Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron was released from ferritin by the catecholamine analog, 6-hydroxydopamine. Iron release was more efficient under nitrogen than in air, suggesting that the hydroquinone has the major role in the process. Superoxide dismutase, alone or in combination with catalase, strongly inhibited 6-hydroxydopamine oxidation and greatly enhanced the amount of ferritin iron release. Catalase alone had a similar, but lesser effect. Iron released from ferritin accelerated the autoxidation of 6-hydroxydopamine. This occurred by a mechanism that was inhibited by a combination of catalase and a chelator, and to a lesser extent by superoxide dismutase. 6-Hydroxydopamine was a good promoter of metal-catalysed lipid peroxidation, and ferritin-iron participated in the process. Superoxide dismutase, and to a lesser extent catalase, stimulated peroxidation catalysed by adventitious levels of iron, but in the presence of ferritin, each enzyme was inhibitory. It appears that the greatly enhanced iron release seen under these conditions accelerated the autoxidation of 6-hydroxydopamine so that less was available to participate in peroxidative reactions. However, when 6-hydroxydopamine autoxidation was prevented by a combination of superoxide dismutase and catalase, lipid peroxidation was also inhibited, suggesting that some intermediate of autoxidation is a further requirement for the process.
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PMID:6-Hydroxydopamine releases iron from ferritin and promotes ferritin-dependent lipid peroxidation. 251 34

The major objective of the present study was to characterize the sequence of events leading to endothelial cytotoxicity induced by oxidants generated extracellularly by xanthine oxidase. 51Cr-labeled monolayers of calf pulmonary artery endothelial cells were exposed to a reaction mixture containing hypoxanthine, xanthine oxidase, and chelated iron (HX/XO) and endothelial cell injury was quantitated as 51Cr release into the media. Catalase, but not mannitol or superoxide dismutase, prevented endothelial cell injury induced by HX/XO, indicating that H2O2 was the mediator of the cytotoxicity. Pretreatment of the cells with free deferoxamine (an iron chelator), but not with deferoxamine bound to dextran (mol wt 40,000), prevented endothelial cell injury induced by HX/XO or H2O2. Of the membrane-permeant hydroxyl radical scavengers dimethylsulfoxide and dimethylthiourea, only dimethylthiourea prevented 1) HX/XO or H2O2-induced endothelial cytotoxicity and 2) deoxyribose degradation by hydroxyl radicals (.OH) generated by an iron-catalyzed reaction on the sugar (site-specific reaction). The concentration of ferritin required to produce significant quantities of .OH was much greater than that present in endothelial cells, and ferritin-catalyzed .OH formation was not affected by deferoxamine, indicating that ferritin-bound iron is most likely not the physiologically active catalyst. We conclude that extracellularly generated H2O2 can enter the cell and interact with nonferritin iron to produce the cytotoxic .OH via a site-specific reaction.
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PMID:Xanthine oxidase-induced injury to endothelium: role of intracellular iron and hydroxyl radical. 255 49

Release of iron from ferritin by the polyhydroxypyrimidines, dialuric acid, isouramil, divicine, and acid-hydrolyzed vicine, was measured. Iron was released at fast initial rates which gradually declined to zero in 10 min. All the compounds were better reductants for ferritin-iron under nitrogen than in air. The effects of superoxide dismutase, catalase, and glutathione on both initial rates and total iron released over 30 min in air were determined. Major effects were inhibition by superoxide dismutase for divicine and isouramil and enhancement for dialuric acid and acid-hydrolyzed vicine. Glutathione promoted increased iron release that was further enhanced by superoxide dismutase. These increases were particularly striking over the longer time period. Catalase, in all cases, gave modest enhancement. Enhanced iron release correlated with inhibition of pyrimidine oxidation. The results indicate that the reduced form of each pyrimidine releases ferritin iron directly, and the effects of the antioxidants are mainly to maintain or regenerate the reduced pyrimidines. A combination of each pyrimidine and ferritin caused peroxidation of phopholipid liposomes, above that seen with the pyrimidines and adventitious iron. Glutathione, superoxide dismutase, and catalase modulated lipid peroxidation in a way consistent with their effects being mainly on ferritin-iron release. On the basis of our findings, we propose that the release and subsequent reactions of ferritin-iron may contribute to the toxicity of these compounds. Although glutathione and superoxide dismutase together efficiently inhibit redox cycling and H2O2 production from the pyrimidines, this combination maximized iron release from ferritin and ferritin-dependent lipid peroxidation.
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PMID:Release of iron from ferritin by divicine, isouramil, acid-hydrolyzed vicine, and dialuric acid and initiation of lipid peroxidation. 273 3

