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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of NO and O2- free radicals generated from PMA (phorbol myristate acetate)-stimulated PMN (polymorphonuclear leukocytes) was studied by a nitroxide spin trap, DMPO (5,5-dimethyl-1-pyrroline-1-oxide). It was found that addition of L-arginine to the system would significantly decrease the trapped O2- by DMPO and addition of NG-monomethyl-arginine (NGMA) would significantly increase the trapped O2- by DMPO. It was proved that the formation of ONOO- by the reaction of NO and O2- was the main reason for the decrease of trapped O2- in the experiment with xanthine/xanthine oxidase and irradiation of riboflavin systems. The yield of NO during this process was calculated. The generation dynamic of NO was studied by a luminol-dependent chemiluminescence technique and it was found that after stimulation of PMN by PMA, there would be an immediate, significant chemiluminescence, which came mainly from the active oxygen free radicals generated by PMN. If L-arginine was added to this system, the chemiluminescence would increase about 100-fold, but NGMA inhibited the increase of the chemiluminescence. Ten minutes after addition of L-arginine, this increase did not change, the chemiluminescence peak decreased gradually, but the half life increased. The ESR and chemiluminescence properties of NO and ONOO- synthesized were also studied in model systems.
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PMID:Studies on nitric oxide free radicals generated from polymorphonuclear leukocytes (PMN) stimulated by phorbol myristate acetate (PMA). 868 50

Helicobacter pylori stimulated human neutrophils to produce oxygen radicals as evidenced by the production of chemiluminescence in the presence of luminol. The capacity of H. pylori to produce oxygen radicals from neutrophils was much higher than that of Escherichia coli and Staphylococcus aureus and is almost as strong as that of PMA. Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid) suppressed the chemiluminescence produced by H. pylori-stimulated neutrophils and also suppressed the chemiluminescence produced by a cell-free xanthine/xanthine oxidase reaction with luminol. Thus, it is indicated that this drug has the action of scavenging oxygen radicals. Gastric mucosal cells labelled with a fluorescent dye were damaged by the incubation of the cells with neutrophils and H. pylori, and this damage was protected by rebamipide. The protection of cell damage was ascertained as a decrease in the release of fluorescent dye into the incubation medium and a reduction in the distortion of cell geometry. The data suggest that H. pylori induce human neutrophils to produce oxygen radicals which are responsible for gastric mucosal cell damage and that rebamipide removes the oxygen radicals produced from H. pylori-activated neutrophils and thus reduces the gastric mucosal cell damage. These effects may account for the ulcerogenesis action of H. pylori and for part of the mechanism of the anti-ulcer action of rebamipide.
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PMID:Effects of rebamipide on gastric cell damage by Helicobacter pylori-stimulated human neutrophils. 886 35

Addition of PMA (phorbol myristate acetate)-stimulated neutrophils to an endothelial cell monolayer caused a significant increase in the intracellular peroxide level of the endothelial cells after 15 minutes and endothelial cell injury after 5 hours. Both the early and the late events were abolished in the presence of specific antibodies against CD (cluster of differentiation) 11a, CD11b, CD18 and ICAM (intercellular adhesion molecule) 1, but not CD11c. These antibodies affected neither the production of active oxygen species by the neutrophils nor the rate of adhesion of neutrophils to endothelial cells. Pretreatment of endothelial cells with allopurinol caused significant inhibition of both the early and the late events, suggesting that the binding of adhesion molecules may trigger the activation of XO (xanthine oxidase) of endothelial cells, and have the cells produce more hydrogen peroxide and ferrous ions, followed by producing more hydrogen peroxide. The hydrogen peroxide produced by endothelial cells themselves and by neutrophils may be converted to hydroxyl radicals by ferrous ions, which may cause lethal cell damage. Examination of XO activity in endothelial cells showed that the enzyme activity increased double within 15 minutes after the addition of PMA activated neutrophils. Monoclonal antibodies against CD11a and CD18 significantly inhibited the increased conversion of XD (xanthine dehydrogenase) to XO induced by PMA-activated neutrophils. Moreover, tyrosine kinase inhibitors also inhibited the increased conversion of XD to XO. These results indicate that the adhesion of activated neutrophils to endothelial cells via CD11a/CD18-ICAM-1 is involved in the conversion of XD to XO in endothelial cells, which results in endothelial cell injury.
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PMID:Cell adhesion molecule mediates endothelial cell injury caused by activated neutrophils. 889 63

