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

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study rat epigastric island flaps were used as a model to investigate selected tissue biochemical changes occurring during secondary ischemia. It was hypothesized that free radical damage, depletion of free radical scavengers, depletion of ATP, and increased edema might explain differences in flap survival between partial (venous obstruction) and total (arteriovenous obstruction) ischemia and decreased flap survival with increasing ischemia time. Flaps were given 2 hr or primary ischemia, 8 hr of normal perfusion, then secondary ischemia of 0, 2, 4, 8, or 12 hr with either arteriovenous obstruction or venous obstruction. Biochemical analysis of the skin was performed after 0, 24, or 96 hr reperfusion. Only minor differences were found between arteriovenous and venous ischemia for any of five biochemical parameters, despite a previous finding that venous ischemic flaps are more susceptible to necrosis. Levels of xanthine oxidase and malonyldialdehyde (both indices of free radical generation) increased with ischemia time. Levels of superoxide dismutase (a free radical scavenger) correspondingly decreased. Tissue levels of ATP decreased after ischemia and recovered to normal for shorter but not for longer ischemia times after 96 hr of reperfusion in parallel with flap survival. Edema increased immediately after the ischemic insult but decreased once the tissue became necrotic. These results imply roles for free radicals, ATP, and edema in secondary ischemia, but do not distinguish between arteriovenous and venous secondary ischemia.
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PMID:The biochemical basis of secondary ischemia. 153 98

Chronic inflammation of the colon and the rectum was induced by intracolonic administration of 25 mg trinitrobenzoic sulfonic acid (TNB) in 0.25 ml 30% ethanol. Three weeks after TNB administration the colon and the rectum showed transmural, granulomatous inflammation which had many similarities to Crohn's disease and furthermore to the morphological and functional changes which occur in early phases of postischemic intestinal damage. In the colon of TNB-treated animals the ATP and GTP levels were markedly decreased. The accumulation of thiobarbituric acid-reactive substances (TBA-RS) demonstrated a free radical-mediated component of the tissue damage. Treatment with oxypurinol radical scavenger and xanthine oxidoreductase inhibitor diminished the morphological changes, the loss of energy-rich nucleotides and the TBA-RS accumulation.
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PMID:Protective influence of oxypurinol on the trinitrobenzene sulfonic acid(TNB) model of inflammatory bowel disease in rats. 157 48

The effect of hypoxia on subsequent susceptibility of porcine pulmonary artery endothelial cells (PAEC) to hydrogen peroxide (H2O2) injury was studied. Preexposure of PAEC to hypoxia for 3 or more h significantly increased susceptibility to subsequent H2O2 challenge. Analysis of the activities of antioxidant enzymes and xanthine oxidase/dehydrogenase suggested that changes in these enzymes in hypoxic PAEC were not responsible for the increased susceptibility. However, hypoxia resulted in significant time-dependent decreases in total glutathione at 12 h or more. The rate of glutathione regeneration in diethylmaleate-treated PAEC and the rate of uptake of cystine and glycine were significantly lower during hypoxia. Hypoxia also caused depletion of ATP and NADPH levels in PAEC, but these did not occur until well after hypoxia-enhanced susceptibility to H2O2 injury was demonstrable. Alterations in glutathione levels and enhanced susceptibility were reversible when hypoxic PAEC were returned to normoxia. These results indicate that hypoxia increased the susceptibility to H2O2 injury by decreasing the ability of PAEC to maintain and regenerate cellular glutathione content in response to H2O2 challenge.
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PMID:Hypoxia increases the susceptibility of pulmonary artery endothelial cells to hydrogen peroxide injury. 157 99

The respective roles of H2O2 and .OH radicals was assessed from the protective effects of catalase and the iron chelator o-phenanthroline on 1) the inhibition of protein synthesis, and 2) DNA damage and the related events (activation of the DNA repairing enzyme poly(ADP)ribose polymerase with the associated depletion of NAD and ATP stores) in cultured endothelial cells exposed to the enzyme reaction hypoxanthine-xanthine oxidase (HX-XO) or pure H2O2. Catalase added in the extracellular phase completely prevented all of these oxidant-induced changes. O-phenanthroline afforded a complete protective effect against DNA strand breakage and the associated activation of the enzyme poly(ADP)ribose polymerase. By contrast, iron chelation was only partially effective in maintaining the cellular NAD and ATP contents, as well as the protein synthetic activity. In addition, the ATP depletion following oxidant injury was much more profound than NAD depletion. These results indicate that: 1) .OH radical was most likely the ultimate O2 species responsible for DNA damage and activation of poly(ADP)ribose polymerase; 2) both H2O2 and .OH radicals were involved in the other cytotoxic effects (inhibition of protein synthesis and reduction of NAD and ATP stores); and 3) NAD and ATP depletion did not result solely from activation of poly(ADP)ribose polymerase, but other mechanisms are likely to be involved. These observations are also compatible with the existence of a compartmentalized intracellular iron pool.
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PMID:Differential protective effects of O-phenanthroline and catalase on H2O2-induced DNA damage and inhibition of protein synthesis in endothelial cells. 166 Apr 79

