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)

The ability of granulocytes to generate superoxide anions (O2-) and hypochlorite (OCl-) during phagocytosis was investigated using peripheral blood samples from adults and cord blood samples from neonates, using the chemiluminescence probe cypiridina luciferin analog (CLA) for O2- generation and luminol (L) for OCl- generation. OCl- generation by granulocytes was also monitored by taurine chloramine formation. The chemiluminescence probe based upon CLA was highly specific for and sensitive to O2- and could be adopted to determine O2- generation in terms of xanthine oxidase units. The CLA-dependent chemiluminescence by cord blood granulocytes was significantly higher than that by normal adult granulocytes. Taurine chloramine formation was significantly correlated with the L-dependent chemiluminescence (L-CL). Thus, the L-CL is considered to be mainly involved in OCl- generated by phagocytizing granulocytes. L-CLs by cord blood granulocytes and normal adult granulocytes were essentially the same during phagocytosis.
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PMID:The ability of granulocytes to generate superoxide anions and hypochlorite during phagocytosis: comparison of neonatal granulocytes with adult granulocytes. 217 58

The specific thiol protease inhibitor, NCO-700, which is related to L-trans-epoxysuccinylpeptides, inhibited oxidant production by chemoattractant-stimulated rabbit polymorphonuclear leukocytes. NCO-700 could also scavenge active oxygen generated from sodium hypochlorite-hydrogen peroxide and hypoxanthine-xanthine oxidase systems.
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PMID:Effect of NCO-700, an inhibitor of thiol protease, on reactive oxygen production by chemotactic peptide-stimulated rabbit peripheral granulocytes. 283 17

Examination of the spectra of phagocytosing neutrophils and of myeloperoxidase present in the medium of neutrophils stimulated with phorbol myristate acetate has shown that superoxide generated by the cells converts both intravacuolar and exogenous myeloperoxidase into the superoxo-ferric or oxyferrous form (compound III or MPO2). A similar product was observed with myeloperoxidase in the presence of hypoxanthine, xanthine oxidase and Cl-. Both transformations were inhibited by superoxide dismutase. Thus it appears that myeloperoxidase in the neutrophil must function predominantly as this superoxide derivative. MPO2 autoxidized slowly (t 1/2 = 12 min at 25 degrees C) to the ferric enzyme. It did not react directly with H2O2 or Cl-, but did react with compound II (MP2+ X H2O2). MPO2 catalysed hypochlorite formation from H2O2 and Cl- at approximately the same rate as the ferric enzyme, and both reactions showed the same H2O2-dependence. This suggests that MPO2 can enter the main peroxidation pathway, possibly via its reaction with compound II. Both ferric myeloperoxidase and MPO2 showed catalase activity, in the presence or absence of Cl-, which predominated over chlorination at H2O2 concentrations above 200 microM. Thus, although the reaction of neutrophil myeloperoxidase with superoxide does not appear to impair its chlorinating ability, the H2O2 concentration in its environment will determine whether the enzyme acts primarily as a catalase or peroxidase.
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PMID:Production of the superoxide adduct of myeloperoxidase (compound III) by stimulated human neutrophils and its reactivity with hydrogen peroxide and chloride. 299 50

Arachidonic acid is converted to 12-hydroxyeicosatetraenoic acid (12-HETE) in a homogenate of mouse epidermal cells. When the epidermal homogenate was preincubated with scavengers of reactive oxygen species (ROS), catalase or superoxide dismutase, significantly larger amounts of 12-HETE were produced as compared to untreated controls, suggesting that 12-lipoxygenase is quite prone to inactivation by ROS and peroxides. Mouse epidermal homogenate was then exposed to nine different ROS-generating systems to study the effects of superoxide, hydrogen peroxide, singlet oxygen, hypochlorite, peroxyl radicals, and alkyl hydroperoxides on the enzyme activity. Analysis by chiral phase high performance liquid chromatography demonstrated that the 12-HETE biosynthesized from arachidonic acid by mouse epidermal homogenate was the 12 (S)-enantiomer and excludes oxidation of arachidonic acid by ROS in a nonspecific free radical mechanism which leads to racemic 12-HETE. ROS generated by the interaction of xanthine with xanthine oxidase strongly inhibited epidermal 12 (S)-HETE biosynthesis. A flux of 0.7 nmol of superoxide/min/ml of reaction medium resulted in more than 50% inhibition of epidermal 12-lipoxygenase activity. The decrease in 12 (S)-HETE biosynthesis appeared to involve both superoxide and hydrogen peroxide. The efficacy of the latter species was also documented by exposure of mouse epidermal 12-lipoxygenase to glucose and glucose oxidase, which resulted in similar inhibitory effects on 12 (S)-HETE biosynthesis. The presence of the iron chelator diethylenetriaminepentaacetic acid during incubation of epidermal 12-lipoxygenase with both the xanthine/xanthine oxidase or the glucose/glucose oxidase systems partially protected the enzyme against inhibition, indicating that hydroxyl radical contributes to the overall inhibitory effect. Also, organic hydroperoxides inhibited epidermal 12-lipoxygenase, whereas singlet oxygen, hypochlorite, and peroxyl radicals were not effective. The results of this study lead to the proposal that 12-lipoxygenase activity may be regulated by ROS such as hydrogen peroxides, superoxide, and hydroxyl radicals.
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PMID:Effects of reactive oxygen species on the biosynthesis of 12 (S)-hydroxyeicosatetraenoic acid in mouse epidermal homogenate. 919 95

