Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crude cell-free extracts of nine strains of Streptomyces tested for nitroalkane-oxidizing activity showed production of nitrous acid from 2-nitropropane, 1-nitropropane, nitroethane, nitromethane, and 3-nitropropionic acid. These substrates were utilized in most strains but to a decreasing extent in the order given, and different strains varied in their relative efficiency of oxidation. p-Nitrobenzoic acid, p-aminobenzoic acid, enteromycin, and omega-nitro-l-arginine were not attacked. d-Amino acid oxidase, glucose oxidase, glutathione S-transferase, and xanthine oxidase, enzymes potentially responsible for the observed oxidations in crude cellfree extracts, were present at concentrations too low to play any significant role. A nitroalkane-oxidizing enzyme from streptozotocin-producing Streptomyces achromogenes subsp. streptozoticus was partially purified and characterized. It catalyzes the oxidative denitrification of 2-nitropropane as follows: 2CH(3)CH(NO(2))CH(3) + O(2) --> 2CH(3)COCH(3) + 2HNO(2). At the optimum pH of 7.5 of the enzyme, 2-nitropropane was as good a substrate as its sodium salt; t-nitrobutane was not a substrate. Whereas Tiron, oxine, and nitroxyl radical acted as potent inhibitors of this enzyme, superoxide dismutase was essentially without effect. Sodium peroxide abolished a lag phase in the progress curve of the enzyme and afforded stimulation, whereas sodium superoxide did not affect the reaction. Reducing agents, such as glutathione, reduced nicotinamide adenine dinucleotide, and nicotinamide adenine dinucleotide phosphate, reduced form, as well as thiol compounds, were strongly inhibitory, but cyanide had no effect. The S. achromogenes enzyme at the present stage of purification is similar in many respects to the enzyme 2-nitropropane dioxygenase from Hansenula mrakii. The possible involvement of the nitroalkane-oxidizing enzyme in the biosynthesis of antibiotics that contain a nitrogen-nitrogen bond is discussed.
 ...
PMID:Nitroalkane oxidation by streptomycetes. 3 65

The effect of an antigenic challenge with sheep red blood cells (SRBC) on the activities of cytochrome P-450-dependent and -independent xenobiotic metabolizing enzymes and on lipid peroxidation in the liver was investigated. The studies were carried out using three mouse strains of C57B1/10 and three strains of C3H backgrounds which are cogenic, differing genetically at the H-2 complex. The basal levels of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7-Ec) were different among congenic strains. The activity of 7-Ec was lower in C3H background mice than in B10 background mice. Similarly, the difference due to the strain and the H-2 locus was detected in the activities of P-450-independent enzymes such as malathion and diethyl succinate carboxylesterases, glutathione S-transferase, and epoxide hydrolases in microsomal and cytosolic fractions. The degree of immune responsiveness in these mice was determined by a plaque forming cell assay. Within the same background, the H-2b mouse strain was a high responder and the H-2k a low responder to SRBC. However, treatment with SRBC had no significant depressive effect on P-450-dependent enzyme activities except in C3H/He. Activity of AHH was suppressed in C3H/He mice. Treatment with SRBC had no effect on P-450-independent enzyme activities except for malathion carboxylesterase: the activity was increased in C3H/He and C3H.JK, whereas it was decreased in B10. The basal level of lipid peroxidation was lower in C3H/He and C3H.JK. The treatment produced a significant enhancement in lipid peroxidation in C3H/He, B10 and B10.BR (P less than 0.05) with a concomitant increase in xanthine oxidase activity (P less than 0.05). Thus, the present study revealed that a specific antigenic challenge, unlike non-specific immunostimulants (e.g. poly IC, endotoxin), does not necessarily inhibit P-450-dependent xenobiotic metabolizing enzymes even though antigen challenge increased XO activity and lipid peroxidation. The possible roles of an increase in lipid peroxidation and xanthine oxidase activity in immune response to SRBC and xenobiotic metabolizing enzymes are discussed.
 ...
PMID:Effect of induction of T-cell-dependent antibody with sheep red blood cells on P-450-dependent and -independent xenobiotic metabolizing enzymes. 348 42

