Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.17.1.4 (xanthine dehydrogenase)
1,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irreversible transformation of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) during ischemia was determined measuring XDH and total enzyme activity in kidneys before and after 60 min of clamp of the renal pedicle. Tissue levels of adenine nucleotides, xanthine and hypoxanthine were used as indicators of ischemia. After 60 min of clamping, ATP levels decreased by 72% with respect to controls whereas xanthine and hypoxanthine progressively reached tissue concentrations of 732 +/- 49 and 979 +/- 15 nmol.g tissue-1, respectively. Both total and XDH activities in ischemic kidneys (30 +/- 15 and 19 +/- 1 nmol.min-1.g tissue-1) were significantly lower than in controls when expressed on a tissue weight basis. The fraction of enzyme in the XDH form was however unchanged indicating that the reduction of the nucleotide pool is not accompanied by induction of the type-O activity of xanthine oxidase.
...
PMID:Lack of conversion of xanthine dehydrogenase to xanthine oxidase during warm renal ischemia. 225 87

Xanthine oxidase (XO) has been implicated as a source of free radicals mediating ischemia-reperfusion injury. Conversion of the non-free radical generating xanthine dehydrogenase (XD) to the free radical producing XO during ischemia has been demonstrated in several tissues. We examined the irreversible conversion of XD to XO in the dog brain after ischemia and after ischemia and reperfusion. Under pentobarbital sodium anesthesia and by use of a cerebrospinal fluid compression model of global cerebral ischemia, dogs were subjected to 30 min of ischemia (n = 8) or 30 min of ischemia and 60 min of reperfusion (n = 8). A cerebral perfusion pressure of 60 mmHg was maintained during reperfusion. Eight control dogs were not subjected to ischemia. After the dogs were killed their brains were rapidly removed and frozen in liquid nitrogen. XO and XD + XO activities were measured with a radioassay utilizing 8-[14C]hypoxanthine and separating substrate and products by thin-layer chromatography. Total XD + XO activity was significantly (P less than 0.05) decreased after ischemia and reperfusion (35.6 +/- 8.0 vs. 60.8 +/- 20.8 nmol.min-1.g protein-1 in controls, means +/- SD) but not after ischemia alone (48.2 +/- 20.4). XO/(XD + XO) was approximately 20% in all three groups. Irreversible XD to XO conversion is not an important mechanism leading to early tissue injury in global cerebral ischemia.
...
PMID:No conversion of xanthine dehydrogenase to oxidase in canine cerebral ischemia. 226 Jun 92

Cardiac mitochondrial function as measured by oxidative phosphorylation is impaired by ischemia; and, this deteriorates even further on reperfusion of the heart. Free oxygen radicals, especially the formation of hydroxyl radicals via the iron-catalyzed Haber-Weiss and Fenton reactions have been implicated in the reperfusion injury. In this study, the effect of desferrioxamine (desferal) in the perfusate on mitochondrial function of isolated rat hearts during different periods of normothermic ischemic cardiac arrest (NICA), and subsequent reperfusion was investigated. Mitochondrial functions measured were the QO2 (state 3); ADP/O ratio and oxidative phosphorylation; the mitochondrial, loosely bound (chelateable) iron (LB-iron); the xanthine dehydrogenase and xanthine oxidase activities. Inclusion of desferal in the perfusion solution significantly improved mitochondrial function during the different NICA periods, and prevented the deterioration of mitochondrial function resulting from reperfusion. Desferal did not significantly affect the LB-iron content of the mitochondria or the ratio of xanthine dehydrogenase/xanthine oxidase activities in the mitochondria during NICA or reperfusion. Our experiments suggest that iron, which is free to be chelated by desferal, plays a role in this injury to the rat myocardium.
...
PMID:The effect of desferal on rat heart mitochondrial function, iron content, and xanthine dehydrogenase/oxidase conversion during ischemia-reperfusion. 228 9

