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)

Two principal pathways of Ca2+ release from the sarcoplasmic reticulum of excitable and non-excitable cells have been described: one pathway dependent on the second messenger D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), and a second pathway sensitive to Ca2+ and regulated by caffeine and ryanodine. It was found that the Ca(2+)-pump activity of vascular smooth muscle sarcoplasmic reticulum is inhibited by superoxide anion radicals (O2.-); however, the effects of reactive oxygen intermediates on sarcoplasmic reticulum Ca2+ release in vascular muscle cells are not well defined. The purpose of the present study was to evaluate the effects of reactive oxygen intermediates generated from the hypoxanthine/xanthine oxidase reaction system on contractions induced by caffeine, Ins(1,4,5)P3 and norepinephrine in staphylococcal alpha-toxin-permeabilized rabbit mesenteric arteries. This system generates O2.-, H2O2, and hydroxyl radicals. We wished to identify which class of reactive oxygen intermediates is responsible for the associated loss of vascular smooth muscle contractile function. Caffeine and Ins(1,4,5)P3 produced a transient contraction when the sarcoplasmic reticulum of the permeabilized, preparations was preloaded with pCa 7.0 solution for 5 min before washing with 0.5 mM EGTA solution; norepinephrine also produced a transient contraction. Exposure of the preparations to hypoxanthine/xanthine oxidase (for 30 min) attenuated caffeine-induced contraction, but was without effect on Ins(1,4,5)P3-induced contraction. The observed effect of hypoxanthine/xanthine oxidase exposure was superoxide dismutase-inhibitable, suggesting O2.- involvement. Hypoxanthine/xanthine oxidase also inhibited norepinephrine-induced contraction. The effect of hypoxanthine/xanthine oxidase on norepinephrine contraction was protected by catalase, but not by superoxide dismutase and dimethyl sulfoxide; exogenously added H2O2 mimicked the effect of hypoxanthine/xanthine oxidase exposure. H2O2, added exogenously, was without effect on Ins(1,4,5)P3-induced contraction. It is suggested that the pathway of Ca2+ release from the sarcoplasmic reticulum dependent on Ins(1,4,5)P3 is insensitive to O2.-. Instead, caffeine-induced Ca2+ release mechanisms may be susceptible to O2.- and H2O2, rather than O2.- and hydroxyl radicals, may be the active agent in the norepinephrine-induced contraction. Our results are also consistent with the view that the attenuation by H2O2 of the norepinephrine-induced contraction may be linked to the receptor-associated pathway of Ins(1,4,5)P3 formation, but not to degradation processes of Ins(1,4,5)P3.
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PMID:Susceptibility of caffeine- and Ins(1,4,5)P3-induced contractions to oxidants in permeabilized vascular smooth muscle. 904 2

The effect of allopurinol to inhibit purine metabolism via the xanthine oxidase pathway in neonates with severe, progressive hypoxemia during rescue and reperfusion with extracorporeal membrane oxygenation (ECMO) was examined. Twenty-five term infants meeting ECMO criteria were randomized in a double-blinded, placebo-controlled trial. Fourteen did not receive allopurinol, whereas 11 were treated with 10 mg/kg after meeting criteria and before cannulation, in addition to a 20-mg/kg priming dose to the ECMO circuit. Infant plasma samples before cannulation, and at 15, 30, 60, and 90 min, and 3, 6, 9, and 12 h on bypass were analyzed (HPLC) for allopurinol, oxypurinol, hypoxanthine, xanthine, and uric acid concentrations. Urine samples were similarly evaluated for purine excretion. Hypoxanthine concentrations in isolated blood-primed ECMO circuits were separately measured. Hypoxanthine, xanthine, and uric acid levels were similar in both groups before ECMO. Hypoxanthine was higher in allopurinol-treated infants during the time of bypass studied (p = 0.022). Xanthine was also elevated (p < 0.001), and uric acid was decreased (p = 0.005) in infants receiving allopurinol. Similarly, urinary elimination of xanthine increased (p < 0.001), and of uric acid decreased (p = 0.04) in treated infants. No allopurinol toxicity was observed. Hypoxanthine concentrations were significantly higher in isolated ECMO circuits and increased over time during bypass (p < 0.001). This study demonstrates that allopurinol given before cannulation for and during ECMO significantly inhibits purine degradation and uric acid production, and may reduce the production of oxygen free radicals during reoxygenation and reperfusion of hypoxic neonates recovered on bypass.
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PMID:Purine metabolism and inhibition of xanthine oxidase in severely hypoxic neonates going onto extracorporeal membrane oxygenation. 909 53

