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)

A study was made of the metabolism by the rabbit of adenine administered intravenously at a dose of 35 mg/kg with 100 micronCi of 8-14C-adenine. The infused adenine was removed from the blood in two phases, first by diffusion into the tissues and second by metabolic reactions throughout the body. The adenine equilibrated within a few seconds equally between plasma and red blood cells and between them and kidney, liver, duodenum, lung and heart. Diffusion into skeletal muscle was much slower and into brain slowest. The more gradual disappearance of adenine from blood, and from the rest of the body, with a half-life of about 20 minutes and with complete removal by two hours, was predominantly along three pathways, leading to, after four hours: 1) 74 per cent in adenine nucleotide (mostly AMP, ADP, and (ATP); 2) 12 per cent as unchanged adenine in the urine; and 3) 11 per cent as a mixture in almost equal parts of 8-oxyadenine and 2,8-dioxyadenine in the urine. Conversion of adenine to adenine nucleotide, probably by initial reaction with phosphoribosyl pyrophosphate and adenine-phosphoribosyltransferase, was at widely different rates in the organs with duodenum, kidney, liver, and lung high and heart, red blood cell, skeletal muscle and brain relatively low. Sites of formation of the two oxyadenines, probably by action of xanthine oxidase, were not determined.
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PMID:Metabolism by the rabbit of intravenously administered adenine. 87

Picroliv, the active principle of Picrorhiza kurrooa, and its main components which are a mixture of the iridoid glycosides, picroside-I and kutkoside, were studied in vitro as potential scavengers of oxygen free radicals. The superoxide (O2-) anions generated in a xanthine-xanthine oxidase system, as measured in terms of uric acid formed and the reduction of nitroblue tetrazolium were shown to be suppressed by picroliv, picroside-I and kutkoside. Picroliv as well as both glycosides inhibited the non-enzymic generation of O2- anions in a phenazine methosulphate NADH system. Malonaldehyde (MDA) generation in rat liver microsomes as stimulated by both the ascorbate-Fe2+ and NADPH-ADP-Fe2+ systems was shown to be inhibited by the Picroliv glycosides. Known antioxidants tocopherol (vitamin E) and butylated hydroxyanisole (BHA) were also compared with regard to their antioxidant actions in the above system. It was found that BHA afforded protection against ascorbate-Fe(2+)-induced MDA formation in microsomes but did not interfere with enzymic or non-enzymic O2- anion generation; and tocopherol inhibited lipid peroxidation in microsomes by both prooxidant systems and the generation of O2- anions in the non-enzymic system but did not interfere with xanthine oxidase activity. The present study shows that picroliv, picroside-I and kutkoside possess the properties of antioxidants which appear to be mediated through activity like that of superoxide dismutase, metal ion chelators and xanthine oxidase inhibitors.
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PMID:Picroliv, picroside-I and kutkoside from Picrorhiza kurrooa are scavengers of superoxide anions. 132 26

