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)

Interactions between rat pulmonary artery endothelial cells and hydrogen peroxide or toxic oxygen products from phorbol ester-activated human neutrophils result in endothelial cell killing defined by 51Cr release. It has been shown that this cytotoxic reaction can be blocked by the presence of catalase, iron chelators, or scavengers of the hydroxyl radical. Evidence shows that products from xanthine oxidase of endothelial cells are necessary for the toxic effects of hydrogen peroxide or phorbol ester-activated neutrophils. Addition of xanthine oxidase inhibitors protects against phorbol ester-mediated injury of endothelial cells. Preloading of endothelial cells with superoxide dismutase attenuates injury caused either by hydrogen peroxide or phorbol ester-activated neutrophils. Conversion of xanthine dehydrogenase to xanthine oxidase in endothelial cells occurs during contact of endothelial cells by activated neutrophils. This conversion is not related to oxygen products of neutrophils. Conversion of xanthine dehydrogenase to xanthine oxidase in endothelial cells is also induced by endothelial cell contact with C5a, N'-formyl-methionyl-leucyl-phenylalanine (fMLP), or tumor necrosis factor alpha (TNF alpha). Interaction of hydrogen peroxide with endothelial cells rapidly depletes adenosine triphosphate (ATP) and causes the extracellular appearance of xanthine and hypoxanthine. Agents that protect endothelial cells from the toxic effects of hydrogen peroxide do not prevent falls in cellular ATP caused by hydrogen peroxide, indicating that ATP levels do not necessarily correlate with cytotoxic events. A synergy between hydrogen peroxide and proteases in endothelial cell killing has been demonstrated. TNF alpha causes alterations in endothelial cells, the result of which is increased susceptibility to killing by PMA-activated neutrophils.
Am J Med 1991 Sep 30
PMID:Mechanisms of endothelial cell killing by H2O2 or products of activated neutrophils. 192 18

Circulating antibodies to whole dried cows' milk, previously reported to be elevated in patients with myocardial infarction, have been shown to be directed mainly to the bovine milk fat globule membrane. Human antibodies against the bovine milk fat globule membrane themselves interact primarily with the enzyme, xanthine oxidase. Comparison of anti-(xanthine oxidase) antibody levels in 107 patients, who had suffered a myocardial infarction, with those in 86 control subjects showed significantly higher IgM levels in the patients with myocardial infarction. No corresponding differences were found for IgG or IgA anti-(xanthine oxidase) antibodies. Total levels of IgM class immunoglobulins did not differ between patients and controls. Serial assays following myocardial infarction showed no evidence that raised levels of IgM anti-(xanthine oxidase) antibodies result from the infarction itself.
Cardioscience 1990 Sep
PMID:Antibodies to xanthine oxidase: elevated levels in patients with acute myocardial infarction. 210 7

Damage to the bases in DNA by the cupric ion-1,10-phenanthroline complex was investigated. Ten base products in DNA were identified and quantitated by the use of gas chromatography/mass spectrometry with selected-ion monitoring. DNA damage by the cupric ion-1,10-phenanthroline complex required the presence of a reducing agent such as ascorbic acid or mercaptoethanol. Products identified were typical hydroxyl radical induced products from the pyrimidines and purines in DNA, well-known from previous studies using various hydroxyl radical producing systems such as ionizing radiation, hypoxanthine/xanthine oxidase, or hydrogen peroxide in the presence of transition metal ions. Product formation was not significantly inhibited by typical scavengers of hydroxyl radical such as mannitol and sodium formate, but there was partial inhibition by dimethyl sulfoxide. Catalase substantially decreased formation of base products, and added hydrogen peroxide stimulated it, indicating the hydrogen peroxide dependency of DNA base damage. Superoxide dismutase afforded only a partial reduction in product yields in systems containing ascorbic acid. On the basis of the types of base products formed, the hydrogen peroxide dependency of product formation, and a previous report suggesting that DNA damage is due to a diffusible species [Williams, L. D., Thivierge, J., & Goldberg, I. H. (1988) Nucleic Acids Res. 16, 11607-11615], we propose that DNA base damage is caused by hydroxyl radical.
Biochemistry 1990 Sep 11
PMID:Modification of bases in DNA by copper ion-1,10-phenanthroline complexes. 212 17

