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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Localization of the activity of both the dehydrogenase and oxidase forms of xanthine oxidoreductase were studied in biopsy and postmortem specimens of various human tissues with a recently developed histochemical method using unfixed cryostat sections, poly-(vinyl alcohol) as tissue stabilizator, 1-methoxyphenazine methosulphate as intermediate electron acceptor and Tetranitro BT as final electron acceptor. High enzyme activity was found only in the liver and jejunum, whereas all the other organs studied showed no activity. In the liver, enzyme activity was found in sinusoidal cells and both in periportal and pericentral hepatocytes. In the jejunum, enterocytes and goblet cells, as well as the lamina propria beneath the basement membrane showed activity. The oxidase activity and total dehydrogenase and oxidase activity of xanthine oxidoreductase, as determined biochemically, were found in the liver and jejunum, but not in the kidney and spleen. This confirmed the histochemical results for these organs. Autolytic rat livers several hours after death were studied to exclude artefacts due to postmortem changes in the human material. These showed loss of activity both histochemically and biochemically. However, the percentage activity of xanthine oxidase did not change significantly in these livers compared with controls. The findings are discussed with respect to the possible function of the enzyme. Furthermore, the low conversion rate of xanthine dehydrogenase into xanthine oxidase during autolysis is discussed in relation to ischemia-reperfusion injury.
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PMID:Distribution of xanthine oxidoreductase activity in human tissues--a histochemical and biochemical study. 136 18

Xanthine oxidase is the pathological form of xanthine oxidoreductase, which generates free oxygen radicals, when it converts (hypo)xanthine to urate. We studied 1. developmental changes in rat heart, 2. urate production in catheterized patients, and 3. species differences of cardiac xanthine oxidase. First, we measured the activity of the enzyme at various ages. In rat-heart homogenate, xanthine oxidoreductase increased from 0.5 mU/g (newborn) to 25 mU/g (15 weeks, P less than 0.001). In the second part of the study, we demonstrated that patients undergoing coronary angioplasty showed some cardiac urate production. In the last part of our investigations we showed that in explanted human hearts perfused with hypoxanthine, the enzymatic activity was low, contrasting findings in some other species. The apparent xanthine oxidoreductase activity (mU/g) was: 33 (mouse), 28 (rat), 14 (guinea pig), 0.59 (rabbit), less than 0.1 (pig), 0.31 (man) and 3.7 (cow). We conclude that in several species, cardiac damage due to xanthine oxidase cannot be excluded; however in man it is unlikely to occur.
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PMID:Does xanthine oxidase cause damage during myocardial ischemia? 202 65

Oxygen free radicals generated by xanthine oxidase have been implicated in cardiac damage. The activity of xanthine oxidase/reductase in adult rat heart is considerable. Its assay gives controversial results for other species, for example, rabbits and humans. Therefore, we perfused isolated hearts of various species, including explanted human hearts, to measure the conversion of exogenous hypoxanthine to xanthine and urate. We assayed these purines with high-performance liquid chromatography. The apparent xanthine oxidoreductase activities, calculated as release of xanthine plus 2x urate, were (milliunits per gram wet weight, mean +/- SEM) mice 33 +/- 3 (n = 5), rats 28.5 +/- 1.4 (n = 9), guinea pigs 14.4 +/- 1.0 (n = 5), rabbits 0.59 +/- 0.09 (n = 5), pigs less than 0.1 (n = 6), humans 0.31 +/- 0.04 (n = 7), and cows 3.7 +/- 0.8 (n = 4). In rabbit heart the conversion of hypoxanthine to xanthine was slow, and that of xanthine to urate was even slower. On the other hand, guinea pig and human heart released little xanthine, indicating that xanthine breakdown exceeds its formation. We conclude that isolated perfused mouse, rat, guinea pig, and also bovine hearts show considerable xanthine oxidoreductase activity, contrasting rabbit, porcine, and diseased human hearts.
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PMID:Xanthine oxidoreductase activity in perfused hearts of various species, including humans. 239 79

