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)

To evaluate the regulation of endothelial cell Cu,Zn-SOD, we have exposed bovine pulmonary artery endothelial cells in culture to hyperoxia and hypoxia, second messengers or related agonists, hormones, free radical generating systems, endotoxin, and cytokines and have measured Cu,Zn-SOD protein of these cells by an ELISA developed in our laboratory. Control preconfluent and confluent cells in room air contained 196 +/- 18 ng Cu,Zn-SOD/10(6) cells. A23187 (0.33 microM), forskolin (10 microM), isobutylmethylxanthine (0.1 mM), dexamethasone (1 microM), triiodothyronine (1 microM) and retinoic acid (1 microM) failed to alter this level of Cu,Zn-SOD. Exposure to anoxia and hyperoxia both elevated the level approximately 1.5-2.0-fold over 20% oxygen-exposed controls at 48-72 hr. Similarly, exposures to glucose oxidase (0.0075 units/ml), menadione (12.5 microM), xanthine-xanthine oxidase (10 microM, 0.03 units/ml) and H2O2 (0.0005%) increased the level up to two-threefold over controls at 24-48 hr. Lipopolysaccharide, TGF beta 1, TNF alpha, and Il-1 also increased levels of cellular Cu,Zn-SOD, but only in proliferating cells. Il-2, Il-4, interferon-gamma, and GM-CSF had no effect on Cu,Zn-SOD. All treatments that elevated SOD resulted in inhibition of cellular growth, but decreased growth of cells at confluence alone was not associated with increased Cu,Zn-SOD. We propose from these studies that Cu,Zn-SOD of endothelial cells is not under conventional second messenger or hormonal regulation, but that up-regulation of the enzyme is associated with (and perhaps stimulated by) free-radical or oxidant production that also may be influenced by availability of certain cytokines under replicating conditions.
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PMID:Regulation of Cu,Zn-superoxide dismutase in bovine pulmonary artery endothelial cells. 133 80

In the regulation of GTP biosynthesis, complex interactions are observed. A major factor is the behavior of the activity of IMPDH, the rate-limiting enzyme of de novo GTP biosynthesis, and the activity of GPRT, the salvage enzyme of guanylate production. The activities of GMP synthase, GMP kinase and nucleoside-diphosphate kinase are also relevant. In neoplastic transformation, the activities and amounts of all these biosynthetic enzymes are elevated as shown by kinetic assays and by immunotitration for IMPDH. In cancer cells, the up-regulation of guanylate biosynthesis is amplified by the concurrent decrease in activities of the catabolic enzymes, nucleotidase, nucleoside phosphorylase, and the rate-limiting purine catabolic enzyme, xanthine oxidase. The up-regulation of the capacity for GTP biosynthesis is also manifested in the stepped-up capacity of the overall pathways of de novo and salvage guanylate production. The linking with neoplasia is also seen in the elevation of the activities of IMPDH and GMP synthase and de novo and salvage pathways as the proliferative program is expressed as cancer cells enter log phase in tissue culture. The activity of GMP reductase showed no linkage with neoplastic or normal cell proliferation; however, in induced differentiation in HL-60 cells the activity increased concurrently with the decline in the activity of IMPDH. This reciprocal regulation of the two enzymes is observed in differentiation induced by retinoic acid, DMSO or TPA in HL-60 cells. In support of enzyme-pattern-targeted chemotherapy, evidence was provided for synergistic chemotherapy with tiazofurin (inhibitor of IMPDH) and hypoxanthine (competitive inhibitor of GPRT and guanine salvage activity) in patients and in tissue culture cell lines. These investigations should contribute to the clarification of the controlling factors of GMP biosynthesis, the role of the various enzymes, the behavior of GMP reductase in mammalian cells and the application of the approaches of enzyme-pattern-targeted chemotherapy in patients.
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PMID:Regulation of GTP biosynthesis. 135 38