Ventricular myocytes from neonatal Wistar rats were cultured with 80% Dulbecoo's modified Eagle medium and 20% fetal bovine serum. An appropriate amount of xanthine and xanthine oxidase was added to the culture medium to increase the content of free radicals in cardiac cells. Variation in action potential and input impedance of cardiac myocytes indicated the oxidative damage to the membrane. The ultrastructure of heart cells, characteristically the myofilaments and mitochondria, was damaged. Electron spin resonance measurement demonstrated that xanthine and xanthine oxidase elevated the free radical content, while selenium (Se) and manganese (Mn) reduced the free radicals in cultured heart cells. Supplementation of 0.173 microgram/ml Se and 0.1 microgram/ml Mn into the culture medium separately or simultaneously antagonized the damage induced by xanthine and xanthine oxidase. The possible mechanism might be the production of superoxide anion free radical leading to free radical damage to cardiac cells. Se and Mn might play a role as scavengers through glutathione peroxidase and superoxide dismutase respectively and thus protect cardiac cells from free radical damage.
Chin Med J (Engl) 1990 Sep
PMID:Protective action of selenium and manganese on xanthine and xanthine oxidase induced oxidative damage to cultured heart cells. 212 74

Oxygen-derived free radicals have been implicated in damage to membrane phospholipids leading to alterations in membrane function. The purpose of this study was to investigate alterations in intracellular ionic calcium (Ca2+) levels and Ca2+ transients, cellular morphology, conjugated diene levels, arachidonate release, and lactate dehydrogenase release resulting from the exposure of cultured neonatal rat ventricular myocytes to a xanthine oxidase catalyzed free radical generating system capable of producing superoxide and hydroxyl radicals. The ability of alpha-tocopherol to prevent alterations due to free radical exposure was investigated. For measurements of Ca2+, myocytes grown on coverslips for 3-4 days were loaded with fura-2/AM and studied by microspectrofluorometry. Control myocytes superfused with a physiological buffer or buffer containing purine and iron-loaded transferrin exhibited Ca2+ transients associated with spontaneous contractions. For control, buffer perfused myocytes (n = 4), the fura-2 340/380 ratios were 0.5 +/- 0.1 (mean +/- S.E.) and 1.6 +/- 0.03 at the minimum and maximum, respectively, of the Ca2+ transient, after 1 h of perfusion. Exposure to the free radical generating solution (n = 14) altered intracellular Ca2+. The 340/380 minimum ratio was 639% of the control value after approximately 30-70 mins with cessation of normal Ca2+ transients. Bleb development was associated with increased Ca2+. Myocytes reperfused with control medium continued to exhibit an elevated minimum fura-2 ratio at 687% of control. Myocytes pretreated with 10 microM alpha-tocopherol (n = 13) for 18-24 h and exposed to free radicals did not exhibit increases in intracellular Ca2+, having a minimum 340/380 ratio of 0.5 +/- 0.1 after 60-90 mins, and although myocytes often ceased contracting, they resumed spontaneous Ca2+ transients with control medium reperfusion and also maintained normal structure. Exposure of myocyte cultures to free radical generating solutions resulted in increased levels of conjugated dienes and increased release of [3H]arachidonate and lactate dehydrogenase compared to control values after 1 h. alpha-Tocopherol treatment attenuated the increase in conjugated diene levels, and the release of [3H]arachidonate and lactate dehydrogenase. Thus, free radicals alter intracellular Ca2+, conjugated dienes and membrane structure indicating their ability to induce altered ionic homeostasis in association with myocardial membrane damage. alpha-Tocopherol decreased free radical mediated injury.
J Mol Cell Cardiol 1990 Sep
PMID:Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. 212 94

On the basis of recent reports that the proportion of linoleic acid (C18:2Cis 9,12), a free fatty acid, is markedly decreased in acne comedones and that tetracycline is effective against acne comedones by acting directly as an antioxidant on infiltrating neutrophils, we investigated the effect of linoleic acid on several inflammatory parameters of neutrophils, including neutrophil chemotaxis, phagocytosis, and generation of reactive oxygen species (ROS). Linoleic acid significantly decreased phagocytosis and the generation of O2-, H2O2, and OH.by neutrophils, whereas it did not significantly inhibit neutrophil chemotaxis or decrease the ROS levels generated in a cell-free, xanthine-xanthine oxidase system. The present study seems to suggest that decreased levels of linoleic acid in acne comedones contribute, in part, to the worsening of acne inflammation by the failure of low levels of linoleic acid to suppress neutrophil phagocytosis and ROS generation.
J Invest Dermatol 1990 Sep
PMID:Suppressive effects of linoleic acid on neutrophil oxygen metabolism and phagocytosis. 214 21