The effect of protoporphyrin (PP) administration on the activities of enzymes related to and/or involved in lipid peroxidation and on the content of reduced glutathione (GSH) was investigated in rat liver. PP, at an intravenous dose of 20 mg/kg, increased GSH content, caused a weak suppression of NADPH-cytochrome c reductase activity and a slight increase of gamma-glutamyl transpeptidase activity 24 h after dosing, but had no effect on the activities of other enzymes such as xanthine oxidase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, gamma-glutamylcysteine synthetase or glutathione synthetase. Treatment of rats with diethyl maleate following PP injection resulted in the disappearance of antioxidative action of PP. Furthermore, sinusoidal, but not canalicular, efflux of hepatic GSH was decreased by the PP treatment. The increase of liver GSH content by PP treatment due to the decrease of sinusoidal efflux of GSH from the liver, thus would be involved in the exertion of antioxidative action of PP.
 ...
PMID:Antioxidative effect of protoporphyrin and increase of glutathione in protoporphyrin-administered rat liver. 810 76

To clarify the mechanism of oxidative stress in skeletal muscle atrophied by immobilization, we measured the activities of antioxidant enzymes and xanthine oxidase (XOD) and carried out the cytochemical study of hydrogen peroxide in a typical slow red muscle, the soleus. Male Wistar rats (15 wk old), of which ankle joints of one hindlimb were immobilized in the fully extended position, were killed after 4, 8, or 12 days. The activities of Mn-containing superoxide dismutase (Mn-SOD), Cu-Zn-containing superoxide dismutase (Cu-Zn-SOD), Se-dependent glutathione peroxidase (Se-GSHPx), glutathione S-transferase, catalase, and glutathione reductase were measured spectrophotometrically. The XOD activity and the concentrations of hypoxanthine, xanthine, and urate were measured using a high-performance liquid chromatography. The cytochemical study of hydrogen peroxide in short-term organ culture was performed using an electron microscope. Increased Cu-Zn-SOD and decreased Mn-SOD in atrophy might reflect increased generation of superoxide anions in the cytoplasm rather than in the mitochondria. The source of superoxide anions in the cytoplasm might be the increased superoxide-producing XOD. Enhanced generation of superoxide anions and increased Cu-Zn-SOD activity in atrophy suggested the enhanced generation of hydrogen peroxide in the cytoplasm. Due to the unchanged activity of Se-GSHPx and the unchanged or slightly increased activity of catalase in atrophy, the ability to degrade hydrogen peroxide might not increase so much. Hence, hydrogen peroxide is expected to be increased in atrophy. The cytochemical study supported this expectation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Mechanism of oxidative stress in skeletal muscle atrophied by immobilization. 827 38

Polymorphisms have been detected in a variety of xenobiotic-metabolizing enzymes at both the phenotypic and genotypic level. In the case of four enzymes, the cytochrome P450 CYP2D6, glutathione S-transferase mu, N-acetyltransferase 2 and serum cholinesterase, the majority of mutations which give rise to a defective phenotype have now been identified. Another group of enzymes show definite polymorphism at the phenotypic level but the exact genetic mechanisms responsible are not yet clear. These enzymes include the cytochromes P450 CYP1A1, CYP1A2 and a CYP2C form which metabolizes mephenytoin, a flavin-linked monooxygenase (fish-odour syndrome), paraoxonase, UDP-glucuronosyltransferase (Gilbert's syndrome) and thiopurine S-methyltransferase. In the case of a further group of enzymes, there is some evidence for polymorphism at either the phenotypic or genotypic level but this has not been unambiguously demonstrated. Examples of this class include the cytochrome P450 enzymes CYP2A6, CYP2E1, CYP2C9 and CYP3A4, xanthine oxidase, an S-oxidase which metabolizes carbocysteine, epoxide hydrolase, two forms of sulphotransferase and several methyltransferases. The nature of all these polymorphisms and possible polymorphisms is discussed in detail, with particular reference to the effects of this variation on drug metabolism and susceptibility to chemically-induced diseases.
 ...
PMID:Metabolic polymorphisms. 836 90

