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)

It has been established that papaverine as well as other xenobiotics (dexamethasone and nitrosodimethylamine) [figure: see text] provoked the thymocyte death like apoptosis. The increase of the quantity of double-strand, single-strand DNA breaks and low molecular weight fragments of DNA preceded cell death. In papaverine-induced process of thymocyte apoptosis the total activity of xanthine oxidase in thymocytes strongly elevated long before their death, the conversion of xanthine dehydrogenase (D-form) to xanthinoxidase (O-form) and accumulation of O-form in the cultural medium took place. Direct stimulating effect of papaverine on O-form of enzyme in thymocyte lysate was revealed. The used digitonin thymocytes were divided into cytoplasmic and structural component fractions. It was shown that about 80% of total xanthinoxidase activity was concentrated in cytoplasma while only 20% of its activity was found in structural components. More higher ratio of xanthinoxidase/xanthindehydrogenase (XO/XDH) was observed and papaverine-induced changes of these enzyme forms activities were expressed more brightly in the structural components, than in the thymocyte cytoplasma. During the process of developing thymocytes apoptosis caused by papaverine the reaction of lipid peroxidation was intensified. XO-hypoxanthin system displaying prooxidant influence on cells increased the cytotoxic effect of papaverine but the presence of allopurinol or catalase and superoxidedismutase decreased it. Besides, cytotoxic action on thymocytes of allopurinol itself as well as hypoxanthin itself was revealed.
 ...
PMID:[Role of xanthine oxidase and xanthine dehydrogenase systems in thymocyte apoptosis, induced by papaverine]. 1120 Apr 84

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, induced xanthine oxidase and xanthine dehydrogenase (XO/XDH) activities, in addition to ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in liver of mice. When TCDD was given to mice as a single oral dose of 40 microg/kg, the activities of XO and XDH increased about threefold within 3 days and the increased levels were maintained for 4 weeks. The treatment of mice with 3-methylcholanthrene also induced XO/XDH activities, but phenobarbital and dexamethasone had no effect. The level of aldehyde oxidase, a molybdenum flavoenzyme related to XO/XDH, in mouse liver was also enhanced about 1.5-fold by TCDD treatment. The inducing effect of TCDD and 3-methylcholanthrene was not observed in null mice (AhR(-/-)), which lack the AhR gene. XO and XDH activities were induced by TCDD in heterozygous mice (AhR(+/-)). The lipid peroxidation in liver was stimulated by TCDD. The induction of XO and XDH, which produces reactive oxygen species, may contribute to the various toxicities of TCDD.
 ...
PMID:Aryl hydrocarbon receptor (AhR)-mediated induction of xanthine oxidase/xanthine dehydrogenase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1124 47

Studies have been made on the possible involvement of malondialdehyde (MDA) and (E)-4-hydroxynon-2-enal (HNE), two terminal compounds of lipid peroxidation, in modifying xanthine oxidoreductase activity through interaction with the oxidase (XO) and/or dehydrogenase (XDH) forms. The effect of the two aldehydes on XO (reversible, XO(rev), and irreversible, XO(irr)) and XDH was studied using xanthine oxidase from milk and xanthine oxidoreductase partially purified from rat liver. The incubation of milk xanthine oxidase with these aldehydes resulted in the inactivation of the enzyme following pseudo-first-order kinetics: enzyme activity was completely abolished by MDA (0.5-4 mM), while residual activity (5% of the starting value) associated with an XO(irr) form was always observed when the enzyme was incubated in the presence of HNE (0.5-4 mM). The addition of glutathione to the incubation mixtures prevented enzyme inactivation by HNE. The study on the xanthine oxidoreductase partially purified from rat liver showed that MDA decreases the total enzyme activity, acting only with the XO forms. On the contrary HNE leaves the same level of total activity but causes the conversion of XDH into an XO(irr) form.
 ...
PMID:Mechanisms of action of malondialdehyde and 4-hydroxynonenal on xanthine oxidoreductase. 1133 8

The activity of xanthine oxidoreductases (xanthine oxidase, XO, EC 1.2.3.2 and xanthine dehydrogenase, XDH, EC 1.1.1.204) in partially purified extracts of Gonyaulax polyedra was measured over 24 h both in a light:dark cycle and in constant light. This is the first demonstration of xanthine oxidoreductase in a unicellular alga. The activity of the O2-dependent form (XO) was found to be 15 times higher in light than in darkness. The same time-of-day specific differences persisted in constant light, demonstrating a control of XO by the circadian clock. In contrast, the activity of the NAD-dependent form (XDH) is not under circadian control. Because pharmacological inhibition of XO also blocks the effect of blue light on the Gonyaulax circadian clock, the possible relationship between XO and light reception in this unicellular alga will be discussed.
 ...
PMID:The flavo-enzyme xanthine oxidase is under circadian control in the marine alga Gonyaulax. 1206 1