Hydrogen peroxide produces marked antigonadotropic and lytic actions in luteal cells, but the effects of superoxide, the archetypal oxygen radical, are unknown. Xanthine oxidase generates superoxide, and the activity of this enzyme, and purine substrate, are increased under ischemia, such as that seen at luteal regression. We therefore examined the actions of xanthine oxidase on luteal cells to assess the effects of this enzyme and the superoxide anion on luteal function. Xanthine oxidase, in the presence of hypoxanthine (50 microM), produced marked inhibition of LH-sensitive cAMP and progesterone production with complete inhibition at 25 mU/ml and half-maximal inhibition at about 5 mU/ml. These antigonadotropic actions of xanthine oxidase were rapid with maximal effects within 5 min, followed several minutes later by substantial depletion of ATP. Heat, superoxide dismutase, and catalase or catalase alone abolished the actions of xanthine oxidase. While depletion of ATP by xanthine oxidase was prevented by 3-amino-benzamide, an inhibitor of DNA repair, inhibition of cAMP and progesterone production was still evident. Xanthine oxidase also inhibited progesterone synthesis stimulated by 8-bromo-cAMP. Isobutylmethylxanthine, a cAMP phosphodiesterase inhibitor, did not reverse the inhibition of cAMP accumulation by xanthine oxidase, and the enzyme had no effect on LH receptor binding activity. Since catalase reversed the effects of xanthine oxidase, we conclude that superoxide was rapidly dismuted to hydrogen peroxide and mediated the antigonadotropic and antisteroidogenic actions of xanthine oxidase in luteal cells. The sensitivity of luteal cells to xanthine oxidase raises the possibility that this enzyme may serve as a significant source of hydrogen peroxide in the corpus luteum.
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PMID:Inhibition of gonadotropin action and progesterone synthesis by xanthine oxidase in rat luteal cells. 170 32

Reperfusion after reversible ischemia has been shown to result in prolonged depression of contractile function ("myocardial stunning"). Recent studies suggest that oxygen free radicals may mediate postischemic dysfunction. Since heart sarcolemmal membranes, which contain several types of enzymes, ion channels and receptors play important roles to maintain cell functions, the present study was undertaken to examine the effects of oxygen free radicals on heart sarcolemmal membrane functions in vitro. In the presence of a superoxide anion radical-generating system (2mM xanthine plus 0.03 U/ml xanthine oxidase), sarcolemmal Ca(2+)-stimulated ATPase activity and ATP-dependent Ca2+ accumulation were inhibited in an incubating time-dependent manner. Both lipid peroxidation (r = 0.82) and sulfhydryl group content (r = 0.95) showed significant correlations with Ca(2+)-stimulated ATPase activity. ATP-independent Ca2+ bindings were increased upon treating the membranes with xanthine plus xanthine oxidase. Voltage-dependent Ca(2+)-channels were also affected by oxygen free radicals. The maximal number of binding sites (Bmax) for [3H]-nitrendipine binding was depressed without any changes in dissociation constant (Kd). The effects of oxygen free radicals on adrenergic receptors were more complex. Bmax for [3H]-dihydroalprenolol (DHA) binding (beta-receptor) was increased whereas Bmax for [3H]-prazosin binding [alpha 1-receptor) was decreased after incubating the membrane with xanthine plus xanthine oxidase. Kd for [3H]-DHA or [3H]-prazosin binding was increased. Superoxide dismutase showed protective effects on the changes in these membrane functions due to xanthine plus xanthine oxidase. It is suggested that oxygen free radicals damage heart sarcolemmal membrane functions which may lead to cardiac dysfunction in the stunned myocardium.
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PMID:Stunned myocardium and oxygen free radicals--sarcolemmal membrane damage due to oxygen free radicals. 183 72

The purpose of this study was to better characterize renal adenine nucleotide pool responses to different forms of shock, contrast the changes to those found in other intra-abdominal organs (the liver and small intestine), and assess whether these changes are closely mimicked by those produced by renal arterial occlusion, the usual method used to study ischemic acute renal failure. Rats were subjected to hemorrhagic shock, septic shock, or cardiopulmonary shock of varying severities and durations. The liver consistently had the greatest energy depletion, followed by the kidney, and then the small intestine. However, only the kidney developed clear morphological damage (S3 brush border sloughing). Kidney adenylate pools were better preserved during septic shock and cardiopulmonary shock than during hemorrhagic shock despite comparable blood pressures. Only profound hemorrhagic shock (35-40 mm Hg for 25 minutes) decreased total adenylate pools (ATP + ADP + AMP). However, the degree of renal catabolite (nucleosides plus purine base) accumulation did not correlate with the amount of renal total adenine nucleotide depletion, partially because circulating catabolites contributed to intrarenal catabolite pools. Purine base/uric acid ratios differed among shocked organs, consistent with different degrees of xanthine oxidase activity (small intestine greater than liver greater than kidney). Renal morphological damage decreased during the immediate (0-30 minutes) postshock period, and the extent of this improvement was not altered by xanthine oxidase inhibition (oxypurinol), suggesting that the immediate postshock period is not one of serious oxidative injury. Shock, in comparison with renal arterial occlusion, caused only modest ATP loss/catabolite accumulation, very low purine base/uric acid ratios, and no immediate-reperfusion (0-30 minutes) resynthesis of the total adenylate pool. Thus, ischemia-induced renal adenylate changes may differ considerably, depending on the nature of the ischemic event.
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PMID:Adenine nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury. 198 61

