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

---

Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous reports indicate that intestinal intraluminal ethanol increases mucosal permeability (an index of mucosal injury) and histamine release by mast cells, and that the released histamine plays a role in mediating the increased permeability. In the present study, we investigated whether reactive oxygen metabolites and their major sources (xanthine oxidase and leukocytes) were involved in these ethanol effects. In rabbits, segments of the jejunum were perfused with a control solution or with 6% ethanol. In these segments, mucosal permeability was assessed by determining jejunal clearance of i.v. administered 51Cr-ethylenediaminetetraacetate (51Cr-EDTA) and 125I-bovine serum albumin (125I-BSA), and mast cell histamine release was estimated from the histamine concentration of the gut effluent. Ethanol increased 51Cr-EDTA clearance, 125I-BSA clearance, and histamine release. These ethanol effects decreased when the animals were given superoxide dismutase plus catalase (scavenger of O2- and H2O2, respectively), allopurinol, or oxypurinol (xanthine oxidase inhibitors). Administration of a monoclonal antibody (R15.7) against leukocyte adhesion molecule, CD18, inhibited completely the ethanol-induced increased 51Cr-EDTA and 125I-BSA clearances and histamine release. These and supplementary data suggest that (a) ethanol-induced mucosal injury and mast cell histamine release are mediated primarily by leukocytes, and (b) oxy radicals, especially those generated by xanthine oxidase, mediate these ethanol effects mainly by promoting leukocyte infiltration.
...
PMID:Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced jejunal mucosal injury. 901 59

8-(3-Methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one (BOF-4272) blocks xanthine oxidase/xanthine dehydrogenase in the liver. BOF-4272 with a sulfoxide chiral center includes R(+)- and S(-)-enantiomers. The enantioselectivity in the global disposition of BOF-4272 can be attributed to that in the local disposition of organs, especially the liver. Thus, the enantioselectivity in the hepatic local disposition of BOF-4272 was compared between R- and S-enantiomers by a hepatic perfusion experiment with a pulse input into the portal vein. The influence of perfusate albumin on the enantioselective local disposition was also investigated. The elution time profile of each BOF-4272 enantiomer from the liver into the hepatic vein was measured at four different bovine serum albumin (BSA) concentrations (0, 0.25, 1.0 and 4.0%) in the perfusate at 37 and 4 degrees C. A crossover test was carried out for R- and S-enantiomers using one rat liver. In the absence of perfusate BSA at 37 degrees C, hepatic extraction ratios (E[H]) of R- and S-enantiomers of BOF-4272 were 75.6 +/- 4.3% and 71.7 +/- 3.3%, respectively, which were statistically the same. In the presence of 4.0% BSA at 37 degrees C, E(H) values of R- and S-enantiomers were 31.7 +/- 4.6% and 19.6 +/- 3.8%, respectively, which demonstrated that E(H) of R-enantiomer was significantly greater than that of S-enantiomer (p < 0.001). In the absence and presence of perfusate BSA at 4 degrees C, there was no significant difference in E(H) between S- and R-enantiomers. An amplification of stereoselectivity with albumin was observed by the perfusion experiment using BOF-4272 enantiomers.
...
PMID:Influence of albumin on enantioselective local disposition of BOF-4272, a xanthine oxidase inhibitor with chiral sulfoxide, in rat liver. 944 5

