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)

A quantitative assay for erythrocyte superoxide dismutase activity using the xanthine-xanthine oxidase-nitro blue tetrazolium system which is applicable to clinical material is described. The in-batch precision of the method is 3.5% and the between-batch precision is 8.8%. Employing this assay, erthrocyte superoxide dismutase activities were measured in 50 normal subjects and in 50 patients with rheumatoid arthritis. There was no significant correlatiion between superoxide dismutase activity and erthrocyte copper concentration. Erythrocyte copper was lower in female rheumatoid patients than in normals. This difference was not accompanied by a difference in superoxide dismutase activity.
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PMID:The relationship between erythrocyte superoxide dismutase activity and erythrocyte copper levels in normal subjects and in patients with rheumatoid arthritis. 94 92

Oxygen-derived free radicals (ODFR) depolymerized synovial-fluid (SF) hyaluronic acid (HA) when hypoxanthine/xanthine oxidase (HX/XAO) was used as the radical generator. The molecular-weight distribution of ODFR-induced SF HA degradation products was determined using high performance liquid chromatography (HPLC) with TSK 5000 PW or TSK 6000 PW size-exclusion columns and simultaneously using 125I-labelled hyaluronate-binding protein (125I-HABP) assay. The exposure of SF HA to hydroxyl-radical flux resulted in the formation of a degradation product having a molecular weight of 13.5 X 10(3) daltons, from which no further degradation was achieved. If the iron chelator desferrioxamine and hydroxyl-radical scavenger mannitol were present in the reaction mixture, the HA peak decreased by 30-50%, as a result of reaction with superoxide radical and hydrogen peroxide. These results show that superoxide radical and hydroxyl radical may have different modes of action on SF HA. The molecular-weight distribution of serum HA from patients with rheumatoid arthritis varied in different individuals and ranged between 275 X 10(3) and 650 X 10(3).
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PMID:Reactive oxygen species and hyaluronate in serum and synovial fluid in arthritis. 221 Sep 71

Inflammation increases plasma levels of ceruloplasmin, a copper protein with possible antioxidant function. This paper describes modulation of these increases by copper intake, and describes combined effects of inflammation and copper intake on Cu-Zn and extracellular (EC) superoxide dismutase (SOD) activities. Turpentine injections in rats fed 1 of 4 copper levels increased ceruloplasmin activities, but values were sensitively limited by copper intake. Cu-Zn SOD activities in the liver, but not in erythrocytes or lungs, were reduced by inflammation in each dietary copper group. Inflammation in rats fed a standard mixed feed diet reduced plasma EC superoxide dismutase activities measured by inhibition of pyrogallol autoxidation. Different results were obtained with 3 xanthine oxidase based SOD assays which were each subject to assay interference. Studies in humans found a group of rheumatoid arthritis patients to possess relatively low erythrocyte SOD and relatively high ceruloplasmin activities. Activity levels of SOD, but not of ceruloplasmin, increased after 4 weeks of copper supplementation (2 mg/day). The fate of cellular Cu-Zn SOD activity contents in inflamed tissues is largely uninvestigated. However, interleukin-1, a hormone released at inflammation sites, elevated Cu-Zn SOD activities in cultured fibroblasts.
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PMID:Effects of inflammation on copper antioxidant enzyme levels. 256 Jun 8

Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-proteolytic activation of latent human neutrophil collagenase and its role in matrix destruction in periodontal diseases. 256 61

Degradation of intact cartilaginous tissue (bovine nasal cartilage) by oxygen-derived free radicals (ODFR) generated enzymatically by xanthine oxidase and hypoxanthine was studied. The degree of tissue destruction was determined by measuring the indentation under a defined compression force as well as by the loss of uronic acid- and hydroxyproline-containing matrix components. Cartilage slices altered by prior elastase treatment were more susceptible to oxygen radical attack than were intact tissue specimens. Degradation of cartilage matrix by ODFR was strongly inhibited by superoxide dismutase or catalase. Coincubation of latent collagenase from polymorphonuclear leukocytes with the ODFR-generating system led to activation of collagenolytic activity, resulting in marked degradation of the bovine cartilage slices. In further studies, activated polymorphonuclear leukocyte-collagenase was shown to degrade intact human articular cartilage to a degree of mechanical insufficiency. Thus, our assay system serves as an in vitro model of tissue damage, which may be relevant to pathophysiologic states such as rheumatoid arthritis.
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PMID:Oxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes. 300 65

The effect of D-penicillamine (DP) and thiopronine on the generation of reactive oxygen species (ROS) both by stimulated polymorphonuclear leucocytes (PMNs) and in a cell-free, xanthine-xanthine oxidase system was investigated. Both drugs significantly reduced hydroxyl radical (OH.) generation in the PMN system, however, increasing trends of OH. levels were noticed in a cell-free ROS generating system. Although the opposing effects on ROS levels were verified, these two agents showed a similar behaviour presumably due to their structural similarity. The properties of these agents that affect ROS levels may contribute to their beneficial and toxic actions in inflammatory as well as immunoregulatory processes of rheumatoid arthritis (RA).
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PMID:Decreased hydroxyl radical generation from polymorphonuclear leucocytes in the presence of D-penicillamine and thiopronine. 303 83