Porcine and bovine lens GSTs were compared in the stability against various oxidative stress which is a major factor of cataract formation in order to clarify the role of lens glutathione S-transferase (GST) and its relation to cataractogenesis. Class pi porcine lens GST was inactivated reversibly by biological disulfides, cystine and cystamine, and also inactivated by active oxygen species such as O2- generated through xanthine-xanthine oxidase system and H2O2. On the other hand, class mu bovine lens GST was insensitive to such applied oxidative stress. Furthermore, 1,2-naphthoquinone, which is a metabolite of naphthalene and an actual inducer of naphthalene cataract, strongly inactivated porcine lens GST though it did not affect bovine enzyme. Thus, porcine and bovine lens GSTs had different sensitivity to various oxidative stress which could induce cataract formation. The results suggest that the differential expression of GST isozymes among animals may explain the variation in the cataract formation caused by oxidative stress.
 ...
PMID:Difference in glutathione S-transferase response to oxidative stress between porcine and bovine lens. 847 85

A cDNA encoding mouse butyrophilin was obtained by reverse transcriptase-coupled polymerase chain reaction (RT-PCR) using poly (A)+ RNA from lactating mouse mammary gland as a template and screening a cDNA library with the RT-PCR-amplified fragment as a probe. DNA sequencing and computer analysis revealed that it has a rather long 3'-untranslated sequence and that the carboxy-terminal cytoplasmic domain was well conserved between mouse and bovine butyrophilins. To elucidate the biological function of butyrophilin, the cytoplasmic region expressed as fusion protein with glutathione S-transferase (GST) was purified and incubated with the cell lysate of mouse mammary epithelial cell lines, COMMA-ID and HC11. A 150-kDa protein was shown to specifically associate with the cytoplasmic domain and the protein increased in amount when the cells were treated with basal medium supplemented with lactogenic hormones such as prolactin, insulin and glucocorticoid. N-terminal amino acid sequencing indicated that the protein is xanthine dehydrogenase/oxidase which has been cloned from mouse liver. Further, the cytoplasmic domain also bound xanthine dehydrogenase/oxidase from bovine milk fat globule membrane. These results suggest that butyrophilin might be physiologically associated with xanthine dehydrogenase/oxidase and might function in a complex form in milk fat secretion.
 ...
PMID:Carboxy-terminal cytoplasmic domain of mouse butyrophilin specifically associates with a 150-kDa protein of mammary epithelial cells and milk fat globule membrane. 854 2

In the present study, we investigated the effects of high levels of dietary fish oil on the growth of MX-1 human mammary carcinoma and its response to mitomycin C (MC) treatment in athymic mice. We found that high levels of dietary fish oil (20% menhaden oil + 5% corn oil, w/w) compared to a control diet (5% corn oil, w/w) not only lowered the tumor growth rate, but also increased the tumor response to MC treatment. We also found that high levels of dietary fish oil significantly increased the activities of tumor xanthine oxidase and DT-diaphorase, which are proposed to be involved in the bioreductive activation of MC. Since menhaden oil is highly unsaturated, its intake caused a significant increase in the degree of fatty acid unsaturation in tumor membrane phospholipids. This alteration in tumor membrane phospholipids made the tumor more susceptible to oxidative stress, as indicated by the increased levels of both endogenous lipid peroxidation and protein oxidation after feeding the host animals the menhaden oil diet. In addition, the tumor antioxidant enzyme activities, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPOx), and glutathione S-transferase peroxidase (GSTPx), were all significantly enhanced by feeding a diet high in fish oil. MC treatment caused further increases in tumor lipid peroxidation and protein oxidation, as well as in the activities of CAT, SOD, GPOx, and GSTPx, suggesting that MC causes oxidative stress in this tumor model which is exacerbated by feeding a diet high in menhaden oil. Thus, feeding a diet rich in menhaden oil decreased the growth of human mammary carcinoma MX-1, increased its responsiveness to MC, and increased its susceptibility to endogenous and MC-induced oxidative stress, and increased the tumor activities of two enzymes proposed to be involved in the bioactivation of MC, that is, DT-diaphorase and xanthine oxidase. These findings support a role of these two enzymes in the bioactivating of MC and indicate that the type of dietary fat may be important in tumor response to therapy.
 ...
PMID:Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary carcinoma MX-1. 856 32