NAD(P)-linked aldehyde dehydrogenases catalyze the oxidation of a wide variety of aldehydes. Thirteen of these enzymes have been identified in mouse tissues; eleven are found in the liver. Some are substrate-nonspecific; others are relatively substrate-specific. The present investigation sought to determine which of these enzymes are operative in catalyzing the oxidation of retinaldehyde to retinoic acid, a metabolite of vitamin A that promotes the differentiation of epithelial and other cells. Spectrophotometric and HPLC assays were used for this purpose. Enzyme-catalyzed oxidation of retinaldehyde (25 microM) was restricted to the cytosol (105,000 g supernatant fraction) and occurred at a rate of 211 nmol/min/g liver; oxidation of acetaldehyde (4 mM) by this fraction proceeds about ten times faster. At least 90% of this activity was NAD dependent. Of the approximately 10% that was apparently NAD independent, two-thirds was inhibited by 1 mM pyridoxal, a known inhibitor of aldehyde oxidase. Of the six cytosolic aldehyde dehydrogenases, only two, viz. AHD-2 and AHD-7, catalyzed the oxidation of retinaldehyde to retinoic acid. An additional NAD-dependent enzyme, viz. xanthine oxidase (dehydrogenase form), also catalyzed the reaction. Catalysis by AHD-2 accounted for more than 90% of the total NAD-dependent activity. Km values were 0.7, 0.6 and 0.9 microM, respectively, for the AHD-2-, AHD-7- and xanthine oxidase (dehydrogenase form)-catalyzed reaction. AHD-4, an aldehyde dehydrogenase found in the cytosol of mouse stomach epithelium and cornea, did not catalyze the reaction.
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PMID:Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid. 188 36

Several lines of indirect evidence implicate vitamin A intoxication, associated mainly with impaired renal function, in the etiopathogenesis of gouty arthritis. The enzyme xanthine oxidase is involved not only in the conversion of xanthine to uric acid but also in that of retinol to its more toxic metabolite, retinoic acid. Retinoic acid should therefore be present in high concentration in hyperuricemic states.
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PMID:Gout and vitamin A intoxication: is there a connection? 206 76

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

The biochemical basis for the cancer chemopreventive and anti-cancer activities of glucarate, retinoids (13-cis-retinoic acid, hydroxyphenyl retinamide) and their synergistic combination, has been evaluated. Neither alone nor in combination did these agents affect the level in the rat, of enzymes which are (a) known to correlate with reduced risk of carcinogenesis (detoxification enzyme, catalase, glutathione reductase) nor (b) enzymes which correlate with increased risk of carcinogenesis (beta-glucuronidase, xanthine oxidase, glucose-6-phosphate dehydrogenase). Retinoids, but neither glucarate nor its lactone inhibited free radical-induced lipid peroxidation. Both agents alone and synergistically in combination, raise cellular cAMP levels, repress protein kinase C and more generally inhibited DNA synthesis.
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PMID:Basis for the anti-tumor and chemopreventive activities of glucarate and the glucarate:retinoid combination. 851 53

Milk xanthine oxidase (xanthine: oxygen oxidoreductase; XO; EC 1.1.3.22) was found to catalyze the conversion of retinaldehyde to retinoic acid. The ability of XO to synthesize all trans-retinoic acid efficiently was assessed by its turnover number of 31.56 min-1, determined at pH 7.0 with 1 nM XO and all trans-retinaldehyde varying between 0.05 to 2 microM. The determination of both retinoid and purine content in milk was also considered in order to correlate their concentrations with kinetic parameters of retinaldehyde oxidase activity. The velocity of the reaction was dependent on the isomeric form of the substrate, the all trans- and 9-cis-forms being the preferred substrates rather than 13-cis-retinaldehyde. The enzyme was able to oxidize retinaldehyde in the presence of oxygen with NAD or without NAD addition. In this latter condition the catalytic efficiency of the enzyme was higher. The synthesis of retinoic acid was inhibited 87% and 54% by 4 microM and 2 microM allopurinol respectively and inhibited 48% by 10 microM xanthine in enzyme assays performed at 2 microM all trans-retinaldehyde. The Ki value determined for xanthine as an inhibitor of retinaldehyde oxidase activity was 4 microM.
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PMID:Xanthine oxidase catalyzes the synthesis of retinoic acid. 1169 48