Previous studies from our laboratory have shown that nitric oxide (NO) can reduce the release of free radicals from activated leukocytes. The aim of this study was to assess the role of endothelium-derived nitric oxide and leukocyte-derived free radicals in the contractile response to non-preactivated leukocytes. Vessel tension studies were performed in rabbit endothelium-intact aortic vessel rings precontracted with 5-hydroxytryptamine (1 microM). Addition of leukocytes isolated from rabbit blood were added to the rings in increasing concentrations (10(3)-10(6) cell ml(-1)) under control conditions and in the presence of L-nitroarginine methyl ester (L-NAME 1 mM), D-NAME (1 mM), or superoxide dismutase (100 U ml(-1)). The responses to superoxide radical (generated by xanthine plus xanthine oxidase, X/XO), hydrogen peroxide, hypochlorite and peroxynitrite were also assessed. The nature of the free radicals released from non-activated isolated leukocytes, zymosan-stimulated leukocytes (in whole blood) and isolated vessel rings was assessed using luminol-enhanced chemiluminescence. Cumulative addition of leukocyte suspensions to aortic rings caused a concentration-dependent contractile response which was abolished by preincubation of the vessel ring with L-NAME. D-NAME and superoxide dismutase were without effect. All the free radicals tested produced a relaxation of the precontracted aortic ring. The response to X/XO was not affected by superoxide dismutase, but abolished by catalase. The responses to hydrogen peroxide and hypochlorite were both found to be dependent upon the presence of endothelium and NO. The response to peroxynitrite was endothelium-independent and was blocked by methylene blue. While the main free radical released from unstimulated leukocytes and vessel rings was superoxide, the main radical released from activated leukocytes was found to be hypochlorite. These results suggest that the vascular contraction seen in response to non-preactivated leukocytes is due to inhibition, by NO, of the release of free radicals from the leukocytes when activated by contact with the vascular endothelium, thus allowing co-released vasoconstrictor substances to exert their effect.
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PMID:Role of nitric oxide and free radicals in the contractile response to non-preactivated leukocytes. 959 26

5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is developed as a therapeutic agent for ulcerative colitis. To clarify its mechanism of action, the effects of BX661A and its metabolites 5-aminosalicylic acid (5-ASA) and 4-aminobenzoyl-beta-alanine (4-ABA) on reactive oxygen species: superoxide radicals (O2-) generated by hypoxanthine and xanthine oxidase, hydrogen peroxide (H2O2), hypochlorite radicals (OCl-) and hydroxyl radicals (OH.), were investigated and compared with the effects of 2-hydroxy-5-[[4-[(2-pyridinylamino)sulfonyl]phenyl]azo]-benzoic acid (CAS 599-79-1, salazosulfapyridine, SASP) and its metabolite 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP). 1. BX661A, SASP and 5-ASA inhibited O2- radical production in a concentration-dependent manner (IC50 = 0.14, 0.13 and 0.19 mmol/l, respectively). The effects of 4-ABA and SP on O2- radical production were weak (IC50 = > 10 and > 3 mmol/l, respectively). In contrast, superoxide dismutase inhibited O2- radical production in a concentration-dependent manner (IC50 = 1.7 U/ml). 2. BX661A, SASP, 4-ABA and SP had no H2O2 scavenging effects. 5-ASA scavenged H2O2, but its maximal scavenging action was 51.3%. In contrast, catalase scavenged H2O2 in a concentration-dependent manner (IC50 = 0.47 U/ml). 3. BX661A, SASP and 5-ASA scavenged OCl- radicals in a concentration-dependent manner (IC50 = 69.5, 73.8 and 21.7 mumol/l, respectively). 4-ABA and SP had no OCl- radical scavenging effects. In contrast, nordihydroguaiaretic acid (NDGA) scavenged OCl- radicals in a concentration-dependent manner (IC50 = 8.7 mumol/l). 4. BX661A and SASP scavenged OH. radicals in a concentration-dependent manner; the maximal scavenging values were 39.5 (10 mmol/l) and 48.6% (3 mmol/l), respectively. 4-ABA and SP had no OH. radical scavenging effects. In contrast, 5-ASA scavenged OH. radical in a concentration-dependent manner (IC50 = 1.46 mmol/l). These results suggest that BX661A has O2- and OCl- radical scavenging effects and that 5-ASA has O2-, OCl- and OH. radical scavenging effects. Therefore, these effects may be partially involved in the therapeutic effects of BX661A on ulcerative colitis.
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PMID:Effects of BX661A, a new therapeutic agent for ulcerative colitis, on reactive oxygen species in comparison with salazosulfapyridine and its metabolite sulfapyridine. 982 18

