Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of quinones (benzoquinone, menadione, and doxorubicin) on the superoxide production in cell free systems (xanthine oxidase and rat liver microsomes) and of polycationic electrolyte- and latex-stimulated rat peritoneal macrophages have been studied. Contradictory results were obtained in cell free systems when two traditional assays for detection of superoxide ion, the cytochrome c reduction and the lucigenin-dependent chemiluminescence (CL), were used: all quinones inhibited the lucigenin-dependent CL at sufficiently large concentrations, but they did not inhibit at all the reduction of cytochrome c. It was proposed that the cytochrome c assay gave erroneous results due to the reversibility of the interaction of semiquinones with dioxygen. The effect of quinones on the superoxide production by peritoneal macrophages was biphasic: all quinones stimulated the O2-. formation at low concentrations and inhibited it at elevated concentrations. It was concluded that among the quinones studied, only menadione was capable of stimulating the superoxide production via a one-electron transfer mechanism in cell free systems, while the stimulatory effect of small concentrations of quinones on the O2-. production in macrophages was possibly due to their action on the activation of NADPH oxidase.
 ...
PMID:Are quinones producers or scavengers of superoxide ion in cells? 216 57

Oxygen-derived free radicals have been implicated as a mediator of the microvascular and parenchymal cell injury associated with reperfusion of ischemic tissues. Xanthine oxidase and neutrophilic NADPH oxidase are commonly invoked to explain reperfusion-induced production of oxygen radicals. The strengths and weaknesses of evidence used to suggest the involvement of both sources are discussed. Evidence is also presented which suggests that xanthine oxidase and neutrophils are redundant yet interactive mechanisms that play an important role in reperfusion injury.
 ...
PMID:Mechanisms of cellular injury: potential sources of oxygen free radicals in ischemia/reperfusion. 270 Mar 73

Reactive oxygen metabolites (ROMs) are partially reduced oxygen species that include superoxide, hydrogen peroxide, hydroxyl radical, and hypohalous acids. Formation of superoxide or hydrogen peroxide may be injurious to tissue directly; however, it is thought that the primary mediators of tissue damage are the secondarily derived oxidants such as hydroxyl radical and hypohalous acid. The gastrointestinal tract is particularly well endowed with the enzymatic machinery necessary to form large amounts of ROMs. Sources of ROMs in the gastrointestinal tract include mucosal oxidases such as xanthine oxidase, amine oxidase, and aldehyde oxidase as well as the NADPH oxidase found in the resident phagocytic leukocytes (macrophages, neutrophils, eosinophils) of the lamina propria. We have demonstrated that reperfusion of ischemic small intestine results in substantial mucosal injury that is mediated by oxy radicals generated from xanthine oxidase and inflammatory leukocytes. The final mediator of toxicity appears to be the hydroxyl radical derived from the iron-catalyzed interaction between superoxide and hydrogen peroxide. Data from our laboratories as well as other laboratories suggest that reactive oxygen metabolites may play an important role in mediating mucosal injury during active episodes of ulcerative colitis. We present a working hypothesis which states that transient ischemic episodes in the bowel initiate a cascade of self-perpetuating cycles of ROM formation, inflammation and, ultimately, mucosal injury.
 ...
PMID:Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites. 283 Oct 16

The detergent-induced amplification of lucigenin-dependent chemiluminescence of O2-, generated by xanthine oxidase or microsomal NADPH oxidase was studied. An assay system is described which is at least 10 times more sensitive than normal lucigenin-dependent chemiluminescence due to the amplification by high concentrations of octylphenylpolyethylene glycol (Triton X-100). Compared to the superoxide dismutase-sensitive reduction of acetylated cytochrome c, a 3750-fold lower amount of microsomal protein was necessary to produce an O2- signal 10-fold above the background. In contrast to cytochrome c reduction, detergent-amplified chemiluminescence of lucigenin was completely inhibited by superoxide dismutase and therefore more selective for O2-. The membrane-bound and Triton X-100-solubilized NADPH oxidase from microsomes of macrophages was activated by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid and inhibited by Ca2+ and sodium dodecyl sulfate. The membrane-bound enzyme showed a Km value of 1.35 microM, which decreased to 0.95 microM after the addition of 12% (g/g) Triton X-100. The Km and Vmax values of soluble xanthine oxidase were not influenced by Triton X-100, indicating that the enzyme activities were not impaired by the high concentrations of detergent.
 ...
PMID:Detergent-amplified chemiluminescence of lucigenin for determination of superoxide anion production by NADPH oxidase and xanthine oxidase. 283 20

