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)

Isolated rat pancreatic beta cells in monolayer culture were shown to be protected from the cytotoxic effect of streptozotocin (STZ) by allopurinol. Pretreatment with allopurinol for 2 h caused dose-dependent inhibition of the decreased secretion of insulin by the cells induced by STZ (2 mM, for 1 h), 500 microM allopurinol causing complete inhibition of this effect of STZ. Pretreatment with allopurinol (250 microM) also prevented the rapid decrease in intracellular adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide concentrations in beta cells induced by treatment with STZ. High performance liquid chromatography revealed that the intracellular concentration of uric acid in STZ-treated cells was about 3 fold that of control cells. This finding suggests that the reaction of xanthine oxidase is facilitated in the cells exposed to STZ probably due to an increased supply of substrate resulting from decrease in intracellular ATP. Based on these results, a possible mechanism of the effect of allopurinol on the cytotoxic effect of STZ via xanthine oxidase is discussed.
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PMID:Allopurinol protects pancreatic beta cells from the cytotoxic effect of streptozotocin: in vitro study. 214 33

The hydroxyl radicals (HO.) spin adduct of 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) was obtained in the hypoxanthine-xanthine oxidase (HX-X.O.) system in the presence of isolated islet cells by using electron spin resonance spectroscopy. There was a significant increase in the concentration of DMPO-OH spin adduct dependent on the increase in a number of islet cells. In the absence of islet cell, the DMPO-OOH spin adduct formed by superoxide together with a small amount of DMPO-OH spin adduct was detected in HX-X.O. system. These results suggest that HO. is greatly produced in the HX-X.O. system in the presence of islet cells. The generation of HO. was partially inhibited by the addition of superoxide dismutase or catalase and completely by the combined use of both enzymes. Iron-chelator, diethylenetriaminepentaacetic acid and iron-binding protein, apotransferrin also inhibited the generation of HO., suggesting a possible participation of a trace iron in the islet cells. The inhibition of insulin release from islet cell, as well as the amount of DMPO-OH spin adduct, was dependent on the concentration of X.O. These results indicate that the HO. is produced by the site-specific action with islet cells in HX-X.O. system, suggesting a possible involvement of HO. in the oxygen damages of islet cells.
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PMID:[Studies on biological damage by active oxygens. III. Generation of hydroxyl radical and inhibition of insulin release in hypoxanthine-xanthine oxidase system in the presence of pancreatic islet cells]. 266 18

Xanthine/xanthine oxidase and H2O2 stimulated sugar transport. Application of superoxide dismutase and catalase to the cells showed an inhibitory effect on these agent-stimulated sugar transports. Addition of amiloride and 4-acetamide-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), which abolish the cytoplasmic alkalinization, inhibited the stimulation of sugar transport by xanthine/xanthine oxidase in the presence of catalase. The calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and trifluoperazine inhibited H2O2-stimulated sugar transport. These results suggest that O2- stimulates sugar transport in an intracellular pH-dependent manner and that H2O2 stimulates sugar transport in a calcium-calmodulin-dependent manner. These mechanisms may be involved in sugar-transport stimulation in mouse fibroblast BALB/3T3 cells by the tumor-promoting phorbol ester phorbol-12,13-dibutyrate and insulin, since the stimulatory effects of these agents were inhibited by scavengers of oxygen radicals.
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PMID:Mechanism of O2- (-) and H2O2-induced stimulation of sugar transport in mouse fibroblast BALB/3T3 cells. 284 89

In this study we prepared sarcolemmal fractions from bovine and rat hearts; their Na+K+ ATPase activities, measured in the presence of saponin to unmask latent Na+K+ ATPase, were 59.4 and 48.8 mu mol Pi/mg protein.h, respectively. The rate of Na+ dependent Ca2+ uptake was linear for the first 10 s and a plateau was reached in 3 min. Oxidation by free radical generation either with H2O2, FeSO4 plus DTT or xanthine oxidase plus hypoxanthine stimulated Na+/Ca2+ exchange in a time-dependent manner. The stimulation was abolished by deferoxamine or o-phenanthroline. By contrast, oxidation by HOCl inhibited Na+/Ca2+ exchange in proportion to its concentration, and this inhibition was antagonized by DTT. DTT alone had no effect on the exchange. Insulin stimulated Na+/Ca2+ exchange, its maximal effect was attained after 30 min incubation with 100 mu units/ml. N-ethylmaleimide inhibited the exchange both in the presence and in the absence of insulin. Sarcolemmal fractions prepared from hearts of alloxan-treated, acutely diabetic rats showed a significant decrease in Na+/Ca2+ exchange. Addition of insulin in vitro significantly stimulated Na+/Ca2+ exchange of both diabetic and control groups. The results indicate that sarcolemmal Na+/Ca2+ exchange function is modulated by oxidation-reduction states and by the presence of insulin.
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PMID:Na+/Ca2+ exchange of isolated sarcolemmal membrane: effects of insulin, oxidants and insulin deficiency. 285 14