To test the scavenging of reactive oxygen species (ROS), we added synovial fluids from patients with rheumatoid arthritis (RA) and osteoarthritis, as well as hyaluronic acid (HA) and its 2 subcomponents, D-glucuronic acid and N-acetyl-D-glucosamine, to 2 ROS-generating systems, activated neutrophils and xanthine-xanthine oxidase. Synovial fluid from RA patients, HA, and D-glucuronic acid markedly decreased the O2-, H2O2, OH., and chemiluminescence measured in both systems. HA and synovial fluid, which are known to be susceptible to degradation by excessive ROS in RA patients, also seem to play an active role in protecting articular tissues from oxidative damage.
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PMID:Antioxidant activity of synovial fluid, hyaluronic acid, and two subcomponents of hyaluronic acid. Synovial fluid scavenging effect is enhanced in rheumatoid arthritis patients. 334 32

Levels of free sulph-hydryl (SH) groups are depressed in the sera of patients with rheumatoid arthritis, especially during active disease. However, the mechanism underlying this effect is not known. We have investigated several oxidative species generated during the inflammatory process for their ability to react with serum SH in vitro. Our results show that serum oxidase enzymes (e.g. caeruloplasmin) do not have this activity but that "active oxygen species" generated either by an enzymatic reaction (xanthine plus xanthine oxidase) or by neutrophils stimulated with heat-aggregated IgG cause rapid oxidation of serum SH groups. The use of selective inhibitors of active oxygen species has demonstrated that this reaction is mediated by hydrogen peroxide. This compound is secreted in considerable amounts by activated phagocytic cells, especially neutrophils. Thus, serum SH levels may reflect phagocytic activity in patients with rheumatoid arthritis. We suggest that serum SH groups act as important extracellular scavengers of peroxides and so help to protect cells from damage by these molecules.
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PMID:The oxidation of serum sulph-hydryl groups by hydrogen peroxide secreted by stimulated phagocytic cells in rheumatoid arthritis. 671 52

The effect of reactive oxygen species (ROS) generated by a xanthine oxidase hypoxanthine system (mainly H2O2) on proteoglycan (PG) metabolism and structure was investigated in vitro, using cell monolayers of cultured rabbit articular chondrocytes and purified resident and newly synthesized proteoglycans. It was shown that ROS generated in this system frequently stimulate (at low concentrations), and consistently inhibit (at higher concentrations), the incorporation of 35SO4 and 3H-glucosamine into PG molecules synthesized by cultured chondrocytes. The inhibition of isotopes' incorporation at higher enzyme concentrations was suppressed completely by heating xanthine oxidase and allopurinol with superoxide dismutase (SOD) and catalase. ROS at high concentration also inhibited 3H-uridine incorporation but had no effect on 35SO4 and 3H-uridine uptake by the cells. They also alter hyaluronan (HA) and PG monomers by fragmenting the core protein moiety and destroying the hyaluronic acid binding region. Altered PG monomers do not interact with HA to form complexes, but fragmented HA still retain a significant PG monomer-binding capacity. PG-HA complexes are easily and irreversibly destroyed by ROS. These results suggest that ROS may at low fluxes stimulate PG-synthesis under physiological conditions and alter cartilage metabolism and structure in conditions where they are overproduced, such as in rheumatoid arthritis, and in hemochromatosis and other iron storage diseases.
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PMID:Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans. 800 11

Sera of patients with various inflammatory and autoimmune rheumatic diseases were screened for the presence of xanthine oxidase (XOD) and compared to sera from healthy donors and patients with nonrheumatic diseases including AIDS, internal diseases, and different carcinomas. Up to 50-fold higher levels of XOD were detected in rheumatic sera (P < 0.001). In addition, serum sulfhydryls (SH) were determined as sensitive markers of oxidative stress. The SH status in rheumatic patients was diminished by 45-75% (P < 0.001) and inversely correlated to the concentration of serum XOD (R = 0.73), suggesting a causal interrelation. The depletion of serum sulfhydryls by the oxyradical-producing XOD/acetaldehyde system was mimicked successfully ex vivo in human serum from healthy donors. Cortisone treatment of patients suffering from systemic lupus erythematosus and rheumatoid arthritis impressively normalized elevated XOD concentrations in rheumatic sera to those of healthy controls. The participation of xanthine oxidase in the depletion of serum antioxidants in rheumatic patients is discussed in the light of substrate availability and Km values.
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PMID:Elevated levels of xanthine oxidase in serum of patients with inflammatory and autoimmune rheumatic diseases. 822 62


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