Two kinds of chemiluminescent microspheres were prepared as tools for measuring reactive oxygen species (ROS) released into phagosomes in phagocytizing cells, by chemically binding acridinium ester or ABEI (isoluminol derivative) to polymer microspheres, and were examined from the viewpoint of specificity and sensitivity to ROS. Acridinium ester-bound microspheres (AE-ms) were found to be a sensitive probe to superoxide anion and hydrogen peroxide under a neutral condition (pH 7.2). AE-ms emitted strong chemiluminescence (CL) by hypoxanthine (HPX)/xanthine oxidase (XOD) or hydrogen peroxide. The CL by HPX/XOD was initially inhibited by superoxide dismutase. At pH 5.6, the CL intensity from AE-ms in the presence of HPX/XOD was reduced to about one-eighth of that at pH 7.2. ABEI-bound microspheres (ABEI-ms) were found to be a selective probe for singlet oxygen although not highly sensitive. ABEI-ms emitted CL of moderate intensity with hydrogen peroxide/myeloperoxidase (MPO), but not with hydrogen peroxide alone or with hypochlorite/MPO at pH 5.6. The CL from ABEI-ms with hydrogen peroxide/MPO was completely inhibited by azide. ABEI-ms did not emit CL in the presence of HPX/XOD or by potassium superoxide at pH 5.6. The result of supplemental experiments using dissolved chemiluminescent probes and non-enzymatically generated ROS supported the above-described selectivity and sensitivity of chemiluminescent microspheres.
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PMID:Selectivity and sensitivity in the measurement of reactive oxygen species (ROS) using chemiluminescent microspheres prepared by the binding of acridinium ester or ABEI to polymer microspheres. 1060 7

Hyperlipoproteinemia can aggravate glomerulosclerosis and chronic tubulointerstitial (ti) damage in kidneys without primary immunologic disease. We evaluated whether the effect of hyperlipidemia on progression of renal damage differed between kidneys without preexisting glomerular disease and kidneys with mesangioproliferative glomerulonephritis and whether the renal actions of hyperlipidemia were dependent on oxidant-antioxidant balance. Hyperlipidemia was induced by high-fat and high-cholesterol diet in uninephrectomized rats. In rats without glomerulonephritis, hyperlipidemia led to a rise in glomerular and ti generation of reactive oxygen species (ROS). Oxygen radicals were mainly generated by enhanced xanthine oxidoreductase (XO), which rose with protein concentration and activity during hyperlipidemia; concurrently, glomerulosclerosis and chronic ti injury were noticed during hyperlipidemia [ti damage (% of total tubulointerstitium (TI) after 150 days): normolipidemia 0.1 +/- 0% vs. hyperlipidemia 3.4 +/- 0. 9%; P < 0.05]. In mesangioproliferative Thy-1 nephritis, ti injury was significantly accelerated by hyperlipidemia (ti damage after 150 days: normolipidemic Thy-1 nephritis 2.5 +/- 0.6% vs. hyperlipidemic Thy-1 nephritis 12.5 +/- 3.1%; P < 0.05). Antioxidant enzyme activities decreased and XO activity rose markedly in the TI (XO activity in TI after 150 days: normolipidemic Thy-1 nephritis 2.2 +/- 0.5 vs. hyperlipidemic Thy-1 nephritis 4.5 +/- 0.7 cpm/microg protein; P < 0.05). In hyperlipidemic Thy-1 nephritis rats, which had a higher urinary protein excretion than normolipidemic rats, hypochlorite-modified proteins, an indirect measure for enhanced myeloperoxidase activity, were detected in renal tissue and in urine, respectively. During hyperlipidemia, chronic damage increased in renal TI. Enhanced generation of ROS, rise in oxidant enzyme activity, and generation of hypochlorite-modified proteins in renal tissue and urine were noticed. These data suggest that oxidant stress contributed to the deleterious effects of hyperlipidemia on the renal TI.
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PMID:Oxidant stress in hyperlipidemia-induced renal damage. 1064 56

