Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using paraquat, adriamycin, and anthraquinone 6-sulfonate, we have investigated the ability of radical-driven Fenton reactions to oxidize formate or deoxyribose when catalyzed by iron complexed with citrate, ADP, ATP, or pyrophosphate. Radicals were generated either radiolytically or enzymatically with xanthine oxidase or ferredoxin reductase. With each radical source, the citrate, ADP, and ATP complexes were at least 50% as active as Fe(EDTA) at catalyzing deoxyribose oxidation, and slightly less active as catalysts of CO2 formation from formate. Fe(pyrophosphate) was less efficient and in some cases inactive. Although it is not possible to definitively identify the oxidant involved, it behaved more like the hydroxyl radical than the proposed ferryl or peroxoferrous species formed in equivalent reactions catalyzed by nonchelated iron, which can oxidize deoxyribose but not formate. Chelator concentrations of 1-2 mM were required for maximum effect, which implies that the major effect of the chelators is on the reactivity of Fe2+ in the Fenton reaction with H2O2. This also suggests that any iron available physiologically could participate in the Fenton reaction in a nonchelated form, and produce a ferryl species rather than the hydroxyl radical. Reactions of the organic radicals contrast with the equivalent reactions of superoxide (Haber-Weiss reaction) for which the same iron chelates are all very inefficient catalysts. Fenton reactions driven by organic reducing radicals may therefore contribute more to the toxicity of redox cycling compounds than equivalent reactions of superoxide.
 ...
PMID:Radical-driven Fenton reactions: studies with paraquat, adriamycin, and anthraquinone 6-sulfonate and citrate, ATP, ADP, and pyrophosphate iron chelates. 282 82

Our recent studies have indicated that release of ATP/ADP from platelets causes enhanced O2-. responses in stimulated neutrophils. The current investigations were designed to provide further details of this phenomenon, to determine the structure-function correlates of the adenine compounds, and to assess if the results might be explained by the formation of a single metabolic product of ATP. ATP, ADP, AMP and adenosine enhanced O2-. responses of rat neutrophils stimulated with immune complexes or formyl chemotactic peptide (FMLP) but had no effect on responses of phorbol ester-stimulated neutrophils. Similar results were obtained in human neutrophils stimulated with immune complexes; when FMLP was the agonist, the results were divergent: ATP and ADP enhanced the responses, whereas AMP and adenosine were inhibitory. In structure-function studies, hydrolytically resistant forms of ATP (and other adenine nucleotides) containing blocked or cross-linked phosphate groups were active, suggesting that hydrolysis of these compounds to a common metabolic product is not required for their effects on O2-. responses. In contrast, other chemical modifications of the ribose ring or adenine base of ATP resulted in greatly diminished activity. To further pursue the question of whether metabolism of the adenine compounds via the adenosine pathway was related to the observed effects on O2-. responses, addition to rat neutrophils of inhibitors of adenosine deaminase, S-adenosyl homocysteine hydrolase, or xanthine oxidase failed to reproduce or augment the enhancement effects of the adenine compounds on O2-. responses, suggesting that metabolism of the adenine compounds to a common product may not be a requirement for the observed effects. Although the manner by which the adenine compounds affect O2-. responses is not known, the data suggest that adenosine and adenine nucleotides have important regulatory effects on oxygen radical responses of stimulated neutrophils.
 ...
PMID:Regulatory effects of adenosine and adenine nucleotides on oxygen radical responses of neutrophils. 283 59

The protective effects of various tannins on ocular lens against the induced oxidative damage were examined. Oxidative damage on mouse lenses was induced by incubating them with xanthine-xanthine oxidase, ADP and Fe3+ (X.XOD system). X.XOD system caused an increase in lipid peroxide of lens membrane and decreases in Na,K-ATPase and GSH reductase activities in the lenses. After pretreatment of lenses with X.XOD system, the lenses were incubated with tannins in the medium containing no X.XOD system and the effects of tannins on biochemical parameters in the lenses were determined. Higher molecular tannins (penta-O-galloyl-beta-D-glucopyranose and geraniin) decreased the lipid peroxide in the lens and restored GSH content, Na,K-ATPase and GSH reductase activities in the lens to the level comparable to control. However, all of tannins tested restored much insufficiently the cation level (ratio of Na+/K+) in the lens regardless of extents of restoration of Na,K-ATPase level by them. Because it was supposed that tannins might act primarily on the plasma membrane, the effect of tannins on lens plasma membrane was examined using cell free system. Lens was homogenated and separated into membrane pellet and supernatant. When the pellet was treated with X.XOD system, the lipid peroxide in the pellet increased and its Na,K-ATPase activity decreased. In addition, the treated pellet decreased the GSH level and GSH reductase activity in the supernatant, when the pellet was combined with the supernatant. Higher molecular tannins reduced lipid peroxide content in the X.XOD-treated pellet to control level and the pellet in which lipid peroxide content was reduced by tannins caused much less decreases of GSH level and GSH reductase activity in the supernatant. These results suggest that, in intact lens, higher molecular tannins act on plasma membrane to eliminate lipid peroxide produced by the X.XOD system and consequently suppress the decreases in both Na,K-ATPase and GSH reductase activities without their entering inside the cell.
 ...
PMID:Effects of tannins on the oxidative damage of mouse ocular lens. I. Using the oxidative damage model induced by the xanthine-xanthine oxidase system. 284 23