The conversion rates of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) were compared with the time course of in vivo lipid peroxidation (LPO) in an ischemia-reperfusion model of acute renal failure in the rat. LPO, measured as the renal release of malondialdehyde (MDA), was found to be markedly elevated only during the first 5 min of blood reflow following a 45-min interval of ischemia (arteriovenous MDA difference -277.3 +/- 53.5 vs. 3.7 +/- 5.7 nmol/l in controls, n = 14). After 30 min of reperfusion, arteriovenous MDA differences nearly reached control values (9.7 +/- 31.8 nmol/l, n = 7). In contrast to enhanced LPO, no significant conversion of XDH to XO was found (XO activity in controls: 23 +/- 1% of XO plus XDH activity vs. 26 +/- 3% after 45 min of ischemia, n = 7). Therefore XO-derived superoxide anion radicals cannot be considered causative for LPO in the reperfusion interval of experimental ischemic acute renal failure.
...
PMID:Xanthine oxidase: evidence against a causative role in renal reperfusion injury. 230 86

We evaluated effluent blood from extremities of human patients undergoing reconstructive surgical treatment, which is routinely accompanied by upper-extremity exsanguination and application of a tourniquet, resulting in total interruption of arterial blood flow to one upper extremity. After tourniquet release (reperfusion), there were immediate increases in the plasma levels of xanthine oxidase activity, uric acid, and histamine in the ipsilateral limb and much smaller increases, if any, in levels of the same materials in plasma obtained from the contralateral extremity. There was no detectable xanthine dehydrogenase activity in plasma from either limb. Plasma also contained evidence of products consistent with the formation of oxygen-derived free radicals, namely, the appearance predominantly in the reperfused limb of hemoglobin and fluorescent compounds. These data indicate for the first time in humans that ischemia-reperfusion events are associated with the appearance of xanthine oxidase activity and its products in the plasma effluent.
...
PMID:Ischemia-reperfusion in humans. Appearance of xanthine oxidase activity. 231 21

Reactive oxygen metabolites generated from the enzyme xanthine oxidase (XO) play an important role in the pathogenesis of ischemia-induced tissue injury. The observation that intracellular proteins such as aspartate transaminase (AST) and alcohol dehydrogenase (ADH) are released from the ischemic liver during reperfusion led us to postulate that XO could be released into the systemic circulation. Livers from fasted rats were extirpated, perfused with oxygenated Krebs-Henseleit buffer, and subjected to 2 h ischemia followed by 2 h reperfusion. Reperfusion increased AST in the perfusate from 1 +/- 1 to 830 +/- 280 U/l, whereas ADH increased from 0.3 +/- 0.1 to 95 +/- 26 U/l. Concomitantly, xanthine dehydrogenase (XDH) + XO activity in the perfusate increased from 0 to 4.1 +/- 1.0 mU/ml. A 64% decrease in endogenous tissue XDH + XO activity paralleled release of XDH + XO. The XDH + XO activity predicted to appear in the circulation after hepatic ischemia was sufficient, when supplied with substrate, to produce severe vascular endothelial injury in vitro, even in the presence of serum or whole blood. These results suggest that massive quantities of XDH and XO are released into the circulation after hepatic ischemia and that the resulting reactive oxygen metabolites could produce widespread tissue injury.
...
PMID:Circulating xanthine oxidase: potential mediator of ischemic injury. 233 69

