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)

It has been proposed that a major target organelles damaged by the ischemic process, probably by the oxygen free radicals generated, is the portion of the excitation-contraction coupling system that regulates Ca2+ delivery (the sarcoplasmic reticulum and sarcolemma) to the contractile proteins. We tested this hypothesis by studying the effect of in vitro generation of oxygen free radicals from xanthine-xanthine oxidase system or dihydroxyfumarate (DHF)/Fe3+-ADP system on Ca2+ flux behavior of canine cardiac sarcoplasmic reticulum (SR); sarcolemmal (Na+, K+)-ATPase and Na+-Ca2+ exchange activities; and myofibrillar (Ca2+, Mg2+)-ATPase activity. Generation of oxygen free radicals by xanthine oxidase acting on xanthine as a substrate increased the passive Ca2+ efflux and decreased intravesicular Ca2+ with no effect on active Ca2+ influx (Ca2+-ATPase) of SR vesicles. Similar exposure of sarcolemmal vesicles to xanthine plus xanthine oxidase stimulated Na+-Ca2+ exchange activity. When sarcolemmal vesicles were incubated with DHF plus Fe3+-ADP, (Na+, K+)-ATPase activity was decreased. It is postulated that the SR Ca2+ efflux pathways but not catalytic activity of the Ca2+ pump and sarcolemmal (Na+, K+)-ATPase involving Na+-Ca2+ exchange activity are altered by oxygen free radicals, and such changes may partly account for the occurrence of intracellular Ca2+ overload during the course of myocardial ischemia. Interestingly, oxygen free radicals from xanthine-xanthine oxidase system had no effect on myofibrillar pCa-ATPase curve. From this set of observations we would hypothesize that the SR and sarcolemma may be the principal target organelles of oxygen free radicals attack in the ischemic injury and not the contractile proteins per se.
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PMID:Possible mechanism responsible for mechanical dysfunction of ischemic myocardium: a role of oxygen free radicals. 255 60

Several new 2-n-alkyl-8-azahypoxanthines were synthesized and tested. The compounds were obtained from 4(5)-amino-5(4)-carbamoyl-1,2, 3-triazole and the suitable ethyl alkanoate in the presence of sodium ethoxide. The inhibitory activity of these compounds against xanthine oxidase was dependent on the length of the alkyl chain of the substituent: 2-n-hexyl-8-azahypoxanthine was the most active product. This fact pointed out the great importance of the weak interaction between the substituent and the adjacent region of the active site of the enzyme.
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PMID:Xanthine oxidase inhibition: effect of an N-alkyl substituent on C-2 of the nucleus of 8-azahypoxanthine. 260 36

Postischemic renal dysfunction (PIRD) is characterized by a reduction in glomerular filtration and tubular reabsorption of solute. The relative contribution of oxygen free radicals (OFRs) generated during reperfusion remains unclear. This study characterized the renal response to OFRs--independent of an ischemic insult. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with a modified Krebs' buffer. Hypoxanthine (25 mumole) and xanthine oxidase (1 unit) were combined and infused proximal to the kidney. There was a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and a 70% reduction in glomerular filtration rate. There was also a significant reduction in urine flow rate and oxygen consumption. The percentage reabsorption of filtered water and sodium by the renal tubules was not diminished, however. This pattern was not observed when the xanthine oxidase was inactivated or when the perfusate was pretreated with superoxide dismutase (250 units/ml) and catalase (500 units/ml). The generation of OFRs, independent of an ischemic insult, causes a decrease in glomerular filtration out of proportion to the decrease in renal flow similar to that observed with PIRD. OFRs may contribute to the hemodynamic and glomerular alterations seen with PIRD. Factors other than OFRs, probably associated with ischemia, must be responsible for the tubular dysfunction.
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PMID:Oxygen free radical mediated renal dysfunction. 271 9

It has been suggested that oxygen-derived free radicals play a decisive role in the pathogenesis of acute experimental pancreatitis in a model of edematous pancreatitis. Accordingly, allopurinol, a xanthine oxidase inhibitor, was shown to mitigate the development of nonfatal acute pancreatitis in ex vivo perfusion models using dogs. For further evaluation of allopurinol, its effect was studied in two forms of fatal necrotizing acute experimental pancreatitis: sodium taurocholate-induced pancreatitis in rats and choline-deficient ethionine-supplemented diet-induced pancreatitis in mice. Allopurinol did not affect the mortality rate, pancreatic enzyme elevation in serum and ascites, the enzyme content of the pancreas, or any parameter indicating histopathological damage in the pancreas. Although these experiments did not determine the role oxygen-derived free radicals play in the development of pancreatitis, they show, none the less, the absence of any beneficial therapeutic effect of a xanthine oxidase like allopurinol on the development of the disease once it has begun.
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PMID:Xanthine oxidase inhibitor in acute experimental pancreatitis in rats and mice. 276 73