We postulated that Captopril may be capable of acting as a scavenger of free radicals, and performed in vitro studies using harvested human neutrophils. We studied the effect of Captopril on the reduction of Fe3+ cytochrome c by stimulated PMN's. Captopril acts as a reducing agent in this system, and is capable of reducing Fe3+ cytochrome c by itself. NADPH oxidase was harvested from PMA-stimulated human PMN's. Captopril inhibited the activity of this enzyme as assessed by the disappearance of NADPH determined spectrophotometrically. Since similar inhibition could be demonstrated with the superoxide scavenger superoxide dismutase, further studies were conducted using a DTNB assay of the terminal sulfhydryl group of Captopril, in the presence of a biochemical generator of superoxide (hypoxanthine/xanthine oxidase). We were unable to demonstrate disappearance of the thiol group in this system, suggesting that reaction of the SH group with 02- is unlikely under our conditions. We conclude that Captopril may interfere with human PMN NADPH oxidase in vitro.
 ...
PMID:Captopril--a potential free radical scavenger: inhibition of PMN NADPH oxidase. 284 20

The reduction of ubiquinone-5 (Q1) by the phagocytosis-specific NADPH oxidase of guinea pig macrophages was not inhibited by superoxide dismutase (SOD) at concentrations usually used for O2- assay but was inhibited at about 100-times higher concentrations. Titration of the reaction with SOD and a comparison with that of xanthine oxidase showed that the inhibition was not due to the semiquinone oxidation accelerated by a removal of O2- but due to the accelerated dismutation of O2- which otherwise reduces the quinone. Molecular oxygens are therefore preferential electron acceptors in the NADPH oxidase even in the presence of Q1.
 ...
PMID:Ubiquinone-5 is reduced by superoxide in the aerobic state by NADPH oxidase of guinea pig macrophages. 298 7

Many stimuli induce neutrophils to undergo an oxidative burst and generate toxic oxygen metabolites. The major products are O2- and H2O2, the latter being presumed to arise by spontaneous dismutation of the former. If H2O2 were indeed derived exclusively from released O2- according to the equation 2O2- + 2H+----H2O2 + O2, one would expect that relationship to be reflected in the ratio of the two metabolites detectable in the extracellular mileu of stimulated neutrophils. A second corollary is that H2O2 should not form when cytochrome c is present to scavenge O2- before it can dismutate. Although H2O2 cannot be measured directly in the presence of cytochrome c because it is consumed in reoxidizing reduced cytochrome c, its presence can be detected indirectly by the ability of catalase to improve the apparent yield of reduced cytochrome c. We found that the relative amounts of extracellular H2O2 and O2- that could be measured in the environment of stimulated neutrophils varied with the stimulus and that catalase protected reduced cytochrome c from H2O2 oxidation when some stimuli were used but not with others. For example, the ratio of O2- to H2O2 produced by neutrophils exposed to PMA was about 2:1, the expected result if H2O2 were derived from O2-. However when cytochalasin B was added to the cells before the stimulus, the yield of H2O2 was reduced but not the yield of O2-. When cells were allowed to settle and spread on tissue culture plastic they produced equimolar amounts of O2- and H2O2. Coating the plastic with IgG doubled cytochrome c reduction without effecting H2O2. In contrast, coating with albumin reduced H2O2 without effecting cytochrome c reduction. Soluble IgG aggregates induced production of mostly O2- whereas immune complexes resulted in release of both metabolites. FMLP and A23187 were similar to the soluble IgG aggregates in their effects and induced release of proportionately more O2- than H2O2. The addition of catalase to the cytochrome c solution improved the yield of reduced cytochrome c when PMA or IgG was used to stimulate the cells but not when FMLP was used. These and other data suggest that H2O2 release is not a linear function of the amount of O2- generated and that either a variable fraction of O2- spontaneously dismutates to H2O2 or the neutrophil NADPH oxidase, in a manner analogous to xanthine oxidase, is capable, under some circumstances, of producing H2O2 as well as O2-.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neutrophils may directly synthesize both H2O2 and O2- since surface stimuli induce their release in stimulus-specific ratios. 300 Sep 43