Oxidative deposition of iron in ferritin or the autoxidation of iron in the absence of protein produces radicals from Good's buffers. Radical species are formed from the piperazine ring-based buffers Hepes (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), Epps 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid, and Pipes 1,4-piperazinediethanesulfonic acid, but not from Mes (4-morpholineethanesulfonic acid) which contains a morpholine ring. The radicals all have half-lives around 10 min and display very similar electron paramagnetic resonance spectra consisting of at least 30 lines. The Hepes radical can be formed by the addition of potassium superoxide directly to the buffer and its production during iron(II) autoxidation is inhibited by superoxide dismutase (EC 1.15.1.1). Catalase (EC 1.11.1.6) accelerates the decay of the EPR spectrum. Thus the buffer radicals are secondary radical species produced from oxygen radicals formed during the iron catalyzed Haber-Weiss process. The deoxyribose/thiobarbituric acid assay for hydroxyl radical production shows that Hepes is an effective hydroxyl radical scavenging agent. The Hepes radical can also be formed electrolytically at a potential of +0.8 V (vs standard hydrogen electrode). Oxidation of Hepes at pH 10 during the autoxidation of iron(II) or by the addition of hydrogen peroxide produces a nitroxide radical. These results indicate that piperazine ring Good buffers should be avoided in studies of redox processes in biochemistry.
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PMID:Radicals from "Good's" buffers. 284 86

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.
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PMID:Ferritin and superoxide-dependent lipid peroxidation. 298 54

During inflammation, the superoxide anion (O-2) and hydrogen peroxide (H2O2) are produced by stimulated polymorphonuclear leukocytes and macrophages. The toxic effects of these reactive oxygen intermediates increase when traces of iron are present, because iron catalyzes the formation of the hydroxyl radical (OH.). Partially saturated iron-binding proteins, such as transferrin and ferritin, are unable to catalyze OH. formation in vitro. Mobilization of iron from these proteins is necessary for iron stimulation of OH. formation. This paper reports that stimulated polymorphonuclear leukocytes mobilize iron from human and horse ferritin, but not from human transferrin. Iron release from ferritin depends on O-2 because it can be prevented by the addition of superoxide dismutase. Catalase and dimethylsulfoxide have no inhibitory effect on iron mobilization. The efficiency of the iron release increases at low levels of O-2 production. Only O-2 produced by granulocytes is sufficient for iron mobilization, because solid potassium superoxide is also able to release iron from ferritin. We propose that this reaction may potentiate the formation of the OH. radical in inflammatory states.
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PMID:Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases. 632 64

Ferritin from horse spleen was found to cause severe chromosome aberrations in cultured Chinese hamster ovary cells. Ferritin at 15 to 170 microgram/ml was clastogenic and at higher doses was cytotoxic. At comparable concentrations of protein or iron, neither apoferritin nor complexed iron was clastogenic. Sulfhydryl compounds glutathione and cysteine reduced the cytotoxic and clastogenic activities of ferritin. Physiological concentrations of glutathione may normally be sufficient to protect cells from damage. The reducing agent ascorbate had little protective effect. Chelating agents varied in their inhibitory activity: ethylenediaminetetraacetic acid (hexadentate) greater than nitrilotriacetic acid (tetradentate) greater than salicylate (bidentate). 2,2'-Bipyridyl enhance the chromosome-damaging action of ferritin while histidine did not markedly alter the frequencies of aberrations. Catalase and superoxide dismutase showed no inhibitory activity. The mechanism of DNA damage may involve reduction of Fe(III) in the ferritin core to Fe(II), followed by reoxidation of Fe(II) with possible formation of free radicals.
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PMID:Chromosome-damaging activity of ferritin and its relation to chelation and reduction of iron. 719 42