We studied the interactions of isolated equine neutrophils with endothelial cells in culture, mimicking a situation of acute inflammation. Our main purpose was to demonstrate that the supernatant of activated neutrophils was sufficient to damage endothelial cells. Equine endothelial cells (from carotid arteries) were covered either with increased numbers of equine neutrophils stimulated by phorbol myristate acetate, or with the supernatant collected after an in vitro stimulation of the neutrophils. Cytotoxicity was estimated by the release of preincorporated 51Cr, and by light microscopy observations. To assert the specific role of reactive oxygen species, endothelial cells were treated by the hypoxanthine/xanthine oxidase (X/XOx) system (production of superoxide anion and hydrogen peroxide), and by hypochlorite (product of the activity of myeloperoxidase). A strong cytotoxicity was found with stimulated neutrophils; microscopic observations indicated a loss of 50% of the endothelial cells and morphological alterations in the remaining cells. The supernatant of stimulated neutrophils was cytotoxic, in correlation with the number of neutrophils used to obtain the supernatant, and with the supernatant concentration of myeloperoxidase. The cytotoxicity of the X/XOx system was weak, but was increased by myeloperoxidase. Hypochlorite was highly toxic. We concluded that the supernatant of stimulated neutrophils was sufficient to obtain cytotoxic effects on the endothelium, in the absence of a direct contact between endothelium and neutrophils, and that this cytotoxicity was mainly linked to the activity of myeloperoxidase. From these in vitro results, it can be extrapolated that in pathologies characterised by an important activation of neutrophils, damage can spread to cells and tissues away from the inflammation focus.
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PMID:Cytotoxicity of stimulated equine neutrophils on equine endothelial cells in culture. 1095 82

A new family of tridentate ligands PhimpH (2-((2-phenyl-2-(pyridin-2-yl)hydazono)methyl)phenol), N-PhimpH (2-((2-phenyl-2-(pyridin-2-yl)hydrazono)methyl)napthalen-1-ol), Me-PhimpH (2-(1-(2-phenyl-2-(pyridine-2-yl)hydrazono)ethyl)phenol) have been synthesized and characterized. The ligands PhimpH and N-PhimpH after deprotonation react with manganese(II) and manganese(III) starting materials affording [Mn(Phimp)(2)] (1), [Mn(Phimp)(2)](ClO(4)) (2), [Mn(N-Phimp)(2)] (3), [Mn(N-Phimp)(2)](ClO(4)) (4). Complexes [Mn(Phimp)(2)] (1) and [Mn(N-Phimp)(2)] (3) convert to [Mn(Phimp)(2)](+) (cation of 2) and [Mn(N-Phimp)(2)](+) (cation of 4) respectively upon oxidation. Ligand Me-PhimpH stabilized only manganese(III) centre resulting [Mn(Me-Phimp)(2)](ClO(4)) (5). The molecular structures of [Mn(Phimp)(2)], 1 and [Mn(Phimp)(2)](ClO(4)), 2 were determined by single crystal X-ray diffraction. X-ray crystal structures of 1 and 2 have revealed the presence of distorted octahedral MnN(4)O(2) coordination sphere having meridionally spanning ligands. Electrochemical studies for the complexes showed Mn(II)/Mn(III), (E(1/2)=0.14-0.40V) and Mn(III)/Mn(IV), (E(1/2)=0.80-1.06V) couples vs. Ag/AgCl. The redox properties were exploited to examine superoxide dismutase (SOD) activity using Mn(II)/Mn(III) couple. The complexes 1, 2, 4 and 5 have been revealed to catalyze effectively the dismutation of superoxide (O(2)(.-)) in xanthine-xanthine oxidase-nitro blue tetrazolium assay and IC(50) values were found to be 0.29, 0.39, 1.12 and 0.76 microM respectively. DNA interaction studies with complex 2 showed binding of DNA in a non-intercalative pathway. Complexes 1, 2 and 4 exhibited nuclease activity in presence of H(2)O(2) and inhibition of activity was noted in presence of KI.
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PMID:Stabilization of Mn(II) and Mn(III) in mononuclear complexes derived from tridentate ligands with N2O donors: synthesis, crystal structure, superoxide dismutase activity and DNA interaction studies. 1987 75


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