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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Artemisinin is an effective antimalarial agent, and its action on the malarial parasite is suggested to be mediated by oxidative processes. Since malarial parasites contain a high concentration of hemin, and hemin may induce the formation of reactive oxygen species, we investigated the interaction of artemisinin, iron and hemin. We used erythrocyte membrane-bound Ca2+ pump ATPase (basal) and calmodulin (CaM)-activated Ca2+ pump ATPase as our model. Membranes were incubated with artemisinin in the presence or absence of iron-ascorbate or hemin at 37 degrees for 1 hr. Following incubation, ATPase activity was measured. Our results showed that artemisinin (500 microM) had no effect on ATPase activities. However, artemisinin enhanced the inhibitory effect of iron (50 microM)-ascorbate (500 microM) on ATPase activity (46.3 +/- 3.9 vs 63 +/- 2.1% for basal; 57.2 +/- 2.5 vs 74.8 +/- 2.1% for CaM-activated). Desferrioxamine (DFO, 200 microM) blocked significantly the effect of iron-ascorbate-artemisinin on ATPases (P < 0.01). Hemin inhibited ATPase activity in a concentration-dependent fashion. Artemisinin enhanced hemin (10 microM)-induced inhibition of basal (36.0 +/- 6.0 vs 73.7 +/- 3.0%) and CaM-activated Ca2+ pump ATPase (31.6 +/- 2.8 vs 70.0 +/- 1.5%). Iron chelators (DFO, ferene, 8-hydroxyquinoline, 1,10-phenanthroline, and 1,2-dimethyl-3-hydroxypyrid-4-one) had no effect on artemisinin plus hemin-induced enzyme inhibition. Catalase (2000 U/mL) had a minor effect on the artemisinin-hemin or hemin-mediated effect. Thiourea (1 mM) had no effect. However, superoxide dismutase (500 U/mL) and dithiothreitol blocked artemisinin-hemin or hemin-mediated ATPase inhibition significantly (P < 0.001). In conclusion, these results suggest that, in our model, artemisinin enhances the damage of hemin-induced ATPases via oxidation of thiol groups on the enzymes. Free iron or hydroxyl radical does not seem to be involved. This interaction between artemisinin and hemin may contribute to the antimalarial action of artemisinin against malarial parasites.
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PMID:Enhancement of hemin-induced membrane damage by artemisinin. 808 Apr 46

When Escherichia coli was incubated with xanthine oxidase and acetaldehyde, the killing of E. coli was accelerated by iron-EDTA but inhibited by hematin or hemoglobin. On the other hand, when E. coli was incubated with human neutrophils in the presence of phorbol myristate acetate (PMA), all of these iron species at concentrations of a few micromolar accelerated the inactivation of neutrophils and in so doing protected the E. coli from being killed by the neutrophils. The inactivation of the neutrophils was accompanied by an increase in lipid peroxidation and by a decrease in viability measured with trypan blue. This inactivation was inhibited by scavengers such as deoxyribose, mannitol, or thiourea. Desferrioxamine B and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) both inhibited the inactivation mediated by iron-EDTA, but had no effect on the hematin- or hemoglobin-mediated inactivation. Vanadium (vanadyl ion), an effective Fenton reagent, behaved in the same way as iron-EDTA relative to the effects of DMPO on neutrophil inactivation. These results led us to conclude that neutrophils were inactivated during PMA stimulation by OH radicals in the presence of iron-EDTA and by some other oxidizing species when hematin or Hb is present. Ascorbate enhanced the inactivation of neutrophils mediated by these iron species. Catalase was very effective in inhibiting neutrophil inactivation. Superoxide dismutase was not as effective but the combination with catalase was most effective.
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PMID:The effect of hemoglobin, hematin, and iron on neutrophil inactivation in superoxide generating systems. 813 43

The effect of iron-overload on rat kidney was studied after a single injection of iron-dextran. Total iron content in kidney and isolated kidney mitochondria was markedly elevated over control values. To assess mitochondrial damage by iron overload, succinate-cytochrome c reductase and NADH-cytochrome c reductase activities as well as the rate of succinate-dependent hydrogen peroxide generation were measured. None of these activities were significantly affected by acute iron overload. The net content and the rate of TBARS (thiobarbituric acid reactive species) formation in kidney homogenates from iron-treated rats was significantly higher than that of control animals. Total superoxide dismutase activity in the homogenates from iron overloaded kidney was decreased by 26%, as compared to controls. Catalase, glutathione peroxidase, and Mn-superoxide dismutase activities were not affected by the treatment. The content of alpha-tocopherol was consistently decreased in whole kidney homogenates (-31%), mitochondria from kidney medulla (-31%) and cortex (-34%), from iron-overloaded rats. Our data suggest that iron dextran treatment does not affect kidney integrity, even though increases in lipid peroxidation occur. Vitamin E appears to be effective in controlling iron-dextran dependent radical generation in kidney.
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PMID:Resistance of rat kidney mitochondrial membranes to oxidation induced by acute iron overload. 816 Jan 95