In the isolated rat liver perfused in situ stimulation of the nerve bundles around the portal vein and the hepatic artery caused an increase of urate formation that was inhibited by the alpha 1-blocker prazosine and the xanthine oxidase inhibitor allopurinol. Moreover, nerve stimulation increased glucose and lactate output and decreased perfusion flow. Infusion of noradrenaline had similar effects. Compared to nerve stimulation infusion of glucagon led to a less pronounced increase of urate formation and a twice as large increase in glucose output but a decrease in lactate release without affecting the flow rate. Insulin had no effect on any of the parameters studied.
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PMID:Increase of urate formation by stimulation of sympathetic hepatic nerves, circulating noradrenaline and glucagon in the perfused rat liver. 329 88

Glucose, insulin, potassium (GIK: 300 g glucose + 50 U insulin + 80 mEq KC1/L) was administered to anesthetized dogs as a 30-ml bolus followed by 1.5 ml/kg/h for 2 h. Five populations were studied: control (C, n = 6); 60 min hypothermic arrest both without (I, n = 6) and with pretreatment (I + GIK, n = 6); 60 min hypothermic arrest followed by reperfusion without (R, n = 6) and with pretreatment (R + GIK, n = 6). Glycogen content declined during the ischemic and reperfusion periods whether or not GIK pretreatment was utilized. Glycogen values did not differ significantly among the four groups. GIK pretreatment significantly protected sarcoplasmic reticulum (SR) calcium uptake rates. SR Ca2+ + Mg2+ adenosine triphosphatase (ATPase) activity was unaffected in the I group, depressed in the R group, but protected by GIK pretreatment. Myofibrillar pCa-ATPase activity was significantly depressed in the I group and unaffected by GIK pretreatment. In the R + GIK group, myofibrillar pCa-ATPase activity was identical to controls at all calcium concentrations except for Vmax. In vitro, generation of the superoxide anion by a xanthine-xanthine oxidase system at pH 7.0 significantly depressed both SR calcium uptake and ATPase activity, and this depression was partially reversible by glucose. Generation of the hydroxyl free radical and pH 6.4 significantly depressed calcium uptake but not ATPase activity, and this depression was reversible with glucose + superoxide dismutase. GIK pretreatment exerts a protective effect on the excitation-contraction coupling system during hypothermic global ischemia and reperfusion. Glycogen augmentation after short-term GIK infusion was not significantly different. It is hypothesized that an additional mechanism by which GIK may protect subcellular function is by serving as a scavenger of free radicals generated during the ischemic/reperfusion process.
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PMID:Glucose, insulin, potassium protection during the course of hypothermic global ischemia and reperfusion: a new proposed mechanism by the scavenging of free radicals. 618 57

3T3 L1-cells, which undergo adipose conversion in vitro, possess a stimulus-sensitive H2O2-generating system in their plasma membrane, and its properties are virtually identical with those of the insulin-sensitive human fat-cell oxidase [Krieger-Brauer and Kather (1992) J. Clin. Invest. 89, 1006-1013]. Insulin and insulin-like growth factor I were found to be active stimulators of NADPH-dependent H2O2 generation. Surprisingly, the acidic (a) and basic (b) isoforms of fibroblast growth factor (FGF) as well as the AA and BB homodimers of platelet-derived growth factor (PDGF) had antagonistic effects on NADPH-dependent H2O2 generation in plasma membranes which were parallelled by corresponding changes in H2O2 accumulation in intact cells. bFGF and PDGF BB (which inhibit NADPH-dependent H2O2 generation) prevented the adipose conversion of 3T3 L1-preadipocytes, and this effect could be reversed by exogenously supplied H2O2. Conversely, aFGF and PDGF AA, which stimulated H2O2 generation, accelerated adipocyte conversion in the presence of insulin and were adipogenic in themselves. Consistently, expression of the adipocyte phenotype induced by insulin, dexamethasone and isobutylmethylxanthine was enhanced in the presence of exogenous hypoxanthine/xanthine oxidase, whereas antioxidants, such as N-acetylcysteine or ascorbate, suppressed the process of differentiation. It is concluded that the H2O2 produced in response to hormones and cytokines may contribute to the development and maintenance of the differentiated state.
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PMID:Antagonistic effects of different members of the fibroblast and platelet-derived growth factor families on adipose conversion and NADPH-dependent H2O2 generation in 3T3 L1-cells. 773 96

