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)

Free radical derived from xanthine oxidase damage to rabbit articular chondrocytes cultured in serum-free medium and antioxidant defense factors protecting chondrocytes from free radical were studied. The results showed that free radical mediated an inhibition of DNA as well as proteoglycan synthesis in cultured chondrocytes and selenium, a-tocopherol and L-ascorbic acid failed to protect chondrocytes from free radicals.
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PMID:[Free radical damage to chondrocytes and protection by selenium, tocopherol and ascorbic acid using serum-free medium method]. 147 94

By using monolayer culture technique, the effect of endogenous free radicals on rabbit articular chondrocytes was studied. The free radicals were provided through the action of xanthine oxidase (XO) on xanthine (X). The amount of DNA in chondrocytes was measured with ethidium bromide method for direct fluorometric estimation of DNA. The synthesis of proteoglycan (PG) was assayed through 35S-Na2SO4 incorporation followed by inverted microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results indicated that chondrocytes could be damaged by endogenous free radicals generated by the action of XO on X, and these free radicals may be related to the pathogenesis of cartilage aging, degeneration, degenerative joint disease and arthritis.
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PMID:[The effect of free radicals on the rabbit articular chondrocytes in monolayer culture]. 191 13

The susceptibility of rat mast-cell heparin to oxidative degradation was examined. Heparin as a component of intact mast-cell granules (MCG) was degraded following ingestion by normal human neutrophils. In contrast, neutrophils from patients with chronic granulomatous disease (CGD), which do not respond to stimulation with respiratory-burst activity, exhibited a greatly diminished ability to degrade phagocytosed MCG heparin. MCG-associated heparin also was cleaved by H2O2 plus Fe2+ (Fenton's reagent). Isolated heparin proteoglycan (average Mr approx. 750,000) was rapidly cleaved to smaller molecules similar in size to commercial pig heparin upon exposure to Fenton's reagent. This cleavage was inhibited by catalase and by the hydroxyl-radical (OH.)-scavenger mannitol, but not by superoxide dismutase (SOD). The cleavage products retained approx. 26% of the anticoagulant activity of the native molecule. The heparin proteoglycan was also cleaved by acetaldehyde/xanthine oxidase/FeSO4, a system that generates superoxide (O2.-), H2O2 and OH.. Whereas the cleavage at relatively high iron ion concentrations was inhibited by catalase and mannitol but not by SOD, at lower iron ion concentrations the cleavage was inhibited by catalase, mannitol and SOD. These findings suggest the involvement of OH., which at high Fe2+ concentrations is generated by Fenton's reagent (H2O2 plus Fe2+), and at low iron ion concentrations is generated by the iron-ion-catalysed interaction between O2.- and H2O2 (Haber-Weiss reaction). These studies suggest that oxygen radicals generated by activated phagocytes may contribute to the degradation in vivo of both solubilized and granule-associated proteoglycan heparin.
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PMID:Oxidative degradation of rat mast-cell heparin proteoglycan. 217 84

Oxygen-derived reactive species, generated enzymatically by the action of xanthine oxidase upon hypoxanthine, significantly inhibit proteoglycan synthesis by cultured bovine articular cartilage (Bates, E.J., Lowther, D.A. and Handley, C.J. (1984) Ann. Rheum. Dis. 43, 462-469). Here we extend these investigations and show, through the use of catalase and the specific iron chelator diethylenetriaminepentaacetic acid, that the active species involved is H2O2 and not the hydroxyl radical. Incubations of cartilage with H2O2 at concentrations of 1 X 10(-4) M and above are also inhibitory to proteoglycan synthesis. Subsequent recovery of the tissue is dependent upon the initial dose of xanthine oxidase or H2O2. Xanthine oxidase at 84 mU per incubation results in a prolonged inhibition of proteoglycan synthesis which is still apparent after 14 days in culture. Lower concentrations of xanthine oxidase (21-66 mU) are inhibitory to proteoglycan synthesis, but the tissue is able to synthesise proteoglycans at near normal rates after 3 days in culture. The inhibition of proteoglycan synthesis by 1 X 10(-4) M H2O2 is completely reversed after 5 days in culture, whereas 1 X 10(-3) M H2O2 results in a more prolonged inhibition. The synthesis of the proteoglycan core protein is inhibited, but the ability of the newly formed proteoglycans to aggregate with hyaluronic acid is unimpaired.
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PMID:Inhibition of proteoglycan synthesis by hydrogen peroxide in cultured bovine articular cartilage. 383 55