lambda DNA strand breaks were easily induced in a reaction system involving alloxan with reduced glutathione (GSH) in the presence of FeCl3 in a HEPES-NaOH buffer, pH 7.4. Increasing concentrations of FeCl3 in the reaction system caused DNA strand breaks in a concentration-dependent fashion, suggesting that iron is required to induce the DNA strand breaks. Catalase, scavengers of hydroxyl radicals (HO.) and iron-chelators almost completely inhibited the DNA strand breaks, but superoxide dismutase (SOD) did not do so, suggesting that the HO., formed by a Fenton-type reaction, was the species responsible for the DNA strand breaks. The addition of FeCl3 to the solution containing DNA caused the formation of a DNA-Fe(III) complex, in which Fe(III) was reduced by an alloxan radical (HA.) but not by a superoxide radical. Only when apotransferrin was added to the reaction mixtures before the addition of FeCl3, were both the DNA strand breaks and the reduction of Fe(III) strongly inhibited. These results suggest that the Fe(III) bound to DNA catalyzes the DNA strand breaks which may be caused by the generation of site-specific HO. via an HA.-dependent Fenton-type reaction.
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PMID:A role of iron in lambda DNA strand breaks in the reaction system of alloxan with reduced glutathione: iron(III) binding to the DNA. 820 21

Iron, presumably by participating in generation of hydroxyl radical or other oxidant species or initiation of lipid peroxidation, has been shown to play an important role in several models of tissue injury, including acute renal failure induced by the antibiotic gentamicin. However, the sources of iron remain unknown. Rat renal mitochondria incubated at 37 degrees C with gentamicin resulted in a time- (15-60 min) and a dose-dependent (0.01-5 mM) iron release as measured by formation of iron-bathophenanthroline sulfonate complex FeII-(BPS)3 [at 60 min, control: 1.2 +/- 0.1 nmol/mg protein, n = 7; gentamicin (5 mM): 5.1 +/- 0.4 nmol/mg protein, n = 7]. No formation of FeII(BPS)3 complex was detected in the absence of mitochondria or when incubations were carried out at 0 degrees C. Similar results were obtained when 2,2'-dipyridyl, another iron chelator, was used for measurement of iron release. On the basis on our previous study that gentamicin enhances generation of hydrogen peroxide by renal cortical mitochondria, we examined whether effect of gentamicin on iron release is mediated by hydrogen peroxide. Catalase (which decomposes hydrogen peroxide), but not heat-inactivated catalase, as well as pyruvate, a potent scavenger of hydrogen peroxide, prevented gentamicin-induced iron mobilization. Superoxide dismutase, a scavenger of superoxide anion, or hydroxyl radical scavengers (dimethylthiourea or sodium benzoate) had no effect. Taken together, the data with scavengers indicate that gentamicin-induced iron mobilization from mitochondria is mediated by hydrogen peroxide.
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PMID:Gentamicin-induced mobilization of iron from renal cortical mitochondria. 821 3

The extent of DNA damage and lipid peroxidation induced by myricetin, a polyphenolic flavonoid, were studied in isolated rat liver nuclei under aerobic conditions. Myricetin induced significant (P < 0.05) concentration-dependent nuclear DNA degradation concurrent with lipid peroxidation; these effects were enhanced by iron (III) or copper (II). Catalase, superoxide dismutase (SOD), mannitol and sodium azide did not inhibit myricetin-induced nuclear DNA damage in the presence of iron (III) or copper (II). However, all of these antioxidants stimulated myricetin-induced DNA damage in the presence of copper (II). Lipid peroxidation induced by myricetin was significantly inhibited only by SOD in the presence of copper (II), whereas it was enhanced by catalase and sodium azide in the presence of iron (III). These results demonstrate the pro-oxidant properties of polyphenolic flavonoids, which are generally considered to be antioxidants and anticarcinogens, and suggest a dual role for these flavonoids in mutagenesis and carcinogenesis.
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PMID:Interactions of flavonoids, trace metals, and oxygen: nuclear DNA damage and lipid peroxidation induced by myricetin. 833 Mar 5

There is evidence that reperfusion injury of cardiac tissue may be caused by the generation of oxygen-derived free radicals and oxidants and by the induction of intracellular calcium overload, although the relation between these two mechanisms of injury is uncertain. In addition, the relation between the types of cellular injury and specific active species is unclear. In an attempt to resolve these problems, we investigated the effects of oxygen radicals and oxidants, which are purportedly generated during reperfusion after prolonged ischemia, and various antioxidants on contractility and morphology of cultured fetal mouse cardiac myocytes. Xanthine oxidase in the presence of xanthine, H2O2, HOCl, and NH2Cl induced cessation of spontaneous beating followed by cessation of electrical stimulation-elicited beating but did not induce an increase in [Ca2+]i. After prolonged incubation with xanthine oxidase + xanthine and H2O2, the cardiac myocytes showed morphological degeneration (at least 80% of the cells developed hypercontraction) with a concomitant increase in [Ca2+]i. These observations suggest that contractile impairment does not result in an increase of [Ca2+]i, but hypercontraction does. Catalase, but not superoxide dismutase, protected the cultured cardiac myocytes against xanthine oxidase + xanthine- and H2O2-induced contractile and morphological impairment. In the light of this observation, we hypothesize that the superoxide anion is not responsible for these types of impairment. Addition of dimethylthiourea (an .OH scavenger) and intracellular preloading with deferoxamine (an iron chelator) protected the myocytes against H2O2-induced contractile and morphological damage, but intracellular preloading with iron enhanced it. These observations led us to hypothesize that intracellularly generated .OH may be a mediator of H2O2-induced injury to cultured cardiac myocytes. In addition, we observed that H2O2 itself induced cessation of spontaneous but not electrical stimulation-elicited beating.
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PMID:Contractile and morphological impairment of cultured fetal mouse myocytes induced by oxygen radicals and oxidants. Correlation with intracellular Ca2+ concentration. 839 8