Hypoxia causes up-regulation and activation of xanthine dehydrogenase/xanthine oxidase (XDH/XO) in vitro and in the lungs in vivo. This up-regulation, and the likely corresponding production of reactive oxygen species, may underlie the pathogenesis of an array of disorders. Thus, compounds that prevent hypoxia-induced increase in XDH/XO activity may provide a therapeutic strategy in such disorders. The antioxidant properties of estrogens have been demonstrated in several studies. However, the effect of these compounds on XDH/XO has not been explored previously. The aim of this study was to investigate the effects of estrogen on hypoxia-induced increase in XDH/XO activity. Rat pulmonary artery microvascular endothelial cells were exposed to normoxia or hypoxia in the presence or absence of 17beta- or 17alpha-estradiol. The XDH/XO enzyme and gene promoter activities were measured in different groups of cells. Hypoxia caused a twofold increase in XDH/XO enzymatic and promoter activity. Either of the estradiol stereoisomers prevented the hypoxia-induced increase in XDH/XO enzymatic activity, but not the promoter activity. ICI 182,780, an antagonist of the estrogen receptor, failed to block the inhibitory effect of estradiol on XDH/XO. In conclusion, 17alpha- and 17beta-estradiol modulate the hypoxia-induced regulation of XDH/XO activity at a posttranscriptional level by a receptor-independent mechanism.
 ...
PMID:Estrogen modulates xanthine dehydrogenase/xanthine oxidase activity by a receptor-independent mechanism. 1458 43

The small intestine exhibits numerous morphological and functional alterations during diabetes. Oxidative stress, a factor implicated in the pathogenesis of diabetic complications may contribute towards some of these alterations. We therefore investigated the occurrence of oxidative stress in the small intestine during diabetes by measuring the extent of oxidative damage as well as the status of the antioxidant defense system. Significant increases in lipid peroxidation (four-fold) as measured by TBARS and protein oxidation (38%) as measured by protein carbonyl content were observed after 6 weeks of diabetes. A distinct elevation in the activities of catalase (123.9%) and superoxide dismutase (71.9%) and a decline in the activity of glutathione peroxidase (67.7%) were also observed. The steady state mRNA levels of these enzymes measured by RT-PCR were, however, unchanged suggesting the absence of transcriptional control. In contrast, no changes in the levels of protein and non-protein thiols as well as the activities of glutathione reductase and glutathione-S-transferase were detected. Interestingly, decreases in the activities of xanthine oxidase (XO; 25.7%) and xanthine dehydrogenase (XDH; 42.6%) indicate that they do not contribute significantly to oxidative damage. The results thus reveal the occurrence of oxidative stress in the small intestine during diabetes and suggest its possible involvement in some of the accompanying functional alterations.
 ...
PMID:Oxidative damage and altered antioxidant enzyme activities in the small intestine of streptozotocin-induced diabetic rats. 1459 35

A 43-year-old xanthinuric female was referred to our department because of hypouricemia. Routine laboratory data showed hypouricemia, a high level of plasma oxypurines, decreased urinary uric acid excretion, and increased urinary oxypurine excretion, with xanthine dehydrogenase activity in the duodenal mucosa below the limits of detection. In addition, allopurinol was not metabolized. From these findings, the patient was diagnosed with xanthinuria type II. To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency, a cDNA sequence encoding XDH/XO, aldehyde oxidase (AO), and molybdenum cofactor sulferase (MCS), as well as immunoblotting analysis for XDH/XO protein, obtained from duodenal mucosa samples were performed. The XDH/XO cDNA and AO cDNA sequences of the xanthinuric patient were consistent with previously reported ones, whereas the MCS cDNA sequence revealed a point mutation of G to C in nucleotide 466, which changed codon 156 from GCC (Ala) to CCC (Pro). In addition, the MCS genomic DNA sequence including the site of the mutation revealed the same, suggesting that the xanthinuric patient was homozygous for this mutation. Such findings have not been previously reported for patients with xanthinuria type II.
 ...
PMID:Identification of a new point mutation in the human molybdenum cofactor sulferase gene that is responsible for xanthinuria type II. 1462 14