Maintenance of an acidic intralysosomal compartment may be relevant to multiple aspects of neutrophil function. The effect of lysosomal alkalinization on the neutrophil respiratory burst was studied by measuring cytochrome c reduction in response to soluble stimuli in the presence of lysosomotropic weak bases. The weak bases chloroquine, ammonium chloride, methylamine, and clindamycin all raised the intralysosomal pH and inhibited neutrophil oxidative metabolism at concentrations ranging from 0.1 to 100 mmol/L. Inhibition was dose dependent for each base and correlated significantly with the degree of lysosomal alkalinization. Concentrations that did not alkalinize the lysosome did not inhibit the respiratory burst. Inhibition by weak bases was seen when oxidative metabolism was stimulated by phorbol myristate acetate, calcium ionophore A23187, formyl-methionyl-leucyl-phenylalanine, opsonized zymosan, or sodium fluoride. Increasing the stimulus concentration (from 5 ng/mL to 5 micrograms/mL phorbol myristate acetate and from 0.5 to 1 mumol/L A23187) diminished or abolished inhibition by weak bases. Washing the cells after incubation with bases and before stimulation substantially reversed the inhibition. None of the bases impaired detection of superoxide in a cell-free xanthine-xanthine oxidase assay. Other indexes of oxidative metabolism, including oxygen consumption and hydrogen peroxide release, were also inhibited by weak bases. Analysis of particulate NADPH oxidase activity from neutrophils stimulated in the presence of bases suggested that these cells assemble a subnormal amount of an enzyme complex with normal kinetic characteristics. Lysosomotropic weak bases alkalinized the neutrophil lysosome and produced inhibition of oxidative metabolism that was dose related, was not stimulus specific, and was largely reversed by washing the cells before stimulation. A possible explanation would be altered assembly of the enzyme complex involved in respiratory burst activation as a consequence of impaired granule/plasma membrane fusion in the presence of diminished transmembrane pH gradients.
 ...
PMID:Inhibition of neutrophil oxidative metabolism by lysosomotropic weak bases. 300 23

The ratio of superoxide production to oxidation of NADPH affected by the NADPH:O2 oxidoreductase of human neutrophils is strongly influenced by pH, NADPH substrate concentration, aging of the enzyme, or its exposure to excess deoxycholate. Freshly prepared enzyme exhibited a Km for NADPH of 52 microM as determined by assaying NADPH oxidase activity, or approximately 33 microM by measurement of superoxide formation. In the range of 100-150 microM NADPH at pH 7.6 and in the presence of 0.06% deoxycholate, the univalent flux of electron equivalents given up by NADPH to O2 was 99%. Following storage of the oxidoreductase overnight on ice, its Km for NADPH rose to 125 microM as determined by monitoring oxidation of NADPH but was unaltered when measured in terms of superoxide production. Concomitantly, its capacity to affect univalent reduction of O2 fell approximately 20-30% under the same assay conditions. Univalent flux rates of less than 40% were observed with exposure of the enzyme to concentrations of deoxycholate in excess of 0.1% or to pH values below 6.0 or above 8.0. The capacity of the enzyme to carry out univalent reduction fell with increasing NADPH concentrations in a manner resembling that previously reported with increasing concentrations of xanthine in the case of xanthine oxidase (Fridovich, I. (1970) J. Biol. Chem. 245, 4053-4057). The reduced form of the neutrophil oxidoreductase, like xanthine oxidase, thus appears to be capable of conducting both 1- and 2-electron transfer steps in reducing O2. Its capacity to affect univalent reduction of O2 depends upon the concentration of electron donor (NADPH) supplied as well as conditions of storage and assay of the native enzyme.
 ...
PMID:The NADPH:O2 oxidoreductase of human neutrophils. Stoichiometry of univalent and divalent reduction of O2. 300 41

The ability of different homologues of Coenzyme Q to quench O2- was tested in vitro with three experimental systems known to generate O2-. Two of them were biological generators, namely the xanthine-xanthine oxidase system and the cyanide-insensitive NADPH oxidase of polymorphonuclear leucocytes. The third was a chemical generator of O2-, the NADH-phenazine methosulphate-nitroblue tetrazolium mixture. Short-side-chain ubiquinones were found to be the most potent scavengers of O2-, being effective at concentrations as low as 10(-7) M. This finding might be ascribed to the relatively greater water-solubility of the lower homologues of CoQ. We postulate that CoQ10 may well exert such an O2- -scavenging mechanisms in vivo where it is inserted in its natural phospholipid environment.
 ...
PMID:In vitro effect of different ubiquinones on the scavenging of biologically generated O2-. 301 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>