Nitric oxide (.NO) and peroxynitrite (ONOO-) inhibit enzymes that depend on metal cofactors or oxidizable amino acids for activity. Since xanthine oxidase (XO) is a 2(2Fe2S) enzyme having essential sulfhydryl groups linked with Mo-pterin cofactor function, the influence of .NO and ONOO- on purified bovine XO was determined. Physiological (</=1 microM) and supraphysiological (</=100 microM) concentrations of dissolved .NO gas did not inhibit the catalytic activity or alter the spectral characteristics of XO at 25 degreesC and pH 7.0, differing from reports showing XO inhibition by .NO. The apparent decrease in XO activity observed previously was the result of depressed rates of uric acid accumulation in XO assay systems, due to ONOO--mediated oxidation of uric acid upon reaction of residual .NO with XO-derived superoxide (O*-2). Nitric oxide derived from S-nitrosoglutathione also did not inhibit cultured vascular endothelial cell XO activity. In contrast, purified and vascular endothelial cell catalase, a heme enzyme reversibly inhibited by .NO, was inhibited by similar concentrations and rates of production of . NO. In contrast to .NO, ONOO- inhibited XO (0.2 microM, 50 mU/ml) with an IC50 of 57 microM (for 3 microM/min infusion of ONOO-) or 120 microM (for bolus addition of ONOO-). Addition of 1% bovine serum albumin, 50 microM xanthine, or 10 microM uric acid protected XO from inactivation by ONOO-. Thus, in the presence of purine substrates and other more readily oxidized components of the biological milieu, XO should not be inhibited by either .NO or ONOO-. These observations reveal that .NO will not serve as an indirect antioxidant by inhibiting XO-derived production of reactive species and that the XO-derived products O*-2 and uric acid readily modify the reactivities of .NO and ONOO-.
...
PMID:Xanthine oxidase reaction with nitric oxide and peroxynitrite. 964 60

Recently published evidence indicates that polynitroxylated albumin (PNA) protects tissues against ischemia/reperfusion (I/R) injury, possibly by enhancing tissue redox activity. The objective of this study was to determine if PNA treatment alters the leukocyte-endothelial cell adhesion that is normally elicited by I/R. PNA, human serum albumin (HSA) or saline were administered (i.v.) 5 min before reperfusion. Venular diameter, red blood cell velocity, wall shear rate, systemic hematocrit, systemic arterial pressure, as well as the number of adherent and emigrated leukocytes were monitored in rat mesenteric venules before and after 20 min of ischemia and 30 min of reperfusion. In saline-treated rats, I/R elicited a 5.3-fold increase in leukocyte adhesion and a 1.8-fold increase in leukocyte emigration. HSA-treated animals exhibited 4.0 and 2.3-fold increases in leukocyte adherence and emigration, respectively. In PNA-treated rats, the number of adherent leukocytes increased only 2.1-fold increase in adherent leukocytes, while leukocyte emigration was completely inhibited. The PNA-induced attenuation of leukocyte adherence/emigration could not be attributed to alterations in systemic or local hemodynamics (red blood cell velocity or wall shear rate). PNA was also shown to be a potent inhibitor of xanthine-xanthine oxidase mediated adhesion of human neutrophils to cultured human endothelial cells. These findings indicate that PNA may protect tissues against I/R injury by attenuating leukocyte-endothelial cell adhesion.
...
PMID:Pretreatment with polynitroxyl albumin (PNA) inhibits ischemia-reperfusion induced leukocyte-endothelial cell adhesion. 966 90

It has been shown that erythrocyte membrane proteins become susceptible to degradation by membrane-bound serine protease activity after oxidative modification of the membranes (M. Beppu, M. Inoue, T. Ishikawa, K. Kikugawa, Biochim. Biophys. Acta 1196 (1994) 81-87). The aim of the present study was to clarify the presence of the serine protease in oxidized erythrocyte membranes and to characterize the selectivity of the enzyme to oxidized proteins. Human erythrocytes were oxidized in vitro with xanthine/xanthine oxidase/Fe(III) and oxidized membranes isolated. Proteolytic activity of the membranes toward spectrin obtained from oxidized membranes and bovine serum albumin oxidized with H2O2/horseradish peroxidase was increased by membrane oxidation, and the degradability of the substrates was increased by substrate oxidation. The proteolytic activity was inhibited by the serine protease inhibitor diisopropyl fluorophosphate (DFP). The 72 kDa and 80 kDa proteins in the membranes were labeled by [3H]DFP when detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions and subsequent fluorography. The 72 kDa protein was found to be a serine enzyme, acetylcholine esterase. The 80 kDa protein appeared to be responsible for the degradation of oxidatively damaged proteins. The 80 kDa protein was loosely bound to membranes and readily solubilized into a 0.1% NP-40 detergent solution. The presence of the same 80 kDa protease in intact erythrocyte cytosol was suggested. The increased serine protease activity in oxidized membranes can result from the increased adherence of the cytosolic 80 kDa serine protease to the membranes due to oxidation.
...
PMID:Characterization of membrane-bound serine protease related to degradation of oxidatively damaged erythrocyte membrane proteins. 981 51