We evaluated the role of oxygen free radicals in the induction of acute stress gastric ulcer in rats. After 12 hr of immobility, ulcers of up to 4 mm were observed in the gastric mucosa. Pretreatment with allopurinol, a xanthine oxidase inhibitor, produced a significant reduction in the number and size of lesions (p < 0.0001). No protection was afforded by aluminum hydroxide or ranitidine alone, but enhanced protection was observed when given in association to allopurinol. A secondary role for H ions is suggested by these findings. Our results support the hypothesis of a role of oxygen free radicals in the pathogenesis of stress gastric ulcers. Allopurinol might be used in conditions predisposing to stress in patients.
Rev Med Chil 1990 Sep
PMID:[The etiopathogenesis of the acute stress ulcer. The role of oxygen free radicals]. 215 40

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.
Arch Biochem Biophys 1990 Sep
PMID:Are quinones producers or scavengers of superoxide ion in cells? 216 57

The ability of various reactive oxygen species and serine proteases to activate latent collagenase (matrix metalloproteinase-1) purified from human neutrophils was examined. Latent 70-75 kD human neutrophil collagenase (HNC) was efficiently activated by known non-proteolytic activators phenylmercuric chloride (an organomercurial compound) and gold thioglucose (Au(I)-salt). Corresponding degree of activation was achieved by reactive oxygen species including hypochlorous acid (HOCl), hydrogen peroxide (H2O2) and hydroxyl radical generated by hypoxanthine/xanthine oxidase (HX/XAO). The presence of trace amounts of iron and EDTA were necessary and even enhanced H2O2 induced activation of latent HNC. This activation could be abolished by an iron chelator desferrioxamine and a hydroxyl radical scavenger mannitol. HOCl induced activation of latent HNC was not affected by desferrioxamine and mannitol. Thus, these compounds do not inhibit the active/activated form of HNC. Latent HNC could also be activated by trypsin and chymotrypsin but not by plasmin and plasma kallikrein. The ability of mannitol and desferrioxamine to inhibit the H2O2-induced activation of HNC suggests the transition metal dependent Fenton reaction to be responsible for localized and/or site-specific generation of hydroxyl radical/hydroxyl radical -like oxidants to act as the activating oxygen species. Our results support the ability of myeloperoxidase derived HOCl to act as a direct oxidative activator of HNC and further suggest the existence of a new/alternative oxidative activation pathway of HNC involving hydroxyl radical.
Biochem Biophys Res Commun 1990 Sep 28
PMID:Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteases. 217 13

The effect of isotopic substitution of the 8-H of xanthine (with 2H and 3H) on the rate of oxidation by bovine xanthine oxidase and by chicken xanthine dehydrogenase has been measured. V/K isotope effects were determined from competition experiments. No difference in H/T(V/K) values was observed between xanthine oxidase (3.59 +/- 0.1) and xanthine dehydrogenase (3.60 +/- 0.09). Xanthine dehydrogenase exhibited a larger T/D(V/K) value (0.616 +/- 0.028) than that observed for xanthine oxidase (0.551 +/- 0.016). Observed H/T(V/K) values for either enzyme are less than those H/T(V/K) values calculated with D/T(V/K) data. These discrepancies are suggested to arise from the presence of a rate-limiting step(s) prior to the irreversible C-H bond cleavage step in the mechanistic pathways of both enzymes. These kinetic complexities preclude examination of whether tunneling contributes to the reaction coordinate for the H-transfer step in each enzyme. No observable exchange of tritium with solvent is observed during the anaerobic incubation of [8-3H]xanthine with either enzyme, which suggests the reverse commitment to catalysis (Cr) is essentially zero. With the assumption of adherence to reduced mass relationships, the intrinsic deuterium isotope effect (Dk) for xanthine oxidation is calculated to be 7.4 +/- 0.7 for xanthine oxidase and 4.2 +/- 0.2 for xanthine dehydrogenase. By use of these values and steady-state kinetic data, the minimal rate for the hydrogen-transfer step is calculated to be approximately 75-fold faster than kcat for xanthine oxidase and approximately 10-fold faster than kcat for xanthine dehydrogenase. This calculated rate is consistent with data obtained by rapid-quench experiments with XO. A stoichiometry of 1.0 +/- 0.3 mol of uric acid/mol of functional enzyme is formed within the mixing time of the instrument (5-10 ms). The kinetic isotope effect data also permitted the calculation of the Kd values [Klinman, J. P., & Mathews, R. G. (1985) J. Am. Chem. Soc. 107, 1058-1060] for substrate dissociation, including all reversible steps prior to C-H bond cleavage. Values calculated for each enzyme (Kd = 120 microM) were found to be identical within experimental uncertainty.
Biochemistry 1990 Sep 25
PMID:Kinetic isotope effect studies on milk xanthine oxidase and on chicken liver xanthine dehydrogenase. 227 76


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