduction) by superoxide dismutase and catalase, indicating that efflux of 3HDOG was mediated by toxic oxygen radicals. When monolayers were damaged with xanthine oxidase in the absence of glucose, a much lower concentration of xanthine oxidase was required to initiate efflux of 3HDOG as compared with xanthine oxidase injury in the presence of glucose. Additional studies compared the 3HDOG assay with 3H-adenine, 3H-leucine, and lactate dehydrogenase (LDH) release when endothelial cells were exposed to toxic oxygen radicals generated by PMA-activated PMNs and xanthine-xanthine oxidase. Again, the 3HDOG assay was more sensitive in detecting in vitro endothelial cell damage. We conclude that the 3HDOG assay is more sensitive than the 51Cr, 3H-adenine, 3H-leucine, or LDH release assays in detecting endothelial cell damage in vitro.
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PMID:In vitro detection of endothelial cell damage using 2-deoxy-D-3H-glucose: comparison with chromium 51, 3H-leucine, 3H-adenine, and lactate dehydrogenase. 383 30

There is evidence that oxygen-derived free radicals may play a role in myocardial ischaemic and reperfusion injury. Major sources of O2 free radicals formation during ischaemia and reperfusion are: the enzyme xanthine oxidase, activated neutrophils and the myocardial mitochondria. However, in the heart there are defense mechanisms against the toxic oxygen metabolites. They include the enzyme superoxide dismutase, catalase and glutathione peroxidase plus endogenous antioxidants like vitamin E, ascorbic acid and cysteine. We have investigated in the isolated rabbit hearts the effects of ischaemia and reperfusion on these defence mechanisms. 90 min of ischaemia and/or hypoxia induced a significant reduction of mitochondrial superoxide dismutase, and of reduced glutathione/oxidized glutathione ratio which was further declined after reperfusion indicating that an oxidative stress has occurred. These alterations are associated with massive tissue and mitochondrial calcium accumulation, loss of mitochondrial function and severe membrane damage. The effects of vitamin E on these parameters have been investigated. Administration of 1.1 mg of dl-alpha-tocopherol acetate showed a protective effect on mitochondrial function but it failed to improve the recovery of mechanical function during reperfusion.
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PMID:Role of oxygen in myocardial ischaemic and reperfusion damage: effect of alpha-tocopherol. 384 29

Preparative chromatographic fractions of human umbilical cord hyaluronic acid (HA) of a molecular weight of 10(6) were subjected to graded oxygen-derived free radical (oxy radical) fluxes produced by: (a) the autoxidation of ferrous ions; (b) the action of xanthine oxidase (XO) on hypoxanthine (HX); and (c) by peripheral blood polymorphonuclear leucocytes that had been stimulated by phorbol myristate acetate (PMA). Analysis by gel chromatography of the products obtained with each of the oxy radical generating systems showed polydispersity in size. The smallest molecules detected had a molecular weight of 10(4). This limiting size was not reduced further by exposure to a second oxy radical flux. The relative proportions of large, medium, and small degradation products were established for various levels of oxy radical flux. Consistently a relatively rapid transition from large to small material was seen on Sepharose 2B chromatography, suggesting an ordered element to the breakdown process. Although the decrease in molecular weight after oxy radical exposure was confirmed by analytical ultracentrifugation, this procedure showed that those samples of lowest viscosity did not have the lowest sedimentation values, possibly reflecting oxy radical-induced repolymerisation. If the size and possibly the conformational characteristics of HA are altered, oxy radical exposure might be expected to alter its biological properties.
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PMID:Depolymerisation products of hyaluronic acid after exposure to oxygen-derived free radicals. 406 91

Treatment of human neutrophils with triphenyltin chloride (TPTCl)-inhibited superoxide (O-2) production stimulated with phorbol myristate acetate (PMA). TPTCl was more potent as inhibitor of O-2 production than other phenyltin compounds. The O-2 production by the xanthine oxidase-acetaldehyde system was not inhibited by TPTCl. This finding indicates that TPTCl does not itself react with O-2. Furthermore, TPTCl did not influence the isolated NADPH oxidase at all, though O-2 production of neutrophils stimulated with PMA in the presence of TPTCl was inhibited. These results indicate that TPTCl inhibits the activation process of the O-2 generating system.
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PMID:Triphenyltin chloride inhibits superoxide production by human neutrophils stimulated with a surface active agent. 631 50

Superoxide radical, generated enzymatically by the action of xanthine oxidase on hypoxanthine, significantly inhibited proteoglycan synthesis by cultured bovine articular cartilage. This inhibition was not due to the generation of uric acid or to the generation of superoxide per se. It was immediate in onset and still evident after six days in culture. The inhibition was similar for both 35S-sulphate and 3H-acetate incorporation into glycosaminoglycans and could not be reversed by addition of beta-D-benzyl xyloside. Protein synthesis was also inhibited.
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PMID:Oxygen free-radicals mediate an inhibition of proteoglycan synthesis in cultured articular cartilage. 633 28

There is much evidence from in vivo and in vitro carcinogenesis studies that active oxygen species play a role in tumor promotion. We tested directly whether superoxide produced extracellularly by xanthine-xanthine oxidase (X-XO) has the capacity to promote initiated mouse embryo C3H/10T1/2 fibroblasts. Cell cultures initiated with either 137Cs gamma-rays or benzo[a]pyrene diol epoxide I were found to transform 3-30 times more effectively when subsequently treated daily for 3 weeks with nontoxic doses of X-XO. Scavengers of active oxygen radicals such as superoxide dismutase or superoxide dismutase in combination with catalase reduced the frequency of appearance of transformed foci by 3-25 times when compared to cultures receiving X-XO alone. These results show that active oxygen species such as superoxide and H2O2 can act in a promotional manner that mimics the effects of the mouse skin promoter phorbol 12-myristate 13-acetate in this system. X-XO also acted as a weak complete carcinogen.
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PMID:Active oxygen acts as a promoter of transformation in mouse embryo C3H/10T1/2/C18 fibroblasts. 642 26


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