Commercial xanthine oxidase, widely used for generation of oxygen radicals in vitro, is usually contaminated by proteolytic activity, which limits its utility in studies of oxygen radical damage to protease sensitive substrates. An easily prepared fraction of fetal calf serum was found to inhibit virtually all of the proteolytic contaminant without affecting superoxide generation. The effects attainable with the "purified" enzyme were demonstrated with two protease sensitive targets: proteoglycan subunit from cartilage and fibronectin from human plasma.
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PMID:Inhibition of the proteolytic contaminant in commercial xanthine oxidase preparations by serum protein fractions. 391 52

Superoxide radical, generated enzymatically by the action of xanthine oxidase on hypoxanthine, significantly inhibited proteoglycan synthesis by cultured bovine articular cartilage. This inhibition was not due to the generation of uric acid or to the generation of superoxide per se. It was immediate in onset and still evident after six days in culture. The inhibition was similar for both 35S-sulphate and 3H-acetate incorporation into glycosaminoglycans and could not be reversed by addition of beta-D-benzyl xyloside. Protein synthesis was also inhibited.
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PMID:Oxygen free-radicals mediate an inhibition of proteoglycan synthesis in cultured articular cartilage. 633 28

Proteoglycan-hyaluronate aggregates were incubated with oxygen-derived reactive species generated enzymatically by the action of xanthine oxidase upon hypoxanthine. Analysis of the products of the incubation by caesium sulphate zonal sedimentation revealed that degradation of aggregate had occurred. This effect was reversed by inclusion of superoxide dismutase, catalase or diethylenetriaminepentaacetic acid in the incubations suggesting that hydroxyl radicals were the active species. Separate analysis by gel filtration chromatography on Sepharose CL-2B of proteoglycan monomer subjected to a similar treatment indicated that the molecule is minimally degraded. These results are discussed with reference to the well established degradation of hyaluronate by oxygen-derived reactive species.
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PMID:Effect of oxygen-derived reactive species on cartilage proteoglycan-hyaluronate aggregates. 654 42

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

To research the mechanism of cartilage injury in non-purulent arthritis we have used the method of chondrocytes in monolayer culture in vitro and have observed the effect of free radicals generated by the xanthine oxidase and xanthine on DNA, matrix proteoglycan (PG) and collagen synthesis of human embryo chondrocytes. Our results showed that oxygen free radicals generated by xanthine oxidase and xanthine inhibited strongly the synthesis of DNA, PG and collagen of human embryo chondrocytes. On the bases of these results we suggest that oxygen free radicals from polymorphonuclear leukocytes and phagocytes would be important factors of cartilage injury in the arthritis.
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PMID:[Oxygen free radicals mediate an inhibition of DNA and matrix proteoglycan, collagen synthesis in cultured human embryo chondrocytes]. 803 26

There is considerable evidence suggesting that reactive oxygen species (ROS) are implicated in the pathogenesis of ischemic, toxic, and immunologically-mediated renal injury. In experimental renal ischemia, ROS sources include the electron transport chain, oxidant enzymes (xanthine oxidase), phagocytes, and auto-oxidation of epinephrine. ROS cause lipid peroxidation of cell and organelle membranes and, hence, disruption of the structural integrity and capacity for cell transport and energy production, especially in the proximal tubule segment. In experimental immune glomerulonephritis, ROS are generated by both infiltrating blood-borne cells (polymorphonuclear leukocytes and monocytes) and resident glomerular cells, mainly mesangial cells. Their formation results in morphologic lesions and in modifications of glomerular permeability to proteins through activation of proteases and reduction of proteoglycan synthesis. Additionally, they promote a reduction in glomerular blood flow and glomerular filtration rate through liberation of vasoconstrictory bioactive lipids (prostaglandins, thromboxane, and platelet activating factor) and, possibly, inactivation of relaxing nitric oxide. Further studies are needed to address the role of ROS in human glomerular diseases.
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PMID:Involvement of reactive oxygen species in kidney damage. 822 Oct 27


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