Glutamate-mediated excitotoxicity is associated with adenosine triphosphate (ATP) degradation and generation of oxygen radicals. Hypoxanthine and lactate depict energetic impairment, while xanthine and uric acid reflect activity of radical producing xanthine oxidase. Cerebrospinal fluid (CSF) glutamate, hypoxanthine, lactate, xanthine, and uric acid were investigated in neurological patients. In multiple sclerosis, myelopathy, stroke, epilepsy and viral meningitis glutamate, hypoxanthine, xanthine, and uric acid are increased 2-3-fold compared to controls. Lactate is only elevated in meningitis. Normal lactate dehydrogenase (LDH) levels and absent correlation between the albumin ratio and neurochemical parameters exclude an artificial increase due to cell lysis and barrier damage. Absent correlation between neurochemical parameters within each patient group is most likely related to preserved glial and neuronal uptake mechanisms. CSF hypoxanthine, xanthine, and uric acid levels appear superior to lactate in reflecting glutamate-mediated excitotoxicity in neurological patients.
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PMID:Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases. 946 46

Nitric oxide (NO) has cytotoxic effects but NO producing neurons are resistant to NO toxicity. These results suggest the presence of self-protecting factors for NO toxicity. Recently, 6R-tetrahydrobiopterin (6R-BH4), a cofactor for NO synthase (NOS), has been reported to degrade NO raising the possibility that 6R-BH4 acts as a self-protecting factor for NO toxicity. In PC12 cells which have NOS, three-day culture with sodium nitroprusside (SNP) or NOC-12, NO generators, at 10-100 microM increased nitrite and nitrate concentrations in the culture medium and induced death of PC12 cells. Coadministration of 6R-BH4 (10 or 30 microM) with SNP or NOC-12 prevented cell death with reduction of nitrite and nitrate in the medium. Inhibition of 6R-BH4 synthesis by 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor for GTP cyclohydrolase I, decreased cellular 6R-BH4 content and viable cell number. The inhibiting effects of DAHP were restored by exogenous 6R-BH4. NOS activity, as estimated by nitrite concentrations in the medium, was unchanged by DAHP. Hypoxanthine and xanthine oxidase, which produce superoxide, mimicked the cell-protecting effect of 6R-BH4 which is reported to generate superoxide during its autoxidation. These results suggest that 6R-BH4 acts as a self-protecting factor for NO toxicity with generation of superoxide in NO-producing neurons.
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PMID:Self-protection of PC12 cells by 6R-tetrahydrobiopterin from nitric oxide toxicity. 984 57

We studied the effects of reactive oxygen species (ROS) on intracellular Ca2+ concentration ([Ca2+]i) and their possible modulation by nitric oxide (NO) in fura-2-loaded cultured bovine tracheal epithelium. Hypoxanthine (HX) and xanthine oxidase (XO), which generate superoxide anion (O2-) and hydrogen peroxide (H2O2), dose dependently increased [Ca2+]i. The increase in [Ca2+]i was reduced in the presence of superoxide dismutase (SOD, 200 U/mL) and catalase (200 U/mL) by 29% and 43%, respectively. The iron chelator o-phenanthroline and the hydroxyl radical (.OH) scavenger dimethylthiourea (DMTU) more potently inhibited the response of [Ca2+]i. H2O2-derived .OH generated by the Fenton reaction caused a marked [Ca2+]i elevation, but exogenous H2O2 did not. Sodium nitroprusside (100 microM), an NO donor, potentiated HX-XO-induced [Ca2+]i rise by 50%, an effect that was abolished in the presence of SOD or DMTU. These results suggest that .OH formed by interaction of O2- and H2O2 in the presence of iron may play a major role in the HX-XO-induced disruption of airway epithelial Ca2+ homeostasis, and that NO potentiates ROS-induced [Ca2+]i response, presumably by reacting with O2- and producing .OH.
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PMID:Effects of reactive oxygen species on intracellular calcium in bovine tracheal epithelium: modulation by nitric oxide. 1091 32

