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)

It has been proposed that oxygen free radical production is an important mediator of the myocardial dysfunction during the course of acute ischemia. We tested this hypothesis by characterizing the pathway of calcium efflux across sarcoplasmic reticulum (SR) membranes affected by oxygen free radicals. The effect of oxygen free radicals on the steady state calcium load, calcium permeability, and Ca,Mg-ATPase activity of isolated canine cardiac SR vesicles was investigated at pH 7.0. In vitro generation of oxygen free radicals by xanthine oxidase (0.09 units/ml), acting on xanthine in doses up to 50 microM as a substrate, increased the permeability of the SR vesicles to calcium, determined by measuring net efflux of calcium after stopping pump-mediated fluxes, and decreased total intravesicular calcium and free intravesicular calcium with no effect on Ca,Mg-ATPase activity. The effect of oxygen free radicals on calcium permeability was calcium gradient-dependent. Xanthine alone or xanthine plus denatured xanthine oxidase had no effect on this system. Superoxide dismutase (SOD, 56 units/ml), but not denatured SOD, significantly inhibited the effect of xanthine-xanthine oxidase reaction. The calcium permeability of the SR membrane decreased with decreasing calcium load. In addition, inasmuch as extravesicular calcium exerts only a slight effect on calcium permeability, the decrease in the permeability with calcium load is specifically related to the calcium load. Oxygen free radical-induced increase in calcium permeability was unaffected by Mg concentration between 2.1 and 21 mM. In summary, our data reveal that .O2- can produce a diminished level of accumulated calcium, which is reflected by the decreased calcium load and an increase in passive calcium permeability, and that the decreased calcium accumulation in the presence of the xanthine-xanthine oxidase system may not be mainly due to an inhibited calcium pump but due to an increased calcium permeability. Our results also suggest that increased SR membrane passive calcium permeability induced by oxygen free radicals is not carrier mediated. It is postulated that, with the oxygen free radical-mediated progressive increase in calcium permeability, free cytosolic calcium concentrations would increase in ischemic myocardium.
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PMID:The effect of oxygen free radicals on calcium permeability and calcium loading at steady state in cardiac sarcoplasmic reticulum. 284 52

The relation between ESR-detectable Cu(II) and Cu,Zn-superoxide dismutase activity was examined. The Cu(II) spin numbers per one unit of SOD were 6.26 X 10(12) (+/- 0.51 X 10(12] spins in several preparations of recombinant human Cu,Zn-SOD, native placental, and erythrocyte SOD. Measurement could be performed over a wide range of pH (4.0-10.0), preferably at temperatures below -40 degrees C. The data obtained by this method correlated well to the results obtained by the method of Fridovich et al. using the xanthine-xanthine oxidase system (correlation coefficient 0.995). The specific activity of SOD was proportional to the Cu(II) content measured by ESR, but not to the total Cu content measured by atomic absorption. This indicates that it is important to measure the Cu(II) content for determining Cu,Zn-SOD activity.
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PMID:Relation between ESR-detectable Cu(II) and superoxide dismutase activity. 285 62

A procedure to induce hemolysis by the hypoxanthine-xanthine oxidase reaction was developed and applied to vitamin E deficient red blood cells (RBCs) in rats. The reaction system was as follows: 0.16 mM hypoxanthine, 0.05 U/ml xanthine oxidase in 2.5% RBC suspensions with an isotonic buffer (pH 7.4) containing 10 mM phosphate buffer and 125 mM saline (277 mOsm). Hemolysis was observed to depend on the vitamin E concentrations in the RBCs. Hemolysis was inhibited by catalase but not by SOD. After the reaction with vitamin E deficient RBCs, an increase in TBARS in the aqueous phase of the reaction mixture was observed. This accompanied the increase in fluorescent substances in the lipid extracts, in association with a significant decrease in the PE and PS of the RBCs, and a decrease in arachidonic acid in membrane lipids. The above changes were almost completely inhibited by tocopherol incorporated into vitamin E deficient RBCs.
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PMID:Hemolysis and membrane lipid changes induced by xanthine oxidase in vitamin E deficient red cells. 302 41