The present paper assesses the chemopreventive potential of retinoic acid on benzoyl peroxide (BPO)-induced cutaneous tumor promotion response and oxidative stress in murine skin. In this study, we have shown the activities of cutaneous antioxidant enzymes and phase II metabolizing enzymes and the glutathione content were decreased while epidermal ornithine decarboxylase (ODC) activity and DNA synthesis were induced in benzoyl peroxide treated animals. Topical application of retinoic acid resulted in significant inhibition of benzoyl peroxide-induced epidermal ornithine decarboxylase activity and DNA synthesis. Application of retinoic acid at three different doses prior to the application of benzoyl peroxide recovered the depleted level of glutathione, inhibited activities of antioxidant and phase II metabolizing enzymes, thus resulting in significant inhibition of oxidative stress in dose dependent manner. Enhanced susceptibility of cutaneous microsomal lipid peroxidation and xanthine oxidase activity were significantly reduced (P > 0.05). The antimutagenic effect of retinoic acid was tested against benzoyl peroxide mediated mutagenicity in Salmonella typhimurium strain TA-98 and TA-100 using 3-methyl cholanthrene-induced murine skin (S9 fraction) as the metabolic activation system. Indeed, with the addition of various concentrations of retinoic acid there was significant reduction in the number of revertants per plate in concentration dependent manner. In summary, our data indicates that retinoic acid may exhibit cancer chemopreventive activity in skin tumorigenesis model.
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PMID:13-cis Retinoic acid ameliorates benzoyl peroxide-induced oxidative stress and hyperproliferative response in murine skin: a chemopreventive study. 1522

Oxidative stress in the small intestine can result in altered cell proliferation, migration, and differentiation of villus-crypt cells. Retinoid metabolism is recognized as an important mediator of cellular differentiation in the intestine. This study examined the effect of oxidative stress in retinoid metabolism in a surgical stress model. Surgical stress was performed by handling the intestine as done during laparotomy. Villus-crypt cells were isolated at different time periods and various retinoid concentrations in the cell homogenate and the retinoic acid forming enzymes were quantitated using HPLC. Surgical stress resulted in altered retinoid levels in various cell populations in the small intestine at 1 and 12h. The activity of alkaline phosphatase and retinal oxidase was also altered at these time points and all these changes were prevented by inhibiting superoxide generation using xanthine oxidase inhibitor, allopurinol. These studies suggest that alterations seen in enterocytes during surgical stress may be mediated by changes in retinoid metabolism.
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PMID:Surgical stress-induced alterations in retinoid metabolism in the small intestine: role of oxygen free radicals. 1563 30

In mammals, xanthine oxidase (E.C. 1.17.3.2) catalyzes the hydroxylation of a wide variety of heterocyclic substrates such as purines, pyrimidines, and pterins, in addition to aldehydes [1] as all-trans-retinaldehyde [2-5]. Here, we show that buttermilk xanthine oxidase was capable to oxidizing all-trans-retinol (t-ROL) to all-trans-retinaldehyde (t-RAL) that was successively oxidized to all-trans-retinoic acid (t-RA). A rise in the enzyme activity, when t-ROL-CRBP complex was assayed, with respect to the free t-ROL, was observed. Furthermore, treatment of the enzyme with Na2S and glutathione resulted in a significant increment in catalytic activity toward t-ROL and t-RAL, due to the reconstitution of the native structural organization of the molybdenum centre of molybdopterin cofactor of the desulfo form of xanthine oxidase.
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PMID:Xanthine oxidase catalyzes the oxidation of retinol. 1784 15


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