Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of platelet glucose-6-phosphate dehydrogenase (G-6-PD) in mediating the effects of human platelets on oxidant-induced edema in the isolated perfused rabbit lung was investigated using dehydroepiandrosterone, a specific steroidal inhibitor of G-6-PD. Xanthine oxidase (0.003 and 0.012 U/ml) caused lung edema that was attenuated by coinfusion of washed human platelets. Platelets that were incubated with DEA to inhibit G-6-PD activity augmented xanthine oxidase-induced lung edema and pulmonary hypertension at both doses of xanthine oxidase. Infusion of papaverine to maintain stable pulmonary artery (PA) pressures, incubation of G-6-PD-inhibited platelets with acetylsalicylate, or infusion of a thromboxane-prostaglandin endoperoxide receptor site antagonist, SQ 29548, into the lung perfusate prevented augmentation of lung edema and the PA pressor response by G-6-PD-inhibited platelets. It was concluded that antioxidant-intact platelets attenuate oxidant-induced lung edema by preventing increased membrane permeability, and that G-6-PD-inhibited platelets augment lung edema through hydrostatic mechanisms mediated by release of platelet cyclooxygenase products.
J Clin Invest 1989 Sep
PMID:Human platelets modulate edema formation in isolated rabbit lungs. 252 53

Xanthine oxidase activity in the rat brain was measured by means of high-performance liquid chromatography with electrochemical detection of uric acid. Cerebral ischemia was produced by a four-vessel occlusion method. In the control rat, the enzyme activity was 0.87 +/- 0.13 nmol/gm wet weight/min at 25 degrees C (mean +/- standard deviation), of which 92.4% was associated with the nicotinamide adenine dinucleotide (NAD)-dependent dehydrogenase form and only 7.6% with the oxygen-dependent superoxide-producing oxidase form. However, the ratio of the latter form increased to 43.7% after 30 minutes of global ischemia, despite the total xanthine oxidase activity remaining the same. Thus, it was revealed that uric acid can be synthesized in the rat brain and that cerebral ischemia induced the conversion of xanthine oxidase from an NAD-dependent dehydrogenase to an oxygen-dependent superoxide-producing oxidase. Although the xanthine oxidase pathway has been proposed as a source of oxygen-derived free radicals in various ischemic organs other than brain, the results of the present study suggest the involvement of the oxygen free radicals generated from this pathway in the pathogenesis of the ischemic injury of the rat brain.
J Neurosurg 1989 Sep
PMID:Changes in xanthine oxidase in ischemic rat brain. 254 24

Cell injury from hyperoxia is associated with increased formation of superoxide radicals (O2-). One potential source for O2- radicals is the reduction of molecular O2 catalyzed by xanthine oxidase (XO). Physiologically, this reaction occurs at a relatively low rate, because the native form of the enzyme is xanthine dehydrogenase (XD) which produces NADH instead of O2-. Reports of accelerated conversion of XD to XO, and increased formation of O2- formation in ischemia-reperfusion injury, led us to examine whether hyperoxia, which is known to increase O2- radical formation, is associated with increased lung XO activity, and accelerated conversion of XD to XO. We exposed 3-month-old rats either to greater than 98% O2 or room air. After 48 h, we sacrificed the rats and measured XD and XO activities and uric acid contents of the lungs. We also measured the activities of the two enzymes in the heart as a control organ. We found that the activity of XD was not altered significantly by hyperoxia in rat lungs or hearts, but XO activity was markedly lower in the lung, whether expressed per whole organ or per milligram protein, and remained unchanged in the heart. Lung uric acid content was also significantly lower with hyperoxia. The decrease in lung XO activity may reflect inactivation of the enzyme by reactive O2 metabolites, possibly as a negative feedback mechanism. The concomitant decrease in uric acid content suggests either decreased production mediated by XO due to its inactivation or greater utilization of uric acid as an antioxidant. We examined these postulates in vitro using a xanthine/xanthine oxidase system and found that H2O2, but not uric acid, has an inhibitory effect on O2- formation in the system. We therefore conclude that hyperoxia is not associated with increased conversion of XD to XO, and that the exact contribution of XO to hyperoxic lung injury in vivo remains unclear.
Arch Biochem Biophys 1989 Sep
PMID:Hyperoxia and xanthine dehydrogenase/oxidase activities in rat lung and heart. 254 69

As guinea-pig pulmonary macrophages (PM) synthesize the linoleic acid metabolite 9-hydroxy-octadecadienoic acid (9-OH-Lin) under non-stimulated conditions in relatively large quantities, we investigated whether this product has an effect on the macrophage's own phagocytic cell function. 9-OH-Lin, and also its hydroperoxy precursor 9-hydroperoxy-octadecadienoic acid (9-OOH-Lin), influenced the generation of PM chemiluminescence, a measure of the production of reactive oxygen species. The generation of lucigenin-enhanced chemiluminescence by stimulated and non-stimulated PM was inhibited concentration-dependently. Inhibition was observed at concentrations as low as 10 nM. Since 9-OH-Lin and 9-OOH-Lin also inhibited the generation of chemiluminescence by a cell-free enzyme system, i.e. xanthine/xanthine oxidase, the inhibitory effects might represent a scavenging activity towards reactive oxygen species. 9-OH-Lin and 9-OOH-Lin did not influence other phagocytic cell functions, e.g. PM phagocytic capacity, the aggregatory response to the calcium ionophore A23187, or the release of lysosomal enzymes. The effects of 9-OH-Lin and 9-OOH-Lin could be ascribed to the hydroxy and hydroxyperoxy moiety, respectively, as evidenced by lack of effect of the native fatty acid linoleic acid. We conclude that the formation of 9-OH-Lin and 9-OOH-Lin by PM may represent a regulatory mechanism towards the cell's own activity by modulating reactive oxygen species.
Eur J Biochem 1989 Sep 01
PMID:Modulatory activity of 9-hydroxy- and 9-hydroperoxy-octadecadienoic acid towards reactive oxygen species from guinea-pig pulmonary macrophages. 255 Feb 27

