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:1.11.1.6 (catalase)
55,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strand breaks can be produced in the DNA of intact granulocytes by a flux of oxyradicals (O2- and H2O2) generated by tetradecanoylphorbol acetate (TPA) or by a flux of H2O2 generated by glucose oxidase. The mechanism by which such breaks are induced is still uncertain. Lipophilic chelators such as dipyridyl and 1,10-phenanthroline (OP) strongly inhibit strand breaks induced by H2O2, presumably because of their ability to chelate intracellular iron. We now report that dipyridyl also partially inhibits strand breaks in TPA-stimulated granulocytes while a "copper-specific" lipophilic chelator, neocuproine, has no effect. As opposed to these effects, OP increases the number of strand breaks in TPA-stimulated granulocytes. Superoxide dismutase (SOD) (but not catalase) partially blocks this increase. Both the cell-impermeable chelator, EDTA, and neocuproine strongly block the increase also. In fact, in the presence of EDTA, OP behaves like dipyridyl and inhibits strand breaks. Preformed OP2-copper(II) complex causes DNA breaks in TPA-stimulated granulocytes. The paradoxical effect of OP may be explained by assuming that OP may form two different metal complexes, a DNA-damaging complex with copper or an inhibitory complex with iron. If copper(II) and O2- are present, the first complex may form and the net effect may be an increase in strand breaks. If the formation of this complex is prevented by SOD, EDTA, or neocuproine, then OP may complex iron and the net effect may be (like dipyridyl) an inhibition of strand breaks. The source of the copper responsible for the formation of OP2-copper complex is unknown.
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PMID:Effect of lipophilic chelators on oxyradical-induced DNA strand breaks in human granulocytes: paradoxical effect of 1,10-phenanthroline. 131 2

To understand the direct involvement of free radicals causing reduction in endothelium-dependent relaxation of isolated canine coronary ring preparations, this study was undertaken to examine the effect of free radicals generated from dihydroxy fumarate (DHF) plus Fe(3+)-ADP or from H2O2 plus FeSO4. The vasodilators (acetylcholine, bradykinin, A23187, and nitroglycerin) were given after DHF/Fe(3+)-ADP or H2O2/FeSO4 was removed from the organ chamber. The earlier DHF/Fe(3+)-ADP exposure produced an attenuation of the relaxation of the rings induced by acetylcholine, bradykinin, or A23187 but not of the relaxation induced by nitroglycerin. The observed effect of previous DHF/Fe(3+)-ADP exposure was significantly protected in the vessels isolated from the dogs treated with alpha-tocopherol. In the experiments for assessing the effect of various scavengers, 1O2 scavenger histidine or iron chelator deferoxamine effectively protected the attenuation induced by DHF/Fe(3+)-ADP exposure of the relaxation elicited by acetylcholine; superoxide dismutase (SOD), catalase, or dimethyl sulfoxide (DMSO) had no effect on this system. Furthermore, the relaxation elicited by acetylcholine, but not nitroglycerin, was significantly attenuated by the earlier exposure to .OH generated by Fenton's reagent (H2O2+FeSO4); the attenuation was significantly protected by DMSO. These results are consistent with the view that .OH, 1O2, and/or iron-dependent reactive species selectively damage endothelium-dependent relaxation as opposed to endothelium-independent relaxation in endothelium-intact coronary ring preparations. It is also postulated that lipid peroxidation may be responsible for this effect.
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PMID:Oxygen free radical-mediated selective endothelial dysfunction in isolated coronary artery. 131 48

Ethanol is metabolized to acetaldehyde by hepatic microsomes in a reaction that requires cytochrome P-450, and a role for hydroxyl radicals has been implicated in this process. However, previous spin trapping experiments have failed to demonstrate the production of hydroxyl radicals by liver microsomes unless iron or other metal catalysts have been added. The spin trapping experiments described in this report provide unambiguous evidence that liver microsomes form hydroxyl radicals during oxidation of NADPH, that the addition of exogenous iron is unnecessary for this process, and that hydroxyl radicals participate in the metabolism of ethanol. Liver microsomes are known to metabolize ethanol to the 1-hydroxyethyl radical, and our experimental data support the conclusion that a significant part of the production of the 1-hydroxethyl radical occurs as a consequence of hydroxyl radical attack on ethanol. Lack of previous observation of microsomal hydroxyl radical production in spin trapping experiments is shown to be related to the contamination of the microsomes with catalase.
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PMID:Hydroxyl radicals are generated by hepatic microsomes during NADPH oxidation: relationship to ethanol metabolism. 131 60