The effect of four carotenoids (beta-carotene, lutein, bixin and canthaxanthin) on the respiratory burst of rat peritoneal macrophages was investigated. The results obtained showed that carotenoids suppressed the luminol-dependent chemiluminescence generated from PMA-stimulated macrophages at the beginning and after 2 min of the stimulation. Canthaxanthin and bixin had higher suppressive activity than beta-carotene and lutein. The changes in absorption spectra of carotenoids showed that the absorption by carotenoids was diminished during the stimulation of macrophages by PMA and their absorption peaks were either further diminished or blue-shifted after addition of L-arginine to the system, indicating that the carotenoids were consumed and converted to new compounds during the two processes. By using cell-free systems, it was found that carotenoids could scavenge superoxide anion generated by xanthine/xanthine oxidase system. Their ability to scavenge superoxide anion decreased in the order of canthaxanthin > bixin > lutein > beta-carotene. Canthaxanthin also showed the scavenging effect on superoxide anion generated from irradiation of riboflavin. The hydroxyl radical scavenging activity of carotenoids was investigated in the reaction system of Fe2+ and H2O2. There was little difference among their activities. The reaction between carotenoids and nitric oxide led to the decreasing absorption between 400 and 540 nm and the concomitant appearance of the new absorption peaks between 330 and 395 nm. Bleaching of beta-carotene, bixin and canthaxanthin by peroxynitrite resulted in the increasing absorption between 290 and 365 nm and the diminishing absorption between 400 and 500 nm. But the increasing absorption between 280 and 490 nm was observed in bleaching of lutein by peroxynitrite. Carotenoids inhibited thiobarbituric acid-reactive substance (TBARS) formation in AAPH-induced lipid peroxidation of PC liposomes in air. The results suggest that the suppressive effect of carotenoids on the respiratory burst of macrophages may be just a way by which carotenoids in vivo protect host cells and tissues from harmful effects of oxygen metabolites overproduced by macrophages and enhance the generation of specific immune responses.
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PMID:Effect of carotenoids on the respiratory burst of rat peritoneal macrophages. 965 74

We have studied the ability of propofol and Intralipid to inhibit reactive oxygen species generated either by stimulated human leucocytes or cell-free systems using luminol chemiluminescence. Human leucocytes were stimulated by a chemotactic peptide, FMLP 1 mumol litre-1, or by a phorbol ester, PMA (protein kinase C activator) 0.1 mumol litre-1. In cell-free experiments, superoxide-hydrogen peroxide, hypochlorous acid or hydroxyl radical-induced chemiluminescence responses were initiated by xanthine 0.1 mmol litre-1 with xanthine oxidase 10 mu. ml-1, NaOCl 70 mumol litre-1 and FeSO4 3 mumol litre-1, respectively. Propofol with Intralipid, and to a lesser degree Intralipid alone, produced a concentration-dependent reduction in chemiluminescence from stimulated leucocytes. Similar attenuations were also observed using propofol with Intralipid on xanthine with xanthine oxidase-, HOCl- and ferrous iron-induced chemiluminescence. However, Intralipid produced a reduction only at high concentrations. Intralipid produced marked decreases in ferrous iron-induced chemiluminescence. This study suggests that propofol had a direct scavenging activity against HOCl, superoxide-hydrogen peroxide and hydroxyl radical in the concentrations used. These direct scavenging effects may contribute to the effect of propofol on human leucocyte chemiluminescence.
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PMID:Propofol and intralipid interact with reactive oxygen species: a chemiluminescence study. 969 71