Protein carbonyls were studied in aging and exercise by immunoblot followed by one- or two-dimensional polyacrylamide gel electrophoresis using antibodies against 2,4-dinitrophenylhydrazones. Proteins of rat kidneys exhibited significant age-related increase in the amount of carbonyl while those of the brain and liver did not. Major carbonylated proteins in the kidney included serum albumin. In nematodes in which protein carbonyls increased with age, one of the carbonylated proteins was identified as vitellogenin, an egg-yolk protein. A possible biological significance of this protein present in abundance even after egg-laying stages is discussed in terms of protection against oxidative stress. Exhaustive exercise induced significant increase in the carbonylation of selected but unidentified proteins in the lung. This oxidative stress might be caused by xanthine oxidase in this tissue and hypoxanthine derived from ATP-depleted muscles. Exercise at high altitude caused higher carbonylation of the skeletal muscle proteins, most notably a protein likely to be actin, than that at sea level but no significant difference was observed in lipid peroxidation. These studies emphasize the value of immunoblot analysis of tissue protein carbonyls in a variety of situations where oxidative stress is likely involved.
...
PMID:Carbonylated proteins in aging and exercise: immunoblot approaches. 1036 Jun 80

In the vasculature, nitrosothiols derived from the nitric oxide (NO)-mediated S-nitrosation of thiols play an important role in the transport, storage, and metabolism of NO. The present study was designed to examine the reactions that promote the decomposition, formation, and distribution of extracellular nitrosothiols in the circulation. The disappearance of these species in plasma and whole blood was examined using a high-performance liquid chromatography method to separate low- and high-molecular weight nitrosothiols. We found that incubation of S-nitrosocysteine (CySNO) or S-nitrosoglutathione (GSNO) with human plasma resulted in a rapid decomposition of these nitrosothiols such that <10% of the initial concentration was recovered after 10-15 min. Neither metal chelators (DTPA, neocuproine), nor zinc chloride (glutathione peroxidase inhibitor), acivicin (gamma-glutamyl transpeptidase inhibitor), or allopurinol (xanthine oxidase inhibitor) inhibited the decomposition of GSNO. With both CySNO and GSNO virtually all NO was recovered as S-nitrosoalbumin (AlbSNO), suggesting the involvement of a direct transnitrosation reaction. Electrophilic attack of the albumin-associated thiols by reactive nitrogen oxides formed from the interaction of NO with O(2) was ruled out because one would have expected 50% yield of AlbSNO. Similar results were obtained in whole blood. The amount of S-nitrosohemoglobin recovered in the presence of 10 microM GSNO or CySNO was less than 100 nM taking into consideration the detection limit of the assay used. Our results suggest that serum albumin may act as a sink for low-molecular-weight nitrosothiols and as a modulator of NO(+) transfer between the vascular wall and intraerythrocytic hemoglobin.
...
PMID:Dynamic state of S-nitrosothiols in human plasma and whole blood. 1069 53