In our studies to find natural compounds with chemopreventive efficacy in foods, using azoxymethane (AOM)-induced colonic aberrant crypt foci and colonic mucosal cell proliferation as biomarkers, a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate (ACA), present in the edible plant Languas galanga from Thailand was found to be effective. This study was conducted to test the ability of ACA to inhibit AOM-induced colon tumorigenesis when it was fed to rats during the initiation or post-initiation phase. Male F344 rats were given three weekly s.c. injections of AOM (15 mg/kg body weight) to induce colonic neoplasms. They were fed diet containing 100 or 500 ppm ACA for 4 weeks, starting one week before the first dosing of AOM (the initiation feeding). The other groups were fed the ACA diet for 34 weeks, starting one week after the last AOM injection (the post-initiation feeding). At the termination of the study (week 38), AOM had induced 71% incidence of colonic adenocarcinoma (12/17 rats). The initiation feeding with ACA caused significant reduction in the incidence of colon carcinoma (54% inhibition by 100 ppm ACA feeding and 77% inhibition by 500 ppm ACA feeding, P = 0.03 and P = 0.001, respectively). The post-initiation feeding with ACA also suppressed the incidence of colonic carcinoma (45% inhibition by 100 ppm ACA feeding and 93% inhibition by 500 ppm ACA feeding, P = 0.06 and P = 0.00003, respectively). Such inhibition was dose-dependent and was associated with suppression of proliferation biomarkers, such as ornithine decarboxylase activity in the colonic mucosa, and blood and colonic mucosal polyamine contents. ACA also elevated the activities of phase II enzymes, glutathione S-transferase (GST) and quinone reductase (QR), in the liver and colon. These results indicate that ACA could inhibit the development of AOM-induced colon tumorigenesis through its suppression of cell proliferation in the colonic mucosa and its induction of GST and QR. The results confirm our previous finding that ACA feeding effectively suppressed the development of colonic aberrant crypt foci. These findings suggest possible chemopreventive ability of ACA against colon tumorigenesis.
 ...
PMID:Chemoprevention of azoxymethane-induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate. 936 29

Free radicals have previously been shown to kill the immature stages of the trematode, Schistosoma mansoni but their effect on newly excysted juvenile (NEJ) flukes of Fasciola hepatica has not been established. Using acetaldehyde and xanthine oxidase to chemically generate reactive oxygen intermediates (ROI), up to 61% of NEJ were killed but only when exposed to high levels of ROI. At low concentrations of acetaldehyde and xanthine oxidase as sources of reactive oxygen intermediates, only 6-29% of NEJ were killed compared with 70-92% of schistosomula. Incubation with lipopolysaccharide (LPS)-stimulated rat peritoneal lavage cells (PLCs) killed only 7-15% of NEJ whereas 78-87% of schistosomula were killed under the same conditions by a mechanism dependent on the production of reactive nitrogen intermediates. Relative to immature and adult parasites, NEJ expressed 2.5-20-fold lower levels of superoxide dismutase and glutathione S-transferase but no catalase activity was detected. Incubation of NEJ with inhibitors of peroxidases and glutathione metabolism increased the mean killing of NEJ by LPS-stimulated rat PLCs to 40-75%. These results demonstrate that, in comparison to schistosomula of S. mansoni, NEJ of F. hepatica are relatively resistant to killing by free radicals and this resistance could, in part, be due to the activity of oxidant scavenger enzymes of NEJ.
 ...
PMID:Juvenile Fasciola hepatica are resistant to killing in vitro by free radicals compared with larvae of Schistosoma mansoni. 1084 8


1 2 3 4 5 Next >>