Reactive oxygen species (ROS) inhibit sperm movement and have been implicated in male infertility. In this study, we determined the effects of specific ROS produced by activated leukocytes on human spermatozoa and investigated their metabolic site of action. We used chemiluminescence and electron paramagnetic resonance (EPR) to characterize the ROS generated by both blood and seminal leukocytes. We also determined the effects of these ROS on sperm energy metabolism using biochemical analyses and flow cytometry. Both blood and seminal leukocytes produced the same characteristic ROS which were determined to be hydrogen peroxide (H2O2) and superoxide radicals (O2*-). EPR using the spin trapping technique indicated that superoxide radical-dependent hydroxyl radicals (HO.) were also generated. ROS generated by PMA-stimulated blood leukocytes (2-5 x 10(6)/ml) caused inhibition of sperm movement in 2 h (p < .01). Using the hypoxanthine/ xanthine oxidase (0.5 U/ml) system to generate ROS, we determined that spermatozoa ATP levels, after ROS treatment, were reduced approximately eight-fold in 30 min (0.10 x 10(10) moles/10(6) sperm cells) compared to control (0.84 X 10(-10) moles/10(6) sperm cells) (p < .01). Sperm ATP reduction paralleled the inhibition of sperm forward progression. Neither superoxide dismutase (100 U/ml) nor dimethyl sulfoxide (100 mM) reversed these effects; however, protection was observed with catalase (4 X 10(3) U/ml). Flow cytometric analyses of sperm treated with various doses of H2O2 (0.3 mM-20.0 mM) showed a dose-dependent decrease in sperm mitochondrial membrane potential (MMP); however, at low concentrations of H2O2, sperm MMP was not significantly inhibited. Also, sperm MMP uncoupling with CCClP had no effect on either sperm ATP levels or forward progression. These results indicate that H2O2 is the toxic ROS produced by activated leukocytes causing the inhibition of both sperm movement and ATP production. O2*- and HO. do not play a significant role in these processes. Low concentrations of H2O2 causing complete inhibition of sperm movement and ATP levels inhibit sperm energy metabolism at a site independent of mitochondrial oxidative phosphorylation.
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PMID:Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism. 1023 30

The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isolated from the aerial flowering parts of Helichrysum picardii Boiss. & Reuter (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in stimulated rat peritoneal leukocytes, and for its effects on leukocyte granular enzyme release, cell viability and interactions with reactive oxygen species. Gnaphalin dose-dependently inhibited generation of the cyclo-oxygenase metabolite thromboxane B2 (IC50 = 39.9 +/- 3.9 microM), and of the 5-lipoxygenase metabolite leukotriene B4, although the potency was two-fold less (IC50 = 81.8 +/- 12.9 microM). At concentrations of 6 to 320 microM, gnaphalin did not affect secretion of the pro-inflammatory enzymes lysozyme, myeloperoxidase and beta-glucuronidase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged superoxide radicals generated in the hypoxanthine/xanthine oxidase system (IC50 = 40 microM) and by PMA-stimulated leukocytes (> 60% at 500 microM), directly inhibited xanthine oxidase (85% at 395 microM) and inhibited Fe(3+)-ascorbate-induced liposomal peroxidation (IC50 = 215 microM). Thus, like some other flavonoids found in medicinal herbs, gnaphalin possesses an array of potentially beneficial anti-eicosanoid and free-radical scavenging properties which may alongside other constituents contribute to the claimed medicinal properties of the plant from which it is derived.
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PMID:Inhibition of leukocyte eicosanoid generation and radical scavenging activity by gnaphalin, a lipophilic flavonol isolated from Helichrysum picardii. 1048 68

HL-60 cells differentiated with DMSO increased their rates of uptake of ascorbate when they were activated with PMA. The rates observed after this activation were essentially the same as those with dehydroascorbic acid as the original transport substrate. The effect of activation was sensitive to the antioxidant enzymes superoxide dismutase and catalase. When ascorbate was oxidized in situ by chemical or enzymic oxidation, the rates of uptake were similar to those after activation of the cells by phorbol ester; however, in the latter case the extracellular vitamin remained largely in the reduced form and there was very little loss by degradation, whereas after immediate oxidation no more reduced ascorbate could be found outside the cells after a few minutes and a significant part of the total vitamin was lost. The generation of superoxide by xanthine/xanthine oxidase stimulated the uptake of ascorbate much less than the activation by phorbol ester; H(2)O(2) was even less effective. Stimulation of the uptake by phorbol ester was also insensitive to GSH, in contrast with stimulation by the chemical oxidation of ascorbate. Stimulation of ascorbate uptake by phorbol ester was sensitive to the respiratory-burst inhibitor diphenyliodonium as well as the protein kinase C inhibitor staurosporine, indicating the respiratory burst as the cause of stimulation. Activation of the cells by the phorbol ester also stimulated the uptake of dehydroascorbate as the original substrate, in a manner insensitive to antioxidants or inhibitors of the respiratory burst. In all cases the intracellular vitamin was completely in the reduced form. Kinetic characterization by the calculation of maximal velocities and apparent K(m) values and assaying for the dependence of uptake rates on the ionic milieu and for inhibition by glucose analogues and inhibitors of glucose transport revealed that after treatment with phorbol ester the uptake of total vitamin C in differentiated HL-60 cells was largely due to the low-affinity high-capacity glucose transporter. In contrast, in non-stimulated cells reduced ascorbate was taken up by the Na(+)-dependent high-affinity low-capacity ascorbate transporter. This change was probably due to the oxidation of ascorbate and, simultaneously, the recruitment of additional transporter molecules to the cell surface.
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PMID:Interaction of respiratory burst and uptake of dehydroascorbic acid in differentiated HL-60 cells. 1062 Apr 94