The hypouricemic actions of Biota orientalis (BO) extract and its flavonoid constituents quercetin and rutin, were in vivo examined using oxonate-induced hyperuricemic mice. Quercetin and rutin, when administered three times orally to the oxonate-induced hyperuricemic mice, were able to elicit dose-dependent hypouricemic effects. The effects of quercetin and rutin were more potent than that of Biota orientalis extract at the same dose of 100 mg/kg. At doses of 50 mg/kg of quercetin or above, or at doses of 100 mg/kg of rutin or above, the serum urate levels of the oxonate-pretreated mice were not different from normal mice. In addition, Biota orientalis extract, quercetin and rutin, when tested in vivo on mouse liver homogenates, elicited significant inhibitory actions on the xanthine dehydrogenase/xanthine oxidase (XDH/XO) activities. The effects of quercetin and rutin resulted less potent than that of allopurinol. However, intraperitoneal administration at the same scheme did not produce any observable hypouricemic effect. These hypouricemic effects are partly due to the inhibition of XDH/XO activities in mouse liver. The pharmacological profile of the flavonoids is partly different from that of allopurinol. Such hypouricemic action and inhibition of the enzyme activity of quercetin and rutin may be responsible for a part of the beneficial effects of Biota orientalis extract on hyperuricemia and gout. The effects of quercetin and rutin on serum urate levels in hyperuricemic mice induced by oxonate and the inhibition of enzyme activities in mouse liver are discussed in relation to their absorption and metabolism, and their potential application to treat gout and hyperuricemia.
 ...
PMID:Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. 1518 18

We utilized a newborn rat model of hypoxia/reoxygenation (H/R) that resembles human necrotizing enterocolitis (NEC) to investigate the effects of omeprazole and/or gentamicin on the formation of free oxygen radicals (FOR) and bowel histopathology. For H/R, 1-day-old rats were placed into a chamber of 100% CO2 for 5 min, then they were reoxygenized for the next 5 min. The rats (n = 70) were divided into seven groups: group 1 (control), group 2 (H/R), group 3 (omeprazole), group 4 (H/R + omeprazole), group 5 (gentamicin), group 6 (H/R + gentamicin), group 7 (H/R + omeprazole + gentamicin). Gentamicin and/or omeprazole were given orally for 3 days, then all animals were killed; bowel specimens were harvested. Histopathologic injury scores (HIS) and malonyldialdehyde (MDA) and XO/(XO+XDH) rates (XO; xanthine oxidase, XDH; xanthine dehydrogenase) were measured, which reflect the FOR levels. In group 2, the HIS was significantly higher than groups 4 and 6. The mean MDA values in groups 1-7 were as follows: 54.16, 104.2, 56.85, 63.43, 62.31, 76.85, 79.13, respectively. The mean XO/(XO + XDH) levels were 0.306, 0.461, 0.286, 0.335, 0.323, 0.410, 0.375 from groups 1 -7, respectively. Group 2 rats had significantly more MDA and XO/(XO + XDH) rates versus other groups (P < 001). Histopathologic injury and biochemical results were significantly more severe in group 2 than in groups 4 and 6 (P < 001). There was no difference between groups 1 and 4 according to XO/(XO + XDH) rates. In newborn rats, H/R produces FOR, which cause serious intestinal damage. Omeprazole and/or gentamicin reduce biochemical and histopathologic bowel damage. This effect was more obvious in omeprazole treated rats. We think omeprazole may open new insights into the treatment of H/R related bowel injuries like NEC.
 ...
PMID:Effects of omeprazole and gentamicin on the biochemical and histopathological alterations of the hypoxia/ reoxygenation induced intestinal injury in newborn rats. 1620 29

Xanthine dehydrogenase/oxidase (XDH/XO) is associated with various pathological conditions related to the endothelial injury. However, the molecular mechanism underlying the activation of XDH/XO by hypoxia remains largely unknown. In this report, we determined whether the Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling pathway is involved in hypoxia-induced activation of XDH/XO in primary cultures of lung microvascular endothelial cells (LMVEC). We found that hypoxia significantly increased interleukin 6 (IL6) production in a time-dependent manner in LMVEC. Hypoxia also markedly augmented phosphorylation/activation of JAKs (JAK1, JAK2 and JAK3) and the JAK downstream effectors STATs (STAT3 and STAT5). Hypoxia-induced activation of STAT3 was blocked by IL6 antibodies, the JAK inhibitor AG490 and the suppressor of cytokine signaling 3 (SOCS3), implying that hypoxia-promoted IL6 secretion activates the JAK/STAT pathway in LMVEC. Phosphorylation and DNA-binding activity of STAT3 were also inhibited by the p38 MAPK inhibitor SB203580 and the phosphatidylinositol 3-kinase inhibitor LY294002, suggesting that multiple signaling pathways involved in STAT activation by hypoxia. Importantly, hypoxia promoted XDH/XO activation in LMVEC, which was markedly reversed by inhibiting the JAK-STAT pathway using IL6 antibodies, AG490 and SOCS3. These data demonstrated that JAKs, STATs and XDH/XO were sequentially activated by hypoxia. These data provide the first evidence indicating that the JAK-STAT pathway is involved in hypoxia-mediated XDH/XO activation in LMVEC.
 ...
PMID:Sequential activation of JAKs, STATs and xanthine dehydrogenase/oxidase by hypoxia in lung microvascular endothelial cells. 1792 Mar 30


<< Previous 1 2 3 4 5 6 Next >>