3-Morpholino-sydnonimine (SIN-1) is a NO-releasing compound which mimics the effects of cGMP through activation of soluble guanylyl cyclase. Its prodrug, molsidomine (SIN-10), does not release NO but does modulate various cell functions. These findings prompted us to study the effects of SIN-10 and SIN-1 on the respiratory burst in human neutrophils. SIN-10 was more effective than SIN-1 in inhibiting superoxide anion (O2-) formation induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe) and by C5a. The effects of SIN-1 and SIN-10 on O2- formation were additive or less than additive, indicating the sydnonimines acted through a common mechanism. The sydnonimines showed no effect on O2- formations induced by gamma-hexachlorocyclohexane, arachidonic acid and a phorbol ester. They did not inhibit O2- formation induced by xanthine oxidase, by autoxidation of pyrogallol and in a cell-free system from HL-60 leukemic cells. Neutrophils did not convert SIN-10 to SIN-1 as assessed by O2 consumption which accompanies NO release from SIN-1. The cell-permeant analogue of cGMP, N2,2'-O-dibutyryl guanosine 3':5'-monophosphate (Bt2cGMP), and SIN-10 but not SIN-1 inhibited fMet-Leu-Phe-induced O2 consumption. SIN-1 and SIN-10 slightly enhanced agonist binding to formyl peptide receptors, whereas Bt2cGMP was inhibitory. The sydnonimines did not affect GTP hydrolysis of heterotrimeric regulatory guanine nucleotide-binding proteins in HL-60 membranes. SIN-1 but not SIN-10 stimulated ADP-ribosylation of a 39-kDa protein in the cytosol of HL-60 cells. SIN-10 reduced fMet-Leu-Phe-induced rises in cytosolic Ca2+ concentration in neutrophils. These data suggest that SIN-10 inhibits the respiratory burst via a NO-independent mechanism which may involve inhibition of rises in cytosolic Ca2+ concentration.
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PMID:Molsidomine inhibits the chemoattractant-induced respiratory burst in human neutrophils via a no-independent mechanism. 132 80

We propose new hypotheses for the mechanisms of streptozotocin (STZ) and alloxan inducing experimental diabetes in animals. STZ is transported into pancreatic beta cells through glucose transporter in the cell membranes and attacks mitochondria. Mitochondrial ATP generation is inhibited and the resulting high concentration of intracellular ADP causes its degradation providing hypoxanthine, a substrate of xanthine oxidase (XOD) whose activity is intrinsically very high in beta cells. Then, XOD-catalyzing reaction is proceeded as proved by increased formation of uric acid and O2- radicals are produced, but beta cells are inefficient to scavenge these radicals because of their extremely low activity of superoxide dismutase. On the other hand, STZ directly activates XOD and enhances O2- generation. Consequently, pancreatic beta cells are dually suffered from O2- radicals or probably hydroxyl radicals derived from the former when exposed to STZ. Allopurinol, an inhibitor of XOD, can protect animals from the diabetogenic effect of STZ. In pancreatic beta cells, alloxan anion radicals are generated from alloxan probably mediated by the action of microsomal cytochrome P-450 system. These radicals have long half-life and directly damage DNA in vitro. The widely accepted hypothesis that the cause of alloxan-induced diabetes is attributable to O2- radicals formed from alloxan is excluded, because alloxan itself shows a very potent scavenging effect to O2- radicals. Therefore alloxan anion radicals seem to be directly related to the incidence of diabetes by alloxan.
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PMID:[New hypotheses for the mechanisms of streptozotocin and alloxan inducing diabetes mellitus]. 148 45

Reperfusion of ischaemic myocardium is necessary to sustain tissue viability (without it the tissue becomes necrotic), but reperfusion, on the other hand, can damage cells which have survived ischaemia. There is now considerable evidence that oxygen radicals, especially hydroxyl radicals produced via the Haber-Weiss and Fenton reactions, are responsible for reperfusion damage. Various investigators have reported that desferal, an iron chelator, has a beneficial effect on the myocardium during ischaemia and reperfusion. The aim of this study was two-fold: i) whether superoxide anions in the absence of LMWI can impair mitochondrial function, and ii) whether the protective effect of desferal on the mitochondrial function persists after withdrawal of desferal. Experiments were done on isolated rat hearts subjected to normothermic ischaemic cardiac arrest (NICA), with or without desferal, followed by 15-min reperfusion with desferal, followed by 15-min perfusion without desferal, or a hypoxanthine/xanthine oxidase medium that generates superoxide anions (with or without desferrioxamine (desferal) in the perfusate). Mitochondrial function (QO2 (state 3), ADP/O and OPR) as well as LMWI were measured. Our results indicated that i) superoxide anions and/or hydrogen peroxide can, independently of LMWI, damage the mitochondria, and ii) withdrawal of desferal after the respiratory burst resulted in the same or more severe mitochondrial damage than without any desferal.
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PMID:The protective effect of desferal on rat myocardial mitochondria is not prolonged after withdrawal of desferal. 156 53