The scavenging effects of total flavonoids of Lycium barbarum L. (TFL) were studied by using ESR-spin trapping technique and the inhibitory effects on heat output of both polymorphonuclear leukocyte(PMN) respiration burst and L1210 cells were measured by using microcalorimetric technique. TFL (0-217 mg/L) could scavenge O2-. in xanthine/xanthine oxidase (Xan/XO)system, with scavenging rate of 0-51%. TFL(7.5-200 mg/L)could scavenge OH. produced in Fenton reaction and the scavenging rate is between 20% to 72%. Those effects were concentration-dependent. Furthermore, TFL(0.56 g/L)could completely inhibit the heat output from PMA-stimulated PMN and TFL(1.0-5.0 g/L)could inhibit the heat output from L1210 cells.
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PMID:[Scavenging effect of total flavonoids of lycium barbarum L on active oxygen radicals and inhibitory effects on heat output from L1210 cells]. 1068 19

Activation of the respiratory burst of granulocytes and macrophages by invading microorganisms is a key first line cellular defence against infection. Failure to generate this response leads to persistent life-threatening infection unless appropriate antibiotic treatment is given. The respiratory burst of neutrophils is usually measured spectrophotometrically by following ferricytochrome c reduction, and histologically by using the tetrazolium salt, nitroblue tetrazolium, which is reduced intracellularly to an insoluble formazan. In both assays, reduction is mediated by superoxide generated via NADPH oxidase. Because ferricytochrome c has a high molecular mass and high background absorbance at 550 nm, the assay lacks sensitivity and is not ideally suited to microplate measurement. We have circumvented these limitations by using the cell-impermeable, sulfonated tetrazolium salt, WST-1, which exhibits very low background absorbance and is efficiently reduced by superoxide to a stable water-soluble formazan with high molar absorptivity. This has permitted adaptation of the WST-1 assay to microplate format while retaining sensitivity. Reduction of WST-1 by activated human peripheral blood neutrophils correlated closely with ferricytochrome c reduction across a range of PMA concentrations and with time of activation by PMA and fMLP. Reduction of WST-1 was inhibited by 98% by superoxide dismutase (20 microg/ml) and by 88% by the NADPH oxidase inhibitor, diphenyleneiodinium (10 microM) but was resistant to catalase, azide and the NADH oxidase inhibitor, resiniferatoxin. WST-1 and ferricytochrome c reduction were also compared using xanthine/xanthine oxidase to generate superoxide. Under optimised assay conditions, both WST-1 and ferricytochrome c reduction were directly proportional to added xanthine. WST-1 generated approximately 2-fold greater increase in absorbance than ferricytochrome c at their respective wavelengths, and this translated into increased assay sensitivity. Addition of the intermediate electron acceptor, 1-methoxy phenazine methosulfate, increased the background of the neutrophil assay but did not affect the overall magnitude of the response. We have used the WST-1 assay to assess human neutrophil dysfunction and to compare anti-inflammatory activity.
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PMID:Superoxide produced by activated neutrophils efficiently reduces the tetrazolium salt, WST-1 to produce a soluble formazan: a simple colorimetric assay for measuring respiratory burst activation and for screening anti-inflammatory agents. 1075 36


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