Fabrication and characterization of miniaturized amperometric hypoxanthine biosensors are described and demonstrated for monitoring hypoxanthine in myocardial cell culture media. The sensors are based on xanthine oxidase (XO) immobilized on carbon fiber microelectrodes (CFMEs) using a composite film of Nafion and electropolymerized phenol (PPh). Nafion was used for XO immobilization because of its film hydrophobicity, enzyme-favored environment, and electrostatic interaction with XO, which was dispersed in Nafion film by immersing the Nafion-coated CFMEs in XO solution for 5 h. PPh film was formed as an overlay on Nafion and XO-modified CFMEs via electropolymerization. Hypoxanthine was measured with the sensor by the oxidation of enzymatic reaction products, hydrogen peroxide (H(2)O(2)), and uric acid (UA) at +0.60 V (vs Ag/AgCl). The use of Nafion and PPh as a matrix for XO immobilization yields enhanced specificity, sensitivity, and linearity toward hypoxanthine. A dynamic linear range of 5.0 microM to 1.8 mM was achieved with a calculated detection limit of 1.5 microM (S/N = 3) and a sensitivity of 3.144 nA/mM. In addition, the measurement was virtually interference-free from easily oxidizable species such as UA, ascorbic acid, physiological levels of neurotransmitters, and their principal metabolites. The biosensor was used to monitor hypoxanthine accumulation in myocardial cell culture media, in which the level of extracellular hypoxanthine was found to increase with ischemic tolerance.
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PMID:Miniaturized amperometric biosensor based on xanthine oxidase for monitoring hypoxanthine in cell culture media. 1131 22

It has been shown recently that African catfish (Clarias gariepinus) spermatozoa possess relatively low ATP content and low adenylate energy charge (AEC). One of the possible explanations for this phenomenon is that the spermatozoa actively catabolize adenine nucleotides. A relatively high rate of such catabolism could then contribute to the low ATP concentration and low adenylate energy charge observed in the spermatozoa in vitro. To check this hypothesis, we investigated ATP content and adenine nucleotide catabolism in African catfish spermatozoa stored at 4 degrees C in the presence of glycine as an energetic substrate. Our results indicate that the storage of African catfish sperm at 4 degrees C in the presence of glycine causes time-dependent ATP depletion. In contrast to ATP, the AMP content increases significantly during the same period of sperm storage, while the ADP increases only slightly. Moreover, a significant increase of inosine and hypoxanthine content was also found. Hypoxanthine was accumulated in the storage medium, but xanthine was found neither in spermatozoa nor in the storage medium. It indicates that hypoxanthine is not converted to xanthine, probably due to lack of xanthine oxidase activity in catfish spermatozoa. Present results suggest that adenine nucleotides may be converted to hypoxanthine according to the following pathway: ATP-->ADP-->AMP (adenosine/IMP)-->inosine-->hypoxanthine. Moreover, hypoxanthine seems to be the end product of adenine nucleotide catabolism in African catfish spermatozoa. In conclusion, our results suggest that a relatively high rate of adenine nucleotide catabolism contributes to the low ATP concentration and low adenylate energy charge observed in African catfish spermatozoa in vitro.
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PMID:In vitro adenine nucleotide catabolism in African catfish spermatozoa. 1532 39