The ability of Oxyphenbutazone (a non-steroidal antiinflammatory drug) to react with singlet oxygen and superoxide anions, possible mediators of the damage to the lipids of the cell membranes during inflammation was studied. Oxyphenbutazone inhibited the reduction of nitroblue tetrazolium in aerobic riboflavin-photosensitized oxidation of methionine, but did not influence the cytochrome C-reduction by superoxide-generating system xanthine-xanthine oxidase. Oxyphenbutazone was photooxidized in the presence of Rose Bengal, the latter being a photosensitizer. The increase of the reaction rate of Oxyphenbutazone-oxidation in D2O as compared to H2O, as well as the inhibition of oxidation by singlet oxygen-quencher sodium azide confirmed the participation of singlet oxygen in this process. It was found that Oxyphenbutazone reacted with singlet oxygen, but did not react with superoxide anions. This was supported by the observed protection of erythrocyte membranes from the hemolytic action of the singlet oxygen-generating system Rose Bengal + light.
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PMID:Reactions of oxyphenbutazone with active oxygen species. 282 29

D.c. polarography of 2-amino-6-chloropurine in aqueous medium over a broad pH range revealed two diffusion waves, the first of which corresponds to reduction of the C(6)-Cl bond, leading to formation of 2-aminopurine in high yield. Condensation of the sodium salt of 2-aminopurine with (2-acetoxyethoxy)methyl chloride led to the two isomeric 9- and 7-(2-hydroxyethoxymethyl)-2-aminopurines. The 9- isomer, 6-deoxyacyclovir, a prodrug of acyclovir previously synthesized by another route, was readily converted to the latter by xanthine oxidase; the 7-isomer was not a substrate. The intense fluorescence of 6-deoxyacyclovir makes it a convenient fluorescent substrate for xanthine oxidase, although less sensitive than xanthine; it is shown that 2-aminopurine would be a very sensitive fluorescent substrate. The polarographic behaviour of the riboside of 2-amino-6-chloropurine was virtually identical with that of the parent purine, leading to a simple procedure for conversion of 2-amino-6-chloropurine nucleosides and acyclonucleosides to the corresponding 2-aminopurine congeners.
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PMID:Preparative electrochemical reduction of 2-amino-6-chloropurine and synthesis of 6-deoxyacyclovir, a fluorescent substrate of xanthine oxidase and a prodrug of acyclovir. 283 54

The detergent-induced amplification of lucigenin-dependent chemiluminescence of O2-, generated by xanthine oxidase or microsomal NADPH oxidase was studied. An assay system is described which is at least 10 times more sensitive than normal lucigenin-dependent chemiluminescence due to the amplification by high concentrations of octylphenylpolyethylene glycol (Triton X-100). Compared to the superoxide dismutase-sensitive reduction of acetylated cytochrome c, a 3750-fold lower amount of microsomal protein was necessary to produce an O2- signal 10-fold above the background. In contrast to cytochrome c reduction, detergent-amplified chemiluminescence of lucigenin was completely inhibited by superoxide dismutase and therefore more selective for O2-. The membrane-bound and Triton X-100-solubilized NADPH oxidase from microsomes of macrophages was activated by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid and inhibited by Ca2+ and sodium dodecyl sulfate. The membrane-bound enzyme showed a Km value of 1.35 microM, which decreased to 0.95 microM after the addition of 12% (g/g) Triton X-100. The Km and Vmax values of soluble xanthine oxidase were not influenced by Triton X-100, indicating that the enzyme activities were not impaired by the high concentrations of detergent.
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PMID:Detergent-amplified chemiluminescence of lucigenin for determination of superoxide anion production by NADPH oxidase and xanthine oxidase. 283 20