Xanthine:acceptor oxidoreductase activities were assayed in free skin flaps following prolonged preservation. In normal rat skin, xanthine dehydrogenase transfers electrons to NAD+ and accounts for 73% of total oxidoreductase activity, and xanthine oxidase transfers electrons to molecular oxygen and accounts for the remaining 27%. Xanthine oxidase activity increased significantly in skin flaps during ischemia: approximately 30 and 100% increases after 6 and 24 hr of ischemia, respectively. Allopurinol inhibited xanthine oxidoreductase activity: free skin flaps obtained from allopurinol-treated animals exhibited a low level of xanthine oxidoreductase activity throughout the period of preservation. Systemic allopurinol significantly improved the survival rate from 32 to 75% of free flaps transferred after 24 hr of preservation at room temperature. These observations suggest that the xanthine oxidase system is a major source of oxygen free radicals following ischemia/reperfusion in skin. The increase in xanthine oxidase is attributable to the conversion of xanthine dehydrogenase to oxidase, a conversion which involves sulfhydryl oxidation in skin flaps.
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PMID:Xanthine:acceptor oxidoreductase activities in ischemic rat skin flaps. 264 73

Since only little xanthine oxidase (XO) activity in mammalian brain was detected in earlier reports, the major end product of AMP degradation in the brain has been believed to be hypoxanthine. Our recent experimental study however, has indicated the presence of uric acid in the rat brain subjected to focal ischemia or cold injury. Allopurinol, a xanthine oxidoreductase inhibitor, has been found to markedly suppress the uric acid production in the same experimental settings. These results suggested that uric acid is generated from hypoxanthine by enzymatic reaction in injured brain tissue. The aim of this experiment is to prove the existence of xanthine oxidoreductase activity in brain tissue. Xanthine oxidoreductase activity in rat cerebral tissue was measured immediately or at 24-hour after decapitation. Under pentobarbital anesthesia, twenty Sprague-Dawley rats were killed by decapitation following washout of the blood by trans-cardiac perfusion with cold physiological saline. Immediately or after 24 hours of decapitation ischemia, the forebrain was removed and homogenized in 6 ml ice cold 0.05 M potassium phosphate buffer (pH 7.8) containing 1 mM phenylmethylsulfonyl fluoride, 0.3 mM EGTA, and 10 mM dithiothreitol. The homogenate was centrifuged at 100,000 g for 60 min and then the supernatant was dialyzed overnight against 0.05 M potassium phosphate buffer (pH 7.8). Aliquot of each dialyzed supernatant (sample) and standard xanthine solution with NAD was reacted at 37 degrees C for 15 min to measure the combined activity of xanthine dehydrogenase (XDH) and XO. For the measurement of XO, standard xanthine solution without NAD was used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Xanthine oxidoreductase activity in rat brain tissue: the changes after decapitation]. 280 24

In the hypoxic liver an increased rate of cytosolic and peroxisomal H2O2 generation is due to the accelerated purine nucleotide degradation. The relative contribution of the oxidase type of xanthine oxidoreductase activity increases in hypoxia by less than 10%, the dehydrogenase type of this enzyme is hardly inhibited by the increased concentration of free NADH. Nevertheless, due to the high hypoxanthine supply the xanthine oxidase related H2O2 formation is increased six-fold and together with the peroxisomal uricase-mediated share it accounts for half of the oxygen consumption.
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PMID:H2O2 formation during nucleotide degradation in the hypoxic rat liver: a quantitative approach. 285 Feb 67

Age-dependent differences in the effects of ischemia and reperfusion on ATP breakdown were studied in perfused adult and newborn (10 days old) rat hearts. No-flow ischemia (15 min at 37, 30, or 23 degrees C) was applied and reperfusion (20 min at 37 degrees C) was studied after ischemia at 23 or 37 degrees C. Hypothermia during ischemia protected both age groups to a similar degree against ATP decline, which was linear with temperature. Reperfusion after normothermic ischemia resulted in higher ATP levels in newborn hearts with less release of ATP catabolites (purines). We found no age-related differences in lactate release but large differences in purine release. During normoxia, adult hearts released mainly urate (80% of total) and inosine (7%), but newborns released hypoxanthine (64%) and inosine (15%). Early during reperfusion adult hearts released inosine (58%) and adenosine (18%), but newborns released inosine (53%) and hypoxanthine (38%). These data suggested a lower activity of the potentially deleterious enzyme xanthine oxidoreductase in newborn hearts, which was confirmed by enzymatic assay. ATP-catabolite release during reperfusion was less in newborn than adult hearts, and this coincided with lower xanthine oxidase activity.
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PMID:Different ATP-catabolism in reperfused adult and newborn rat hearts. 316 69