Hydroxylamine (HA) is a putative intermediate in the conversion of l-arginine to nitric oxide (NO). HA was reported to cause the relaxation of precontracted aorta strips; however, the ionic mechanisms of HA-induced vasorelaxation were not yet known. In the present study, the whole-cell patch-clamp technique was used to examine the effects of HA on ATP-sensitive K+ (K(ATP)) currents and membrane potentials in vascular smooth muscle cells from rat mesenteric arteries and underlying mechanisms. It was found that bath-applied HA reversibly enhanced K(ATP) currents in a concentration-dependent fashion with an EC50 of 54 +/- 3.4 microM and hyperpolarized the cell membrane from -48 +/- 5.2 to -65 +/- 7.5 mV (n = 6, p < 0.01). The increase in K(ATP) currents induced by HA was suppressed by superoxide dismutase (-380 +/- 45 to -160 +/- 20 pA, n = 4, p < 0.01) and N-acetyl-L-cysteine (-385 +/- 55 to -150 +/- 16 pA, n = 5, p < 0.01), indicating the involvement of different free radicals, including superoxide anion. Hypoxanthine/xanthine oxidase increased not only basal K(ATP) currents, but also HA-enhanced K(ATP) currents (from -355 +/- 40 to -480 +/- 62 pA, n = 6, p < 0.05). Sodium nitroprusside, a spontaneous NO donor, and a membrane-permeable cGMP analog (8-bromo-cGMP) were without effects on HA-enhanced K(ATP) currents or basal K(ATP) currents. Our results indicate that HA augmented K(ATP) channel activity and hyperpolarized cell membrane, possibly via increased free radical generation.
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PMID:The effect of hydroxylamine on KATP channels in vascular smooth muscle and underlying mechanisms. 1571 63

Carbon-based screen-printed electrodes are suitable for uric acid detection. Xanthine oxidase (XO) was immobilized either directly on the surface of the electrode or in a reactor with CPG aminopropylsilane in a FIA assembly. Higher reproducibility and lifetime was obtained with the reactor. Optimum conditions were found for the determination of Hypoxanthine (Hx), Inosine (HxR) and Inosine monophosphate (IMP). Calibration curves for IMP, HxR and Hx are linear up to 50 muM with detection limit of 1 muM for 50 mul injection. One assay is completed within 30 s. The reproducibility of 20 muM of Hx was obtained with CV 2%.
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PMID:Amperometric detection of uric acid and hypoxanthine with Xanthine oxidase immobilized and carbon based screen-printed electrode. Application for fish freshness determination. 1896 65

A continuous system for the determination of fish freshness with double enzyme reactors was developed and applied to the determination of the freshness indicator K [Formula: see text] where IMP, HxR and Hx are Inosine monophosphate, Inosine and Hypoxanthine, respectively. The system was assembled with a three electrode screen-printed element (graphite as working electrode, silver as counter and silver, silver chloride as reference electrode) placed in a flow cell, a sample injection valve and two enzyme reactors. The determination of the total amount of HxR and Hx is realized by flowing the sample through two reactors in series: one reactor was packed with nucleoside phosphorylase (Np) and the other with xanthine oxidase (XO) immobilized on aminopropyl glass. Similarly, the other term of the equation was evaluated by flowing through the two reactors the sample treated by Alkaline phosphatase (AlP) for 5-10 min at 45 degrees C. One assay could be completed within 5 min. The system for the determination of fish freshness was reproducible within 2-3% (n=4). The immobilized enzymes were fairly stable for at least 3 months at 4 degrees C. More than 200-300 samples could be analyzed in about one month by using these enzyme reactors provided the disposable screen-printed electrode should be changed every 30-40 real samples. The results obtained suggest that the proposed sensor system provides a simple, rapid and economical method for the determination of fish freshness (K). We applied the present system with two reactors for the determination of K values in fish samples and compared the results with those obtained by the XO-reactor. Correlation factor and regression line between the two methods were 0.992 and Y=-3.14+1.03X respectively. We concluded that the present flow injection analysis (FIA) system with XO and Np reactors was suitable as a simple, easy to handle and reliable instrument for quality control in the fish industry.
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PMID:Development of a system with enzyme reactors for the determination of fish freshness. 1896 33


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