Even when cytoplasmic scavenging activities are plentiful, yeast cells (S. cerevisiae) remain particularly sensitive towards reactive oxygen species generated in the extracellular space (either by the xanthine/xanthine oxidase reaction or by the redox cycling of menadione). A sharp reduction of the extent of cellular alterations when SOD and/or catalase were supplemented in the incubation buffer, points to a contribution of both O-.2 and H2O2 in the toxic process. Although oxygen metabolites as well as t-butylhydroperoxide (tBH), a highly toxic organic peroxide, may be directly responsible for cellular damage, their toxicity is largely reduced in the presence of Desferal. A role of metal ions in potentiating the toxicity points to the involvement of OH. radicals, actually produced in the medium. With tBH, metal cations would be rather active in promoting peroxidative chain reactions. In the case of an extracellular oxidative attack, it may be foreseen that the plasma membrane will form a preferential target. An increased permeability of the plasma membrane towards ionized molecules and uncharged polycarboxylic acids is indeed observed after an oxidative treatment. The loss of selective permeability is, as a rule, correlated with a drop in viability. Early alterations, disrupting the functional organization of the plasma membrane have been sought. The permease involved in the active transport of purine(s) has appeared to be an appropriate marker for checking its functional integrity. This transport function appears to be very sensitive to damage induced by O-.2 generators, particularly under conditions in which the resulting lethality is still kept low and in which the energization of active transport processes remains unimpaired.
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PMID:Sensitivity of yeast cells to reactive oxygen species generated in the extracellular space. 302 7

When dehydration, infection, and mechanical trauma are prevented, procedures (such as cooling and/or oral antithromboxane) designed to diminish ischemia in experimental zone-of-stasis burns have been associated with no or only minor improvement in wound healing. To test the hypothesis that ongoing skin damage occurring postburn (PB) may in part be due to release of oxygen-derived free radicals during the 16-hour through 4-day PB period of reperfusion in such burns, beginning immediately and for a period of 5 days PB, equal numbers of guinea pigs received: allopurinol 150 mg/kg PO q 6 h vs. placebo, dimethylsulfoxide (DMSO) 75% applied topically q 12 h vs. placebo, or yeast-derived superoxide dismutase coupled with polyethylene glycol (PEG-SOD, Pharmacia) 10,000 U (Fridovich) given IV q 8 h producing a concentration of 16 U/cc of plasma 8 hr after injection vs. placebo. Gross and histologic examination of wounds by a 'blinded' investigator at 1 week and 3 weeks PB revealed no difference between treatment and control groups when rates of re-epithelialization and frequencies of hair-follicle retention were compared. Using the dosages, routes, and model described, treatment of a zone-of-stasis burn with PO allopurinol (a xanthine oxidase inhibitor), topical DMSO (a scavenger of the hydroxyl radical), or IV PEG-SOD (a scavenger of the superoxide radical) during the first 5 days PB was associated with no increase in the rate of re-epithelialization or frequency of hair follicle retention at 1 and 3 weeks PB when compared with controls.
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PMID:Oxygen-derived free radical inhibition in the healing of experimental zone-of-stasis burns. 302 94

Free radicals acting at sensitive subcellular sites, appear to play a pivotal role in both the deleterious and beneficial effects of maturation and senescence of various plant organs--leaves, flowers, and fruit. As evidenced by ESR spectrometry, spin trapping, specific membrane phase transition studies and enzyme kinetics, an important factor in the above processes appears to be lipoxygenase activity producing polyunsaturated fatty acid (PUFA) hydroperoxides and subsequently several free radical species and senescence-promoting compounds such as ethylene, malondialdehyde and jasmonic acid. The most intensely investigated are the oxy-free radical species including O2-., .OH, RO., ROO., PUFA and semiquinone free radicals. Higher plants are equipped with ways and means to combat free radicals and these may be classified under two general headings; (a) direct scavengers including SOD, ascorbic acid, and alpha-tocopherol acting in concert (b) incipient preventative mechanisms against radical formation, these include xanthine oxidase inhibitors, strategies based on endogenous H2O2 disposal in the form of peroxidative enzymes and glutathione turnover, and Ca2+ channel blockers. The antisenescence phytohormone cytokinin appears to possess a dual effect and may act in both capacities. The special case of delayed free radical formation in comparatively dry biological systems such as seeds is detailed, and specific free radical-generating photosensitizer compounds are also discussed.
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PMID:Plant senescence processes and free radicals. 307 46