Using the electron spin resonance/spin trapping system, 4-pyridyl 1-oxide N-tert-butylnitrone (4-POBN)/ethanol, hydroxyl radical was detected as the alpha-hydroxyethyl spin trapped adduct of 4-POBN, 4-POBN-CH(CH3)OH, from phorbol 12-myristate 13-acetate-stimulated human neutrophils and monocytes without the addition of supplemental iron. 4-POBN-CH(CH3)OH was stable in the presence of a neutrophil-derived superoxide flux. Hydroxyl radical formation was inhibited by treatment with superoxide dismutase, catalase, and azide. Treatment with a series of transition metal chelators did not appreciably alter 4-POBN-CH(CH3)OH, which suggested that hydroxyl radical generation was mediated by a mechanism independent of the transition metal-catalyzed Haber-Weiss reaction. Kinetic differences between transition metal-dependent and -independent mechanisms of hydroxyl radical generation by stimulated neutrophils were demonstrated by a greater rate of 4-POBN-CH(CH3)-OH accumulation in the presence of supplemental iron. Detection of hydroxyl radical from stimulated monocyte-derived macrophages, which lack myeloperoxidase, required the addition of supplemental iron. The addition of purified myeloperoxidase to an enzymatic superoxide generating system resulted in the detection of hydroxyl radical that was dependent upon the presence of chloride and was inhibited by superoxide dismutase, catalase, and azide. These findings implicated the reaction of hypochlorous acid and superoxide to produce hydroxyl radical. 4-POBN-CH(CH3)OH was not observed upon stimulation of myeloperoxidase-deficient neutrophils, whereas addition of myeloperoxidase to the reaction mixture resulted in the detection of hydroxyl radical. These results support the ability of human neutrophils and monocytes to generate hydroxyl radical through a myeloperoxidase-dependent mechanism.
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PMID:Spin trapping evidence for myeloperoxidase-dependent hydroxyl radical formation by human neutrophils and monocytes. 131 21

To examine the effects of activated neutrophils (PMNs) on Na(+)-K(+)-ATPase, phorbol 12-myristate 13-acetate (PMA)-stimulated PMNs were incubated with canine renal cortical basolateral membrane (BLM), and BLM ouabain-sensitive Na(+)-K(+)-ATPase activity was subsequently quantified. Na(+)-K(+)-ATPase activity decreased to 40.0 +/- 8.7% (SE) of control in the presence of activated PMNs, from 0.89 +/- 0.12 to 0.34 +/- 0.05 mumol Pi.mg protein-1.min-1. This inhibition coincided with a decrease in the apparent Michaelis constant (Km) for ATP from 0.18 +/- 0.02 to 0.05 +/- 0.01 mM. Inclusion of catalase (CAT) and superoxide dismutase (SOD) in the BLM/PMN/PMA incubation mixture resulted in partial preservation of enzyme activity, with an increase to 57.0 +/- 4.6% of control with CAT alone and to 70.0 +/- 5.3% with both CAT and SOD. SOD alone had no protective effect. Neither the myeloperoxidase inhibitor azide nor the hypochlorous acid scavenger L-methionine preserved enzyme activity. Hydroxyl radical scavengers and iron chelators were also ineffective in attenuating Na(+)-K(+)-ATPase inhibition by activated PMNs. These results indicate that activated PMNs mediate a decrease in BLM Na(+)-K(+)-ATPase activity characterized by a reduction in maximum velocity and Km for ATP that appears to be mediated in part by reactive oxygen metabolites.
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PMID:Activated neutrophils inhibit Na(+)-K(+)-ATPase in canine renal basolateral membrane. 131 73

The effect of age on the toxicity of diquat, a redox cycling compound, was investigated in hepatocytes isolated from mature (6 months) and old (24-29 months) male Fischer 344 rats. Hepatocytes of old rats were more sensitive than those of mature rats to diquat-induced cytotoxicity (lactate dehydrogenase release into the medium). Cell death was preceded by glutathione disappearance, and rates of glutathione depletion were similar in mature and old hepatocytes. In contrast, diquat-induced formation of thiobarbituric acid-reactive substances was much greater in the hepatocytes from old rats, suggesting that increased lipid peroxidation caused the enhanced cytotoxicity. Further experiments revealed that: 1) hepatocytes of mature and old rats were equally sensitive to iron-induced lipid peroxidation; 2) diquat-stimulated production of superoxide anion radical in liver microsomes did not increase with age, but decreased 43%; 3) superoxide dismutase activity was similar in hepatocytes of mature and old rats; 4) inhibition of catalase activity (which diminishes with age in male rats) did not increase diquat toxicity; and 5) malondialdehyde disappearance in intact hepatocytes decreased (33%) with age, but the toxicological significance of the decline in metabolism was uncertain. Thus, the results demonstrated that diquat-induced lipid peroxidation and cytotoxicity increase with age in male rat hepatocytes, but the enhanced sensitivity to diquat poisoning remains unexplained.
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PMID:Age-associated enhancement of diquat-induced lipid peroxidation and cytotoxicity in isolated rat hepatocytes. 132 Jun 87