Prolonged ischemia to skeletal muscle as occurs after an acute arterial occlusion results in alterations in adenine nucleotide metabolism. Adenosine triphosphate continues to be used for cellular functions, and an ischemia-induced degradation of phosphorylated adenine nucleotides is initiated. In this experiment we demonstrated the time-dependent aspect of adenine nucleotide depletion during ischemia and the production of large quantities of soluble precursors. In addition, we studied the rate of conversion of xanthine dehydrogenase to xanthine oxidase, a potential source of oxygen-free radicals, after controlled periods of total normothermic ischemia (4 hours and 5 hours) and during the reperfusion phase. During ischemia complete depletion of creatine phosphate occurred in both groups, and adenosine triphosphate fell from 22.1 +/- 1.3 to 10.3 +/- 1.4 mumol/gm dry weight after 4 hours and from 21.6 +/- 0.7 to 3.9 +/- 0.8 mumol/gm dry weight after 5 hours (p less than 0.05). During reperfusion, creatine phosphokinase resynthesis occurred in both groups, but adenosine triphosphate levels were not significantly increased (p greater than 0.05). A washout of lipid soluble products of adenine nucleotide metabolism occurred equally in both groups. The relationship between phosphorylated adenine nucleotides as measured by the energy charge potential fell significantly in both groups (p less than 0.05), but after the shorter period of ischemia (4 hours it returned to normal during early reperfusion but did not after 5 hours of ischemia. There was 21% +/- 4% necrosis after 4 hours and 51% +/- 8% after 5 hours of ischemic stress when assessed at 48 hours. In conclusion, the degree of adenine nucleotide degeneration as determined primarily by the length of the ischemic period, may be the most important determinant of the ultimate extent of skeletal muscle ischemic necrosis that results from an acute interruption of circulation.
...
PMID:The effect of ischemia/reperfusion on adenine nucleotide metabolism and xanthine oxidase production in skeletal muscle. 237 59

Recently, oxygen free radicals have appeared to play a major role in injury after ischemia, especially that followed by normoxic reperfusion. To clarify the mechanisms of reperfusion injury, the activities of both oxygen radical producing enzymes and radical scavenging enzymes were measured in the ischemic rat kidney followed by reperfusion. All defensive enzymes activities significantly decreased; superoxide dismutase 2.15 +/- 0.14----1.71 +/- 0.11, catalase 186.6 +/- 12.7----116.5 +/- 7.1, glutathione peroxidase 30.0 +/- 2.6----19.1 +/- 2.9, glutathione reductase 118 +/- 5.1----39.9 +/- 6.8 (U/mg protein). Conversion from xanthine dehydrogenase to xanthine oxidase was only 12% of total activity, and all of them were reversible type oxidase. However, it was suggested by the electron spin resonance method that the tissue xanthine oxidase freed of superoxide dismutase could produce oxygen free radicals. In conclusion, reperfusion injury is caused not only by the increase of oxygen free radicals but by the destruction of scavenging systems.
...
PMID:[Mechanisms of reperfusion injury of rat kidney]. 237 11

The purposes of this study were to determine whether exercise training induces increases in skeletal muscle antioxidant enzymes and to further characterize the relationship between oxidative capacity and antioxidant enzyme levels in skeletal muscle. Male Sprague-Dawley rats were exercise trained (ET) on a treadmill 2 h/day at 32 m/min (8% incline) 5 days/wk or were cage confined (sedentary control, S) for 12 wk. In both S and ET rats, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were directly correlated with the percentages of oxidative fibers in the six skeletal muscle samples studied. Muscles of ET rats had increased oxidative capacity and increased GPX activity compared with the same muscles of S rats. However, SOD activities were not different between ET and S rats, but CAT activities were lower in skeletal muscles of ET rats than in S rats. Exposure to 60 min of ischemia and 60 min of reperfusion (I/R) resulted in decreased GPX and increased CAT activities but had little or no effect on SOD activities in muscles from both S and ET rats. The I/R-induced increase in CAT activity was greater in muscles of ET than in muscles of S rats. Xanthine oxidase (XO), xanthine dehydrogenase (XD), and XO + XD activities after I/R were not related to muscle oxidative capacity and were similar in muscles of ET and S rats. It is concluded that although antioxidant enzyme activities are related to skeletal muscle oxidative capacity, the effects of exercise training on antioxidant enzymes in skeletal muscle cannot be predicted by measured changes in oxidative capacity.
...
PMID:Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training. 238 14

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.
...
PMID:Hyperoxia and xanthine dehydrogenase/oxidase activities in rat lung and heart. 254 69


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

---