The effect of superoxide radical on the azide-insensitive ATP-dependent Ca2+-transport by a plasma membrane (PM)-enriched fraction (F2) and an endoplasmic reticulum (ER)-enriched fraction (F3) isolated from pig coronary artery was examined using xanthine oxidase plus xanthine to generate superoxide ions. A preincubation with xanthine oxidase plus xanthine at 37 degrees C preferentially inactivated the oxalate-stimulated Ca2+ uptake by the F3 fraction rather than the phosphate-stimulated uptake by the F2 fraction, indicating that the Ca2+ pump in the ER was more susceptible to this free radical. The inactivation of the Ca2+ uptake depended on the concentrations of xanthine oxidase and xanthine in the preincubation mixture as well as on the preincubation time. Furthermore, the inclusion of superoxide dismutase in the preincubation mixture prevented the inactivation. Thus the inactivation was caused by superoxide radical. Preincubation with xanthine oxidase plus xanthine, however, altered the half-life of efflux of Ca2+ from these vesicles only marginally. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the F3 fraction showed formation of a Ca2+-dependent acid stable phosphoenzyme at 0 degree C predominantly at a protein band corresponding to 100 kDa. The level of the 100-kDa acylphosphate intermediate was inhibited in parallel with the inhibition of the Ca2+ uptake by preincubation with xanthine oxidase plus xanthine. We conclude that superoxide radical inactivates the ER Ca2+ transport by lowering the level of the phosphoenzyme.
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PMID:Effect of superoxide radical on Ca2+ pumps of coronary artery. 284 93

The protective effects of various tannins on ocular lens against the induced oxidative damage were examined. Oxidative damage on mouse lenses was induced by incubating them with xanthine-xanthine oxidase, ADP and Fe3+ (X.XOD system). X.XOD system caused an increase in lipid peroxide of lens membrane and decreases in Na,K-ATPase and GSH reductase activities in the lenses. After pretreatment of lenses with X.XOD system, the lenses were incubated with tannins in the medium containing no X.XOD system and the effects of tannins on biochemical parameters in the lenses were determined. Higher molecular tannins (penta-O-galloyl-beta-D-glucopyranose and geraniin) decreased the lipid peroxide in the lens and restored GSH content, Na,K-ATPase and GSH reductase activities in the lens to the level comparable to control. However, all of tannins tested restored much insufficiently the cation level (ratio of Na+/K+) in the lens regardless of extents of restoration of Na,K-ATPase level by them. Because it was supposed that tannins might act primarily on the plasma membrane, the effect of tannins on lens plasma membrane was examined using cell free system. Lens was homogenated and separated into membrane pellet and supernatant. When the pellet was treated with X.XOD system, the lipid peroxide in the pellet increased and its Na,K-ATPase activity decreased. In addition, the treated pellet decreased the GSH level and GSH reductase activity in the supernatant, when the pellet was combined with the supernatant. Higher molecular tannins reduced lipid peroxide content in the X.XOD-treated pellet to control level and the pellet in which lipid peroxide content was reduced by tannins caused much less decreases of GSH level and GSH reductase activity in the supernatant. These results suggest that, in intact lens, higher molecular tannins act on plasma membrane to eliminate lipid peroxide produced by the X.XOD system and consequently suppress the decreases in both Na,K-ATPase and GSH reductase activities without their entering inside the cell.
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PMID:Effects of tannins on the oxidative damage of mouse ocular lens. I. Using the oxidative damage model induced by the xanthine-xanthine oxidase system. 284 23

The generation of superoxide radicals from xanthine oxidase-hypoxanthine in a particulate fraction of gerbil cerebral cortex influenced the activity of the synaptic enzyme adenylate cyclase, as well as Mn2+- and Na+,K+-sensitive forms of ATPase. Low concentrations of xanthine oxidase actually elevated the sensitivity of adenylate cyclase to GTP, GTP + norepinephrine (NE), and forskolin but not significantly to Mn2+. Higher levels of xanthine oxidase elicited a marked inhibition of these responses. The stimulation of adenylate cyclase mechanisms requiring GTP (GTP, forskolin, and NE) was more susceptible than was Mn2+, suggesting that the guanine nucleotide stimulatory protein was more vulnerable to free radical attack than the catalytic site of adenylate cyclase. Superoxide dismutase (SOD), but not catalase, partially protected the forskolin-sensitive enzyme from the action of xanthine oxidase-hypoxanthine. A combination of SOD plus catalase preserved enzyme responses to forskolin. In comparison, additions of SOD plus mannitol or catalase plus flunarizine were less effective. The sensitivity of the particulate ATPase to Mn2+ was more labile to the consequence of superoxide formation than Na+, K+ -ATPase. In this regard the Ca2+,Mg2+ sensitivity of the enzyme was reduced only to a marginal extent. The findings might be analogous to in vivo data in which cerebral adenylate cyclase and Na+, K+-ATPase are damaged following postischemic reperfusion in gerbils, a process thought to be mediated by free radicals.
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PMID:Free radicals generated by xanthine oxidase-hypoxanthine damage adenylate cyclase and ATPase in gerbil cerebral cortex. 285 Apr 58


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