Xanthine oxidase with acetaldehyde as substrate (the XOA system) generated superoxide anion and hydrogen peroxide, but this system had only weak bactericidal activity. Addition of Fe2+ and EDTA to the XOA system (XOA-Fe-EDTA system) increased bactericidal activity against Staphylococcus aureus, Escherichia coli, Listeria monocytogenes and Salmonella typhimurium, although both Mycobacterium tuberculosis and Candida albicans remained highly resistant. Catalase (H2O2 scavenger) and mannitol (.OH scavenger) almost completely inhibited the bactericidal activity of the XOA-Fe-EDTA system whereas SOD (O2- scavenger) was less inhibitory. Azide (1O2 scavenger) caused no such inhibition. The results suggest the possible role of .OH, H2O2 and O2- in the XOA-Fe-EDTA-mediated antimicrobial system, as effector molecules. There was no correlation between resistance of a given bacterium to active oxygen and the level of endogenous active oxygen-scavengers.
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PMID:Susceptibility of micro-organisms to active oxygen species: sensitivity to the xanthine-oxidase-mediated antimicrobial system. 312 35

This assay for superoxide dismutase (SOD, EC 1.15.1.1) activity involves inhibition of nitroblue tetrazolium reduction, with xanthine-xanthine oxidase used as a superoxide generator. By using a reaction terminator, we can determine 40 samples within 55 min. One unit of activity of pure bovine liver Cu,ZnSOD and chicken liver MnSOD was expressed by 30 ng and 500 ng of protein, respectively. The mean concentrations of Cu,ZnSOD as measured by this method in blood from normal adults were 242 (SEM 4) mg/L in erythrocytes, 548 (SEM 20) micrograms/L in serum, and 173 (SEM 11) micrograms/L in plasma. The Cu,ZnSOD concentrations in serum and plasma of patients with cancer of the large intestine tended to be less and greater than these values, respectively, but not statistically significantly so.
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PMID:A simple method for clinical assay of superoxide dismutase. 334 99

This study describes the effect of oxygen radicals on the ultrastructure of the isolated Langendorff-perfused rat heart. Oxygen radicals were enzymatically generated by xanthine oxidase (0.025 U/ml) and hypoxanthine (0.96 mM). Hearts were perfusion-fixed for electron microscopy and stereological technique was performed to obtain estimates of volume fractions (Vv) of different tissue components. Perfusion with oxygen radicals resulted in areas with severely damaged myocardial cells. These changes included swelling and cristolysis of mitochondria, disruption of filaments, development of intracellular edema and focal disruption of the sarcolemma. Stereological examination revealed few alterations after 5 min perfusion with oxygen radicals. After 10 min perfusion with oxygen radicals, however, the Vv (myocyte/myocardium) increased from 0.542 +/- 0.042 (mean +/- S.D.) to 0.663 +/- 0.144, and this paralleled the development of Vv (cellular edema/myocyte) being 0.047 +/- 0.028. Vv (capillary wall/capillary) increased from 0.215 +/- 0.046 to 0.411 +/- 0.123 indicating endothelial swelling. Although the mitochondria appeared swollen, Vv (mitochondria/myocyte) remained constant. The effect of a 35 min recovery period on the ultrastructure was minor. The application of SOD and catalase together with xanthine oxidase and hypoxanthine reduced the observed changes significantly, thus proving the participation of oxygen radicals. This study confirms that oxygen radicals can induce major alterations in myocardial ultrastructure.
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PMID:Ultrastructural changes induced in the isolated rat heart by enzymatically generated oxygen radicals. 361 20

Changes in deformability of rabbit and human erythrocytes caused by exposure in vitro to the oxygen free radical generator hypoxanthine and xanthine oxidase were studied. The deformability reduction observed after 30 min of exposure to hypoxanthine-xanthine oxidase could be prevented by pretreatment with SOD, while after only 5 min of such exposure allopurinol and catalase also appeared to have a protective effect. Exposure of human erythrocytes to hypoxanthine and xanthine oxidase in Krebs solution prevented an otherwise occurring hemolysis. Exposure to both substances or to xanthine oxidase alone in Dulbeccos phosphate solution produced a reduction in deformability. The results indicate that exposure of erythrocytes to free oxygen radicals reduces deformability and that this effect may contribute to the myocardial dysfunction and the epicardial erythrostasis observed during open-heart surgery.
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PMID:Effect of oxygen free radicals on rabbit and human erythrocytes. Studies on cellular deformability. 381 94


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