The relative risk of primary hepatocellular carcinoma in genetic hemochromatosis (GH) is estimated at over 200 times as that of control populations. Recently, ferric ion chelated to citrate (Fe-citrate) was identified as the major non-transferrin-bound iron in the serum of GH patients. We investigated whether low concentration of Fe-citrate plus reductant could damage supercoiled plasmid DNA under physiological pH and ionic strength. Incubation of Fe-citrate with either H2O2, L-ascorbate, or L-cysteine induced single- and double-strand breaks in supercoiled plasmid pZ189 in a concentration- and time-dependent fashion. DNA strand breaks produced by Fe-citrate plus H2O2 increased at reduced pH (< or = 6.9). Catalase and free radical scavengers inhibited the DNA breakage produced by Fe-citrate in combination with each reductant, suggesting that H2O2 and finally .OH are responsible DNA damaging species. The catalytic ability of Fe-citrate to induce DNA strand breaks, particularly double-strand breaks (DSBs), may contribute to the carcinogenic processes observed in GH.
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PMID:Induction of oxidative single- and double-strand breaks in DNA by ferric citrate. 839 39

The decay of nitroxide spin label electron paramagnetic resonance (EPR) absorption intensity was used to investigate the doxorubicin-mediated intracellular generation of free radicals. The effects of 50-500 micrograms/ml doxorubicin on human tumor cells (MCF-7, breast cancer cells, and HL-60, promyelocytic leukemia, cells) were studied by measuring 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) absorption intensity decay (TAID) at a TEMPO concentration of 10 microM. Doxorubicin accelerated the TAID in both cell lines with a detection limit of 50 micrograms/ml for MCF-7 cells and 500 micrograms/ml doxorubicin for HL-60 cells. Preincubation of cells with the iron chelating agent, deferoxamine (5 mM), partially prevented the effects of doxorubicin on the TAID. Catalase and copper, zinc-superoxide dismutase (Cu,Zn-SOD) had no influence on the effects of doxorubicin on the TAID in intact cells. However, Cu,Zn-SOD completely abolished the effects of doxorubicin on the TAID in a MCF-7 cell-free system. Our findings suggest that doxorubicin mediates the intracellular generation of O2.- and that iron is involved in this process.
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PMID:Doxorubicin-mediated free radical generation in intact human tumor cells enhances nitroxide electron paramagnetic resonance absorption intensity decay. 841 98

Direct oxidative protein damage by iron-nitrilotriacetate (NTA), as well as physiological iron complexes, iron-citrate and iron-ADP was studied in the presence or absence of H2O2, using bovine serum albumin (BSA), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GSSGRase) and catalase as the target proteins. Both Fe(III)NTA+H2O2 and Fe(II)NTA+H2O2 caused marked BSA fragmentation which accompanied the decrease in the intrinsic tryptophan fluorescence and appearance of bityrosine fluorescence. However, Fe(III)citrate+H2O2 showed only slight BSA fragmentation. In the absence of H2O2, Fe(II) NTA but not Fe(III)NTA caused similar but slight BSA fragmentation, which depended on the molecular oxygen. Fe(II)citrate also showed O2-dependent BSA fragmentation to a comparable degree, however, Fe(II)ADP showed no detectable BSA damage. BSA fragmentation by Fe(II)NTA+O2 and by Fe(III)NTA+H2O2 resulted in the appearance of the new alpha-amino groups. Electron spin resonance study using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping reagent showed DMPO-OH spin adduct, which suggests the presence of hydroxyl radical, in Fe(III)NTA+H2O2, but not in Fe(II)NTA+O2 system. Fe(II)NTA inactivated G-6-PD and GSSGRase in a O2-dependent manner, however, G-6-PD was more susceptible to the damage. This enzyme inactivation also accompanied the protein fragmentation and was not due to simple sulfhydryl oxidation. Catalase was not significantly inactivated nor fragmented by Fe(II)NTA+O2. These findings suggest that the interaction between proteins and iron-chelate complexes is important in iron catalyzed oxidative damage, and that the structure of the chelating agent may determine the target molecules.
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PMID:Oxidative damage of bovine serum albumin and other enzyme proteins by iron-chelate complexes. 854 12


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