Human polymorphonuclear leucocytes were found to promote peroxidation linolenic acid micelles. The peroxidation was markedly enhanced by addition of ferric iron, either in the form of chloride, ADP-complex or EDTA to the phosphate-buffered reaction mixture. The leucocyte oxygen burst was induced by the addition of the lipid micelles, and no other stimulatory agent was therefore required. Pretreatment of the leucocytes with cytochalasin B did not inhibit t.e lipid peroxidation which indicates that phagocytosis was not part of the peroxidative mechanism. Lipid peroxidation was inhibited by alpha-tocopherol acetate, butylated hydroxytoluene, manganese ions and desferrioxamine but not by superoxide dismutase, catalase or the hydroxyl radical scavenger dimethylsulfoxide. Lipid peroxidation promoted by xanthine oxidase, was studied for comparison. This was inhibited by superoxide dismutase, indicating that xanthine oxidase, in contrast to leucocytes, promotes lipid peroxidation via a superoxide-dependent mechanism. Manganese ions and butylated hydroxytoluene, and to a lesser extent alpha-tocopherol, were also inhibitors. The leucocyte promoted lipid peroxidation is similar to the well-known peroxidation promoted by microsomal NADPH-cytochrome P450 reductase, which also is not induced by superoxide radicals. Peroxidation of lipids may be a mechanism whereby granulocytes express tissue damage in for example inflammation and ischaemia.
 ...
PMID:Peroxidation of linolenic acid promoted by human polymorphonuclear leucocytes. 287 64

Ferritin was found to promote the peroxidation of phospholipid liposomes, as evidenced by malondialdehyde formation, when incubated with xanthine oxidase, xanthine, and ADP. Activity was inhibited by superoxide dismutase but markedly stimulated by the addition of catalase. Xanthine oxidase-dependent iron release from ferritin, measured spectrophotometrically using the ferrous iron chelator 2,2'-dipyridyl, was also inhibited by superoxide dismutase, suggesting that superoxide can mediate the reductive release of iron from ferritin. Potassium superoxide in crown ether also promoted superoxide dismutase-inhibitable release of iron from ferritin. Catalase had little effect on the rate of iron release from ferritin; thus hydrogen peroxide appears to inhibit lipid peroxidation by preventing the formation of an initiating species rather than by inhibiting iron release from ferritin. EPR spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide was used to observe free radical production in this system. Addition of ferritin to the xanthine oxidase system resulted in loss of the superoxide spin trap adduct suggesting an interaction between superoxide and ferritin. The resultant spectrum was that of a hydroxyl radical spin trap adduct which was abolished by the addition of catalase. These data suggest that ferritin may function in vivo as a source of iron for promotion of superoxide-dependent lipid peroxidation. Stimulation of lipid peroxidation but inhibition of hydroxyl radical formation by catalase suggests that, in this system, initiation is not via an iron-catalyzed Haber-Weiss reaction.
 ...
PMID:Ferritin and superoxide-dependent lipid peroxidation. 298 54

The enzymatic inosine 5'-monophosphate assay described by Grassl [in, Methods of Enzymatic Analysis (H. U. Bergman, ed.), pp. 2168-2171, Academic Press, New York (1974)] is highly nonspecific, as ITP, ATP, ADP, AMP, and adenosine react stoichiometrically. The reactivity with the adenine derivatives is due to the tri- and diphosphatase activity of alkaline phosphatase (AP), coupled with adenosine deaminase (and possibly AMP deaminase) contamination of commercially available preparations of AP, purine-nucleoside phosphorylase, and/or xanthine oxidase. The inclusion of coformycin (0.05 microgram/ml), a potent inhibitor of these deaminases, completely eliminated the cross-reactivity. ITP, however, still reacted stoichiometrically due to the tri- and diphosphatase activity of AP. Meyer and Terjung [Amer. J. Physiol. 237 C111-C118 (1979)] introduced a modification of Grassl's procedure, substituting 5'-nucleotidase for AP. It has been found that this disallows reactivity with ATP, ADP, and ITP but that AMP and adenosine still react completely. Coformycin prevents this cross-reactivity. It is therefore recommended that the assay be carried out with 5'-nucleotidase (instead of AP) and coformycin, in order to achieve a more specific assay, and one more suitable for use with whole tissue extracts.
 ...
PMID:An enzymatic inosine 5'-monophosphate assay of increased specificity. 298 81