Free radical formation was studied with electron spin resonance during 2 h of intestinal ischemia in the cat, at a blood flow less than 5 ml.min-1.100 g-1, followed by 30-min reperfusion. A modification of the spin trapping technique was used to stabilize highly reactive free radicals. The rate of secondary radical formation was 0.32 +/- 0.06 mumol.min-1.100 g intestine-1 before ischemia and increased to a maximum of 0.66 +/- 0.09 mumol.min-1.100 g-1 during the first minutes of reperfusion (mean +/- SE, n = 5). This could be prevented either by maintaining intestinal blood flow at 8-15 ml.min-1.100 g-1, by administering allopurinol before and during ischemia, or by perfusing the intestinal lumen with an O2-saturated buffer solution during ischemia, resulting in maximum rates of radical production during reperfusion of 0.37 +/- 0.04 (n = 6), 0.33 +/- 0.04 (n = 5), and 0.39 +/- 0.13 mumol.min-1.100 g-1 (n = 5), respectively. The results demonstrate that free radicals are produced in the intestine during reperfusion after a period of reduced blood flow below a certain critical level, and that inhibition of xanthine oxidase and prevention of hypoxia will eliminate this radical production.
Am J Physiol 1989 Sep
PMID:Radical production during in vivo intestinal ischemia and reperfusion in the cat. 255 Nov 84

To understand the involvement of changes in sulfhydryl groups in causing depression of the sarcolemmal Ca2+-pump activities, this study was undertaken to examine the effects of oxygen free radicals on rat heart sarcolemmal sulfhydryl groups, Ca2+-stimulated adenosinetriphosphatase (ATPase), and ATP-dependent Ca2+ accumulation. In addition, the effects of sulfhydryl reagents such as dithiothreitol, cysteine, and N-ethylmaleimide on Ca2+-pump activities were investigated. The inhibition of sarcolemmal Ca2+-pump activities by O2-. (xanthine + xanthine oxidase) and H2O2 was decreased by the addition of dithiothreitol or cysteine in a dose-dependent manner. N-ethylmaleimide also showed inhibitory effects on Ca2+-pump activities both in a dose- and time-dependent manner; dithiothreitol and cysteine prevented changes in Ca2+-pump activities because of N-ethylmaleimide. Heart sarcolemmal sulfhydryl groups were depressed by O2-., H2O2, and .OH (H2O2 + Fe2+) both in a dose- and time-dependent manner. Superoxide dismutase, catalase, and D-mannitol showed protective effects on the sulfhydryl group depression by O2-., H2O2, and .OH, respectively. A significant correlation between changes in sarcolemmal Ca2+-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen. These results indicate that oxygen free radicals may depress the heart sarcolemmal Ca2+-pump activities by modifying the sulfhydryl groups in the sarcolemmal membrane.
Am J Physiol 1989 Sep
PMID:Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals. 255 Nov 90

In view of the importance of Ca2+-channels in controlling the entry of Ca2+ into the myocardium, this study was undertaken to examine the effects of oxygen free radicals on the binding of Ca2+-channel antagonists in rat heart by employing [3H]-nitrendipine as a ligand. Isolated heart membranes were incubated with xanthine + xanthine oxidase (a superoxide anion radicals generating system), hydrogen peroxide (an activated species of oxygen), or hydrogen peroxide + Fe2+ (a hydroxyl radicals generating system). The assay of the [3H]-nitrendipine binding activity revealed that the maximal number of binding sites (Bmax) were reduced in a time-dependent manner by superoxide radicals without any changes in the binding constant (Kd); a significant reduction of Bmax was seen after incubating membranes with xanthine + xanthine oxidase for a 10-min-period. Superoxide dismutase showed a protective effect on the superoxide radicals induced reduction in Bmax. Both hydrogen peroxide and hydroxyl radicals also depressed the Bmax for [3H]-nitrendipine binding without any significant change in Kd; catalase and mannitol showed protective effects on hydrogen peroxide or hydroxyl radicals induced depression in Bmax, respectively. These results indicate that oxygen free radicals may reduce the number of Ca2+-channels in the cell membrane and this change may contribute towards decreasing the voltage-dependent Ca2+ influx in the cardiac cell.
J Mol Cell Cardiol 1989 Sep
PMID:Reduction of calcium channel antagonist binding sites by oxygen free radicals in rat heart. 255 87

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.
Jpn Circ J 1989 Sep
PMID:Possible mechanism responsible for mechanical dysfunction of ischemic myocardium: a role of oxygen free radicals. 255 60

Thirty liver specimens from 30 pre-eclamptic women with and without liver dysfunction were examined for the amount of lipofuscin pigment deposited. The amount of hepatic lipofuscin correlated positively with plasma urate concentrations. This finding may indicate an involvement of oxygen-free radicals and xanthine oxidase in the pathophysiology of pre-eclampsia.
Asia Oceania J Obstet Gynaecol 1989 Sep
PMID:Hepatocellular lipofuscin in pre-eclampsia. 259 92

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.
Farmaco 1989 Sep
PMID:Xanthine oxidase inhibition: effect of an N-alkyl substituent on C-2 of the nucleus of 8-azahypoxanthine. 260 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>