Myocardial xanthine oxidase has been associated with reoxygenation injury induced by oxygen radicals. The damage due to myocardial ischemia and reperfusion increases with age; therefore, one would expect to find more xanthine oxidase in adult than in young hearts. Consequently, we studied the age-dependence of xanthine oxidoreductase activity in hearts, in addition to the localization of the enzyme in cultured rat-heart cells. We measured xanthine oxidase plus dehydrogenase activity in homogenates of hearts and in homogenates of cultured neonatal myocytes and nonmuscular cells. In rat heart homogenates, xanthine oxidoreductase increased from 0.5 +/- 0.1 mU/g wet wt (newborn, mean +/- SD) to 25 +/- 4 mU/g (age 15 weeks, p less than 0.001). The value for adult rabbit heart was more than 1,000 times lower and hardly detectable. Therefore, we did not study young rabbit hearts. In rat myocyte cultures, xanthine oxidoreductase activity increased from 4.2 +/- 1.6 mU/g protein (2nd day of culture) to 17 +/- 4 mU/g (4th day, p less than 0.005). The activity in nonmuscular cells increased much more, from 10.1 +/- 1.1 to 117 +/- 25 mU/g (p less than 0.002). The age-related increase of xanthine oxidoreductase activity in rat heart is in agreement with the implied role in reperfusion damage by the enzyme. Whether myocytes, in which the enzyme has a low activity, could be damaged in this way, remains to be studied.
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PMID:Age-dependent increase in xanthine oxidoreductase differs in various heart cell types. 347 38

Previous work in several laboratories has shown that enzymatic reduction of nitroheterocyclic compounds to reactive but uncharacterized metabolites that damage DNA constitutes an important "activation" step in both bacteria and hypoxic mammalian cells. However, since the known mammalian enzymes having nitroreductase activity are reported to be strongly inhibited by molecular oxygen, the relation of reductive activation to the toxic and mutagenic effects of nitroheterocyclic compounds in intact animals or aerobic cultured cells is unclear. We report here that the process of net nitroreduction of 5-nitro-2-furaldehyde semicarbazone (nitrofurazone) by rat liver xanthine dehydrogenase was considerably less sensitive to inhibition by oxygen than was nitroreduction catalyzed by rat liver or milk xanthine oxidase. The dehydrogenase is the native form of xanthine oxidoreductase and is known to change to the oxidase form as liver extracts are aged or treated with various agents. Incubation at 65 degrees rapidly converted the dehydrogenase form to the oxidase form with concomitant loss of aerobic nitroreductase activity. Similarly, much of the aerobic nitroreductase activity was lost when the preparation was treated with p-hydroxymercuribenzoate but was regained upon subsequent treatment with dithiothreitol. Intermediates generated in the aerobic nitroreduction process bound tightly and probably covalently to protein. Thus, it is possible that aerobic reduction of nitrofurans and other nitroheterocyclic and nitroaromatic components by xanthine dehydrogenase may constitute a significant "activation" process which contributes to the toxic action of such agents.
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PMID:Aerobic reduction of 5-nitro-2-furaldehyde semicarbazone by rat liver xanthine dehydrogenase. 658 3

Oxygen radicals have been proposed to be involved in the induction of liver cell damage during reperfusion after ischemia. The role of xanthine oxidase in this process and the potential of the antioxidant system have been studied in a model of in vivo ischemia of rat liver followed by 1 h reperfusion by the use of enzyme histochemistry. Based on decreased lactate dehydrogenase activity in certain areas of liver parenchyma, cell damage could already be detected at 1 h reperfusion after ischemia. Incubations performed on serial sections showed that the same areas contained decreased activities of xanthine oxidoreductase, xanthine oxidase, catalase and glucose-6-phosphate dehydrogenase. Some individual cells in the undamaged liver parenchyma expressed a very high glucose-6-phosphate dehydrogenase, which suggests that these cells have a good defence against oxidative stress. It is concluded that oxygen radicals derived from xanthine oxidase do not play a decisive role in the induction of cell damage immediately at reperfusion after ischemia. However, it cannot be excluded that xanthine oxidase present in the blood stream can give rise to the development of additional damage later on.
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PMID:The role of xanthine oxidase in ischemia/reperfusion damage of rat liver. 775 31


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