Lipid peroxidation of microsomal membranes isolated from rat liver, and Morris hepatomas 9618A (slow-growing) and 3924A (fast-growing) was induced by superoxide radicals generated by the action of xanthine oxidase on xanthine. The peroxidation, measured as malondialdehyde and lipid hydroperoxide formation, was optimized with regard to iron concentration and chelation of iron by ADP. In such conditions hepatoma microsomes catalyze lower rates of lipid peroxidation than the normal counterpart. However, while microsomes from hepatoma 3924A show a marked decrease in both the malondialdehyde and hydroperoxide production rates, microsomes from hepatoma 9618A differ moderately from the control, mainly in the long-term production of hydroperoxides. It is also reported here that the 9618A microsomes partially lack cytochrome P-450 (about 40% deficiency), but they have a fatty acid composition similar to that of control. No differences were found in the content of vitamin E between normal and hepatoma 3924A microsomes. Moreover, induction of vitamin E deficiency in hepatoma 3924A microsomes does not influence the rate of either malondialdehyde or lipid hydroperoxide production. On the basis of these results and previous data on the lipid composition of hepatoma 3924A microsomes it is proposed that the high resistance to superoxide-dependent lipid peroxidation of hepatoma 3924A microsomes is related to the low substrate availability rather than the content of membrane antioxidants; and a limitation only in the propagation phase characterizes the hepatoma 9618A microsomal lipid peroxidation and would be due to the partial deficiency of the endogenous propagating agent, cytochrome P-450.
 ...
PMID:Superoxide-dependent lipid peroxidation and vitamin E content of microsomes from hepatomas with different growth rates. 298 56

Preincubation of rat brain synaptosomes with xanthine and xanthine oxidase (X/XO) in Ca2+-free Krebs buffer resulted in a 27% inhibition of synaptosomal gamma-aminobutyric acid (GABA) uptake. Addition of 1.5 mM CaCl2 increased the inhibition with X/XO to 46%, and inhibition was essentially complete when the calcium ionophore A23187 also was included. In other studies, preincubation of purified rat brain mitochondria with the combination of X/XO and 4 microM CaCl2 produced a significant (38%) decrease in state 3 respiration with glutamate/malate as substrate that was not seen with either X/XO or Ca2+ alone. Similar results were obtained using cultured mouse spinal cord neurons in which incubation with X/XO/ADP/FeCl2 and A23187 produced membrane damage as assessed by a 32% reduction of neuronal Na+, K+-ATPase activity. Neither X/XO/ADP/FeCl2 nor A23187 alone caused detectable inhibition. These results demonstrate the synergistic damaging effect of free radicals and Ca2+ on membrane function. In addition, they suggest that free radical-induced peroxidation of membrane lipid, occurring focally during complete or nearly complete ischemia in vivo, could result in intense cellular perturbation when coupled with increased intracellular Ca2+.
 ...
PMID:Calcium enhances in vitro free radical-induced damage to brain synaptosomes, mitochondria, and cultured spinal cord neurons. 299 23

O2- was produced by gamma irradiation of formate solutions, by the action of xanthine oxidase on hypoxanthine and O2, and by the action of ferredoxin reductase on NADPH and paraquat in the presence of O2. Its reaction with H2O2 and various iron chelates was studied. Oxidation of deoxyribose to thiobarbituric acid-reactive products that was appropriately inhibited by OH. scavengers, or formate oxidation to CO2, was used to detect OH(.). With each source of O2-, and by these criteria, Fe(EDTA) efficiently catalyzed this (Haber-Weiss) reaction, but little catalysis was detectable with iron bound to DTPA, citrate, ADP, ATP, or pyrophosphate, or without chelator in phosphate buffer. O2- produced from xanthine oxidase, but not from the other sources, underwent another iron-dependent reaction with H2O2, to produce an oxidant that did not behave as free OH(.). It was formed in phosphate or bicarbonate buffer, and caused deoxyribose oxidation that was readily inhibited by mannitol or Tris, but not by benzoate, formate, or dimethyl sulfoxide. It did not oxidize formate to CO2. Addition of EDTA changed the pattern of inhibition to that expected for a reaction of OH(.). The other chelators all inhibited deoxyribose oxidation, provided their concentrations were high enough. The results are compatible with iron bound to xanthine oxidase catalyzing production of a strong oxidant (which is not free OH.) from H2O2 and O2- produced by the enzyme.
 ...
PMID:Iron and xanthine oxidase catalyze formation of an oxidant species distinguishable from OH.: comparison with the Haber-Weiss reaction. 300 38

Human polymorphonuclear leucocytes were found to promote peroxidation of phospholipid liposomes upon stimulation by phorbol myristate acetate. Peroxidation required the presence of either pyrophosphate-chelated or ADP-chelated iron, whereas iron chelated to EDTA or ATP had no effect. Peroxidation was also catalyzed by ferritin, but not by transferrin. Superoxide dismutase abolished the peroxidation, whereas catalase and apparently also the hydroxyl radical scavenger dimethyl sulphoxide were inactive, indicating that the peroxidation was mediated by superoxide radicals but not by hydrogen peroxide or hydroxyl radicals. Xanthine oxidase-promoted peroxidation was studied for comparison and showed similar characteristics except that transferrin catalyzed the peroxidation. Peroxidation of membrane lipids may be a mechanism whereby granulocytes cause tissue damage in inflammation. The drugs paracetamol, gentisic acid and 5-aminosalicylic acid inhibited lipid peroxidation, probably through their ability to react with the superoxide anion.
 ...
PMID:Peroxidation of liposomes promoted by human polymorphonuclear leucocytes. 301 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>