Troglitazone (CS-045), a newly developed antidiabetic thiazolidinedione that enhances insulin sensitivity, is similar in structure to several antioxidants, including alpha-tocopherol and probucol. The in vitro antioxidant activity of troglitazone has been demonstrated in alloxan-induced hyperlipoperoxidemic and hyperlipidemic mice. In this study, we found that troglitazone had a scavenging effect on reactive oxygen produced by xanthine-xanthine oxidase and generated by stimulated neutrophils and tends to be the radical form. Our results suggest that troglitazone is an antioxidant similar to alpha-tocopherol. However, under the same conditions, pioglitazone, another thiazolidinedione drug, did not have a scavenging effect. The antioxidant action of troglitazone, which is attributable to the similarity of its molecular structure to that of alpha-tocopherol, may be of benefit in preventing diabetic vascular complications, in addition to having hypoglycemic and hypolipidemic effects.
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PMID:Troglitazone has a scavenging effect on reactive oxygen species. 919 46

The role of reactive oxygen species in diabetes and its complications are well known. Two therapeutic agents commonly used in the treatment of diabetes are the sulfonylureas, gliclazide and glibenclamide. These drugs effectively reduce blood sugar in non-insulin dependent diabetes millitus by augmenting insulin release. Gliclazide is known to be a general free radical scavenger as demonstrated by inhibition of o-dianisidine photo-oxidation. In this study, the effects of gliclazide and glibenclamide on free radicals were examined in vitro, using electron spin resonance (ESR) spectroscopy. Superoxide radical (O2.-) generated from hypoxanthine-xanthine oxidase system, or hydroxyl radical (.OH) generated by the Fenton reaction, were analyzed as spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). NO was generated from 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7), and analyzed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (carboxy-PTI) produced from the reaction between 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and NO. Gliclazide scavenged O2.-, .OH and NO in a dose-dependent manner whereas glibenclamide was without effect. These findings suggest that gliclazide is not only effective in reducing blood sugar but also may be beneficial by inhibition of lipid and protein denaturation, which leads to the development of diabetic complications.
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PMID:Gliclazide scavenges hydroxyl, superoxide and nitric oxide radicals: an ESR study. 922 46

Insulin-induced increases in blood flow are hypothesized to enhance overall glucose uptake by skeletal muscle. Whether the insulin-mediated changes in blood flow are associated with altered blood flow distribution and increased capillary recruitment in skeletal muscle is not known. In the present study, the effects of insulin on hemodynamic parameters in rat skeletal muscle in vivo were investigated. Mean arterial blood pressure, heart rate, femoral blood flow, hind leg vascular resistance, and glucose uptake were measured in control and euglycemic insulin-clamped (10 mU x min(-1) x kg[-1]) anesthetized rats. Blood flow distribution within the hind leg muscles was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for capillary xanthine oxidase. Insulin treatment had no effect on heart rate but significantly increased arterial blood pressure (12 mmHg) and femoral blood flow (80%) and decreased hind leg vascular resistance (31%). Changes were similar in magnitude and in time of onset to those reported in humans. Insulin treatment increased hind leg glucose uptake approximately fourfold and also increased hind leg 1-MX metabolism by 50%, suggesting increased exposure to endothelial xanthine oxidase. To ascertain whether the increased 1-MX metabolism was simply due to increased bulk femoral blood flow, epinephrine was infused at a dose (0.125 microg x min(-) x kg[-1]) chosen to match the insulin-induced increase in femoral blood flow. This dose of epinephrine had no significant effects on arterial blood pressure or heart rate but increased femoral blood flow and lowered hind leg vascular resistance to a similar extent as insulin. Epinephrine did not significantly alter 1-MX metabolism as compared with control animals. These results demonstrate that insulin increases total hind leg blood flow and metabolism of 1-MX, suggesting a recruitment of capillary blood flow in rat hind leg not mimicked by epinephrine.
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PMID:Hemodynamic actions of insulin in rat skeletal muscle: evidence for capillary recruitment. 928 35


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