Antioxidant components in Aloe vera were examined for lipid peroxidation using rat liver microsomal and mitochondrial enzymes. Among the aloesin derivatives examined, isorabaichromone showed a potent antioxidative activity. The DPPH radical and superoxide anion scavenging activities were determined. As one of the most potent components, isorabaichromone together with feruloylaloesin and p-coumaroylaloesin showed potent DPPH radical and superoxide anion scavenging activities. Electron spin resonance (ESR) using the spin trapping method suggested that the potent superoxide anion scavenging activity of isorabaichromone may have been due to its caffeoyl group. As A. vera has long been used to promote wound healing, the inhibitory effects of aloesin derivatives for cyclooxygenase (Cox)-2 and thromboxane (Tx) A 2 synthase were examined and the participation of p-coumaroyl and feruloyl ester groups in the aloesin skeleton was demonstrated. These findings may explain, at least in part, the wound healing effects of A.vera. Abbreviations. ADP:adenosine diphosphate ASA:ascorbic acid BHT:butylated hydroxytoluene BSA:bovine serum albumin DMPO:5,5-dimethyl-1-pyrroline N-oxide DPPH:1,1-diphenyl-2-picrylhydrazyl EDTA:edetic acid HEPES: N-(2-hydroxyethyl)-piperazine- N-2'-ethane-sulfonic acid NADH:reduced nicotinamide adenine dinucleotide NADPH:reduced nicotinamide adenine dinucleotide phosphate NBT:nitroblue tetrazolium Pg:prostaglandin SOD:superoxide dismutase TBA:thiobarbituric acid TCA:trichloroacetic acid XOD:xanthine oxidase
...
PMID:Antioxidant, free radical scavenging and anti-inflammatory effects of aloesin derivatives in Aloe vera. 1245 82

In this study, we measured the antiallergic activities of ginsenosides isolated from the root of Panax ginseng ( Araliaceae), and of their metabolites, as produced by human intestinal bacteria. Compound K, which was identified as a main metabolite, had the most potent inhibitory activity on beta-hexosaminidase release from RBL-2H3 cells and on the PCA reaction. The inhibitory activity of compound K was more potent than that of disodium cromoglycate, one of the commercial anti-allergic drugs. This compound demonstrated a membrane stabilizing action on differential scanning calorimetry. However, compound K did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that the antiallergic action of compound K originates from its cell membrane stabilizing activity and that the ginsenosides of ginseng are prodrugs with extensive antiallergic properties. Abbreviations. compound K:20- O-beta- D-glucopyranosyl-20( S)-protopanaxadiol DNP:dinitrophenol DSCG:disodium cromoglycate DPPC:dipalmitoylphosphatidylcholine DPPH:1,1-diphenyl-2-picrylhydrazyl HSA:human serum albumin IC 50 :50% inhibitory concentration EC 50 :50% effective concentration XOD:xanthine oxidase ICR:Institute of Cancer Research PBS:phosphate buffered saline PCA:passive cutaneous anaphylaxis RAW264.7:mouse monocyte leukemiaRBL-2H3: rat basophil leukemia SD:Sprague-Dawley
...
PMID:Antiallergic activity of ginseng and its ginsenosides. 1286 69

Derivatives of benzazolo[3,2-a]quinolium salts (QSDs) are reductively activated by the enzymatic reducing agents hypoxanthine (or xanthine)/xanthine oxidase and NADH dehydrogenase as evidenced by the increase in rates of ferricytochrome c (Cyt(III)c) reduction and oxygen consumption, respectively. No correlation between Michaelis-Menten parameters and QSDs redox potentials was found regarding anaerobic or aerobic Cyt(III)c reduction, although maximum rates were observed for nitro-containing QSDs. However, oxygen consumption rates correlate with QSDs redox potentials when NADH dehydrogenase is used as reducing agent. QSDs bind covalently to bovine serum albumin (BSA) under anaerobic conditions, in the presence, and less in the absence, of HX/XO and only if the nitro group is present at the QSD. QSDs react with glutathione (GSH) in the presence of HX/XO but not in its absence, under anaerobic conditions. The amount of reacted GSH increases, and the relative amount of GSSG formed decreases, with an increase in the QSD reduction potential, thus indicating that GSH reacts with reduced nitro-containing QSDs mainly in a manner which does not involve the production of GSSG, presumably, through the formation of the nitroso-QSD-GSH conjugate. QSDs are, thus, novel nitro-containing heterocyclic compounds which could be bioreductively activated to react with oxygen and thiols.
...
PMID:Reductive activation and thiol reactivity of benzazolo[3,2-a]quinolinium salts. 1514 83


<< Previous 1 2 3 4 5 6 7 Next >>

---