The use of dichlorofluorescin (DCFH) as a measure of reactive oxygen species was studied in aqueous media. Hydrogen peroxide oxidized DCFH to fluorescent dichlorofluorescein (DCF), and the oxidation was amplified by the addition of ferrous iron. Hydrogen peroxide-induced DCF formation in the presence of ferrous iron was completely inhibited by deferoxamine and partially inhibited by ethylenediaminetetraacetic acid, but was augmented by diethylenetriaminepentaacetic acid. Iron-peroxide-induced oxidation of DCFH was partially inhibited by catalase but not by horseradish peroxidase. Nonchelated iron-peroxide oxidation of DCFH was partially inhibited by several hydroxyl radical scavengers, but was independent of the scavenger concentration, and this suggests that free hydroxyl radical is not involved in the oxidation of DCFH in this system. Superoxide anion did not directly oxidize DCFH. Data suggest that H2O2-Fe(2+)-derived oxidant is mainly responsible for the nonenzymatic oxidation of DCFH. In addition, peroxidase alone and oxidants formed during the reduction of H2O2 by peroxidase oxidize DCFH. Since DCFH oxidation may be derived from several reactive intermediates, interpretation of specific reactive oxygen species involved in biological systems should be approached with caution. However, DCFH remains an attractive probe as an overall index of oxidative stress in toxicological phenomena.
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PMID:Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. 132 37

Peroxidation of rat liver microsomes and of phospholipid isolated from them was studied using iron(III) and ascorbate initiation. One-half equivalent of citrate per iron equivalent maintained solubility of the metal ion at neutral pH. Several metal chelators, including additional citrate, blocked peroxidation, but catalase did not. These characteristics are consistent with those reported by others (D. M. Miller and S. D. Aust (1989) Arch. Biochem. Biophys. 271, 113-119). Several antioxidants, principally tocopherol analogues and nitroxides, and, as well, a nonenzymatic component of "thymol-free" catalase, potently blocked lipid peroxidation, or, equivalently, dioxygen depletion from suspensions of peroxidizing microsomes. Chromanols were the most active antioxidants. No thiol studied had significant antioxidant activity in the test system.
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PMID:Inhibition of lipid peroxidation promoted by iron(III) and ascorbate. 132 41

Evidence is presented that the nitroxide free radical, TEMPO, at concentrations commonly used to prevent oxidative damage, increases the intracellular hydrogen peroxide concentration. To investigate the origin of this increased hydrogen peroxide concentration, we have incubated various human tumor cell lines with compounds interfering with the generation of active oxygen metabolites. Sodium azide, inhibitor of the respiratory chain, the iron-chelating agent desferrioxamine, superoxide dismutase and catalase had no effect on the hydrogen peroxide concentration. Metyrapone, inhibitor of the cytochrome P450 system, was demonstrated to decrease, but not completely prevent, the hydrogen peroxide production. N-ethylmaleimide, a sulphydryl-bond alkylating agent, was able to completely prevent the increased hydrogen peroxide production. We conclude that, by increasing the cellular hydrogen peroxide concentration, TEMPO exerts a pro-oxidant effect. This increase in hydrogen peroxide production seems to be mediated by the induction of oxidase activity in the cytochrome P450 system, but other cellular systems involved in electron transport may also play a role.
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PMID:Increased hydrogen peroxide concentration in human tumor cells due to a nitroxide free radical. 132 9

Nifedipine, which is unstable at light, is photolytically converted to the corresponding 4-[2'-nitrosophenyl]-pyridine (NTP). We reported earlier that NTP react with unsaturated lipids in a pseudo Diels-Alder reaction, thus forming stable nitroxide radicals. In this paper we report that superoxide is being generated in the latter reaction. Superoxide formation was evidenced by SOD-inhibitable cytochrome c reduction in the reaction of NTP with egg phosphatidylcholine at molar ratio 1:1, and 1:3. In this reaction an ESR-observable nitroxide radical was formed. Maximum nitroxide formation was observed after 90 min; the addition of SOD (93 units/ml) increased the concentration of nitroxide. This effect of SOD was reversed by catalase, indicating involvement of hydrogen peroxide in this effect. The nitroxide radical formation appears to be metal-independent, since neither iron salts, nor an iron chelator, desferal, influenced the nitroxide formation. Although production of superoxide in our system was only observed at high concentrations of NTP and of unsaturated lipids, this reaction may be of potential cytotoxic significance due to redox cycling of the nitroxide/hydroxylamine couple in cellular systems.
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PMID:Formation of superoxide in the reaction of photolytically altered nifedipine--a nitroso compound--with unsaturated membrane lipids. 132 24


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