Using a highly specific assay that minimizes enzyme inactivation in vitro, we found that rabbit myocardial tissue contained low levels of xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity that were effectively inhibited by pretreatment of hearts with allopurinol. In parallel, allopurinol treatment also improved ventricular developed pressure, peak systolic pressure, and coronary flow in isolated hearts subjected to 30 min of normothermic global ischemia and 30 min of reperfusion. Although function was protected by allopurinol treatment, creatine kinase (CK) release was not altered by allopurinol. Inhibition of myocardial XO with allopurinol did not increase myocardial ATP or phosphocreatine. In addition, allopurinol did not scavenge superoxide anion or hydrogen peroxide in vitro. The results support the possibility that relatively low amounts of XO activity, similar to levels reported in human myocardium, may contribute to cardiac ischemia-reperfusion injury.
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PMID:Existence and participation of xanthine oxidase in reperfusion injury of ischemic rabbit myocardium. 200 Sep 75

Adenosine and adenine nucleotides shorten the action potential duration of atrial myocytes and activate a specific acetylcholine and adenosine receptor-operated potassium outward current referred to as IKACh,Ado. The objective of this study was to determine whether adenine nucleotides shorten the action potential duration and increase IKACh,Ado in guinea pig atrial myocytes by directly activating adenosine receptors. The potency and efficacy of AMP and adenosine in increasing IKACh,Ado and shortening atrial action potential duration were similar; the EC50 values for AMP and adenosine were 3.4 +/- 0.8 and 3.1 +/- 0.4 microM, respectively. Likewise, the maximum increases in IKACh,Ado caused by AMP and adenosine were similar (122 +/- 11% versus 123 +/- 9%). In comparison, ATP and the stable analogue of AMP, adenosine monophosphorothioate (AMPS), were significantly less potent and efficacious than adenosine and AMP, and adenosine receptor antagonist 8-(p-sulfophenyl)theophylline and abolished in the presence of adenosine deaminase and alpha, beta-methylene-ADP (APCP, an inhibitor of AMP degradation). Binding of the A1-adenosine antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) to guinea pig atrial membranes treated with adenosine deaminase and APCP was reduced up to 60% by 100 microM concentrations of AMP, AMPS, and adenosine. Inosine inhibited binding by 43 +/- 3% at 100 microM, whereas hypoxanthine and xanthine had little (5-10% inhibition) and uric acid had no effect. Only 3% of AMP and 35% of AMPS were recovered intact after a 90-minute incubation at 21 degrees C with preparations of guinea pig atrial membranes. Percent displacement of [3H]DPCPX binding to atrial membranes by 100 microM AMP was significantly less in the presence of nucleoside phosphorylase and xanthine oxidase (to degrade inosine, hypoxanthine, and xanthine to uric acid) than in their absence (12.4 +/- 3.1% versus 49.7 +/- 1.5%). The results suggest that the observed electrophysiological actions of adenine nucleotides in cardiomyocytes are mediated by adenosine and are consistent with activation of A1-adenosine receptors.
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PMID:Electrophysiological and receptor binding studies to assess activation of the cardiac adenosine receptor by adenine nucleotides. 200 6

Profiles of the catabolism of adenine nucleotides in cultured plant cells were investigated. Adenine nucleotides, prelabelled by incubation of suspension-cultured Catharantus roseus cells with [8-14C]adenosine, were catabolized rapidly and most of the radioactivity appeared in 14CO2. Allantoin and allantoic acid, intermediates of the oxidative catabolic pathway of purines, were temporarily labelled. When the cells, prelabelled with [8-14C]adenosine, were incubated with high concentrations of adenosine, the rate of catabolism of adenine nucleotides increased. The results suggest that the relative rate of catabolism of adenine nucleotides is strongly dependent on the concentration of adenine nucleotides in the cells. Studies using allopurinol, coformycin and tiazofurin, inhibitors of enzymes involved in purine metabolism, suggest that participation of AMP deaminase and xanthine oxidoreductase in the catabolism of adenine nucleotides in plant cells. AMP deaminase was found in extracts from C. roseus cells and its activity increased significantly in the presence of ATP. In contrast, no adenosine deaminase or adenine deaminase activity was detected. Qualitative differences in the catabolic activity of AMP were observed between suspension-cultured cells from different species of plants.
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PMID:Catabolism of adenine nucleotides in suspension-cultured plant cells. 201 71


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