Oxidative stress plays an important role in various types of cell injury and tumor promotion. Cells respond to oxidative stress in many ways including changes in membrane organization, ion movements, and altered gene expression, all of which contribute to the subsequent fate of affected cells. In this study, we investigated the expression of the proto-oncogenes c-fos, c-myc, and c-jun, which play a key role in proliferation and differentiation, using primary cultures of rat proximal tubular epithelium exposed to oxidative stress generated by the xanthine/xanthine oxidase system. This system generates superoxide and H2O2 in the extracellular space stimulating the release of active oxygen species from inflammatory cells. c-fos mRNA was expressed within 15 min, peaked at 30 min, and returned to constitutive levels by 3 h. c-jun mRNA began to rise after 30 min, peaked at 120 min, and remained above the constitutive levels up to 180 min. c-myc mRNA expression was less affected by the treatment, with levels increasing gradually over the 180 min period. The expression of c-fos was inhibited by superoxide dismutase but not by catalase and was super-induced by cycloheximide. H2O2 alone did not induce any c-fos mRNA in this system. Chelation of extracellular ionized calcium by EGTA or of intracellular ionized calcium by Quin 2/AM resulted in a marked decrease of c-fos expression. Two protein kinase C inhibitors, H-7 and staurosporine, partly diminished the expression of c-fos, whereas a third, 2-aminopurine, which has a broader spectrum of inhibiting protein kinases, almost completely abolished it. A poly ADP-ribosylation inhibitor, 3-aminobenzamide, had no effect on c-fos expression in this system. Our results show that oxidative stress provokes sequential expression of c-fos, c-jun, and c-myc, mRNA in this order. This c-fos expression appears to be largely controlled by calcium ion movement, which could include protein kinase C activation. Another protein kinase or kinases also appear to play an important role.
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PMID:Role of [Ca2+]i in induction of c-fos, c-jun, and c-myc mRNA in rat PTE after oxidative stress. 174 Feb 41

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

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

When isolated rat heart mitochondria are subject to xanthine/xanthine oxidase generated free radicals, nmol quantities of ADP are phosphorylated to ATP. This effect is proportional to xanthine oxidase concentration, and is relatively independent of ADP concentration. Exogenous superoxide dismutase partially suppresses the phosphorylation. Micromolar concentrations of iron salts completely eliminate the phosphorylation. Catalase has no effect. The likely electron source, then, is superoxide radicals. The reduced minus oxidised spectra of superoxide-bombarded mitochondria show that superoxide enters the electron transport chain by reducing cytochrome c and complex IV. Mitochondria retain their ability to phosphorylate ADP in more traditional ways under the experimental conditions described. Superoxide under physiological conditions in vivo may be a source of electrons for the oxidative phosphorylation of ADP.
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PMID:Superoxide radical as electron donor for oxidative phosphorylation of ADP. 216 11

We have studied the effect of H2O2 and O2- produced by xanthine and xanthine oxidase on NAD catabolism, poly(ADP-ribose) synthesis, and production of DNA single-strand breaks in C3H10T1/2 cells. The results show a correlation between the induction of DNA single-strand breaks, the decrease of NAD pool, and the accumulation of polymer. New techniques, based on affinity chromatography and reversed-phase high pressure liquid chromatography, have allowed an accurate determination of polymer contents and showed a 20-fold stimulation of polymer biosynthesis induced by active oxygen species. Inhibition experiments performed with 3-aminobenzamide have shown that the decrease in NAD levels after exposure of cells to active oxygen species was caused by stimulation of poly(ADP-ribosyl)ation and of another cellular process.
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PMID:Stimulation of poly(ADP-ribose) synthesis by free radicals in C3H10T1/2 cells: relationship with NAD metabolism and DNA breakage. 216 10


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