The choriocapillaris is the fenestrated capillary bed in the choroid of the eye and is the major blood supply to the retinal pigment epithelium (RPE) and photoreceptor cells. Bruch's membrane (BM) is a multilaminated basement membrane that separates the choriocapillaris from the RPE. In a previous study (Pino RM, Essner E; Cell Tissue Res 208:21, 1980) we found that the choriocapillary endothelium restricted the egress of ferritin from the choriocapillaris. In the present study, hemeproteins were used to further establish the permeability characteristics of this capillary bed. Horseradish peroxidase (Einstein-Strokes radius (ESR), 30 A) rapidly crossed the capillary endothelium (less than 5 min) after intravenous administration and after 5 minutes filled BM and the basal infoldings of the RPE. In contrast, hemoglobin (Hg) (ESR, 32 A) and lactoperoxidase (LP) (ESR, approximately 40 A) are markedly restricted at the level of endothelial diaphragmed fenestrae, channels, and intercellular junctions. Little vesicular transport of these proteins was observed. The reaction product of the two hemeprotein activities was not demonstrable in BM for up to 30 min after injection; relatively low levels were detected after 75 min. HG and LP appear to be further restricted by BM, since their reaction products were not demonstrable between the RPE basal infoldings at this time. Catalase (ESR, 52 A) activity was not detected in BM for up to 4 hr after injection. These results indicate that the rat choriocapillary endothelium, unlike the fenestrated endothelia lining other vascular beds, substantially restricts the passage of large tracer molecules.
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PMID:Permeability of rat choriocapillaris to hemeproteins. Restriction of tracers by a fenestrated endothelium. 725 21

The incubation of lambda DNA in the reaction system of alloxan plus NADPH-cytochrome P450 reductase (fp2) in the presence of ferritin caused strand breaks after a lag time of about 5 min. Addition of ferritin to the reaction system at concentrations below 50 micrograms/ml caused the strand breaks of DNA in a concentration-dependent fashion. Catalase, scavengers of hydroxyl radicals (HO.) and iron-chelators almost completely inhibited the DNA strand breaks, but superoxide dismutase (SOD) did not, suggesting that the strand breaks are induced by the generation of HO. via the reaction of H2O2 and Fe(II), namely, the Fenton reaction. When the ferritin was incubated in the reaction system of alloxan plus fp2, the iron release from ferritin increased with incubation time depending on the amount of fp2. The addition of increasing concentrations of ferritin to the reaction system resulted in progressive increase in the iron release and a decrease in the electron spin resonance signal intensity of alloxan radical (HA.), the one electron reduced form of alloxan, suggesting that HA. generated in the reaction system is capable of releasing iron from ferritin. These results support the possibility that the iron released from ferritin may be involved in the diabetogenic action of alloxan.
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PMID:Effect of ferritin on lambda DNA strand breaks in the reaction system of alloxan plus NADPH-cytochrome P450 reductase: ferritin's role in diabetogenic action of alloxan. 774 95

Ferritin is the major storage form of iron within cells, and iron released from ferritin has been shown to stimulate lipid peroxidation. Microsomes from rats chronically fed ethanol are more active in generating reactive oxygen intermediates than control microsomes. Since superoxide is one of the reductants capable of releasing iron from ferritin, and superoxide generation by microsomes is increased after chronic ethanol treatment, the ability of ferritin to stimulate lipid peroxidation of microsomes isolated from control rats and rats treated chronically with ethanol was evaluated. Ferritin was much more effective in stimulating lipid peroxidation of microsomes after ethanol treatment; net increases in thiobarbituric acid-reactive components by ferritin were 4-fold greater in the presence of NADPH with microsomes from the ethanol-treated rats compared to pair-fed controls and 10-fold greater with NADH as the microsomal reductant. Net increases in chemiluminescence by ferritin were about 10-fold greater with microsomes from the ethanol-treated rats. The NADPH- and NADH-dependent increases in lipid peroxidation produced by ferritin were prevented by superoxide dismutase, which lowered the rates found in the presence of ferritin to values found in the absence of ferritin. Catalase and hydroxyl radical scavengers had no effect on the stimulation by ferritin. Nonheme iron chelators prevented the ferritin stimulation as did glutathione, propylgallate, and trolox. Basal rates of lipid peroxidation were inhibited by anti-CYP2E1 IgG; the stimulation by ferritin was decreased by anti-CYP2E1 IgG. These results show that microsomes from ethanol-fed rats are more reactive than control microsomes in interacting with ferritin to produce oxidants capable of catalyzing lipid peroxidation. The inhibition of the ferritin-catalyzed lipid peroxidation by superoxide dismutase and anti-CYP2E1 IgG is consistent with a role for CYP2E1-generated superoxide radical in mobilizing iron from ferritin and in the subsequent catalysis of lipid peroxidation. Since ferritin is the major cellular storage form of iron, increased mobilization of iron from ferritin by CYP2E1-derived superoxide radical may play a role in the development of oxidative stress after ethanol treatment.
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PMID:Ferritin stimulation of lipid peroxidation by microsomes after chronic ethanol treatment: role of cytochrome P4502E1. 880 16


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