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)

Restriction of energy intake (ER), without malnutrition of essential nutrients, has repeatedly been demonstrated to increase longevity in rodents. In the antioxidant theory of aging the lack of balance between the generation of free radicals and free radical scavenging was thought to be a main causal agent, in the aging process. From this point of view the antiaging effect induced by ER might be due to the lower rate of free-radical production and related damage induced by a lower metabolic rate. The antiaging effects of ER might also occur in humans. This study explored the effects of a 10-week moderately energy-restricted diet (80% of habitual) in 24 non-obese middle-aged men (16 ER subjects, 8 controls) on resting metabolic rate (RMR) and indicators of the primary antioxidant defense system, oxidative stress and genotoxicity. RMR decreased significantly in both groups, even when adjustments were made for the change in body composition. The increase in blood vitamin C concentration correlated with the increase in urinary 8-hydroxydeoxyguanosine (80HdG) excretion. The change in urinary 80HdG excretion also correlated with the change in RMR per kg fat-free mass. No differences between groups were found for changes in indicators of genotoxicity, erythrocyte catalase, glutathione peroxidase and superoxide dismutase activity and in plasma vitamin E, A or beta-carotene concentrations. We conclude that 10 weeks of moderate ER did not affect indicators of antioxidative capacity, oxidative stress and genotoxicity of humans. Since subjects were not in energy balance at the end of the study, no conclusions can be made with respect to long-term effects.
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PMID:Short-term moderate energy restriction does not affect indicators of oxidative stress and genotoxicity in humans. 756

The generation of 8-hydroxydeoxyguanosine (8OHdG) in calf thymus DNA treated with O-phenylphenol (OPP) or its major metabolites, phenylhydroquinone (PHQ) and phenylbenzoquinone (PBQ), was studied. The content of 8OHdG residues was increased in DNA treated with PHQ, and the generation of 8OHdG was highly dependent on PHQ concentration. PBQ had little effect on the formation of 8OHdG, and OPP had no effect. The formation of 8OHdG by PHQ was reduced by oxygen radical scavengers such as catalase, sodium benzoate and sodium azide. The PHQ-induced 8OHdG formation was accelerated by the addition of CuCl or CuCl2 to the reaction mixture, but was decreased by the addition of chelating agents such as EDTA, bathocuproinedisulfonic acid disodium salt (bathocuproine disulfonate) and O-phenanthroline. These results demonstrate that hydroxyl radicals generated in the process of oxidation of PHQ contribute to the formation of 8OHdG in DNA, and copper ions facilitate the oxidative DNA damage. Copper ions greatly accelerated the PHQ-induced DNA cleavage in vitro, although they had no effect on cleavage without PHQ. On the other hand, DNA cleavage occurred by the addition of FeCl2 in the absence and presence of PHQ. FeCl2 stimulates 8OHdG formation only slightly with or without PHQ. Furthermore, the stimulatory effect of FeCl2 on 8OHdG formation was observed even in the presence of EDTA. The formation of 8OHdG in bladder DNA is likely to be one of a series of events leading to bladder tumors seen in rats fed OPP-containing diet.
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PMID:Formation of 8-hydroxydeoxyguanosine in calf thymus DNA treated in vitro with phenylhydroquinone, the major metabolite of O-phenylphenol. 772 64

The objective of this study was to elucidate the nature of the mechanisms by which overexpression of copper- and zinc-containing superoxide dismutase (Cu,Zn-SOD) and catalase extends life span of Drosophila melanogaster. Experimental flies containing single extra doses of Drosophila Cu,Zn-SOD and catalase genes were compared with appropriate controls at different ages. Overexpression of Cu,Zn-SOD and catalase caused a retardation in the accumulation of 8-hydroxydeoxyguanosine during aging and in response to the exposure of live flies to x-rays. The age-related loss of glucose-6-phosphate dehydrogenase activity (Glu-6-P dehydrogenase) and the increase in the rate of mitochondrial H2O2 generation were less steep in the experimental than control flies. The rate of in vivo oxygen consumption in the latter two-thirds of life span was higher in the experimental than in the control flies. Furthermore, the metabolic potential, or the total amount of oxygen consumed during an average life span, was about 30% greater in the experimental than the control flies. Altogether, results of this study indicate that overexpression of Cu,Zn-SOD and catalase ameliorates the age-related accumulation of molecular oxidative damage and susceptibility to such damage in response to acute oxidative stress while prolonging the metabolic life of flies. The concept that oxidative stress is a causal factor in the aging process is supported.
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PMID:Simultaneous overexpression of copper- and zinc-containing superoxide dismutase and catalase retards age-related oxidative damage and increases metabolic potential in Drosophila melanogaster. 779 67

The modified DNA base 8-hydroxyguanine has been implicated in spontaneous mutagenesis, carcinogenesis and cellular aging. Polyclonal antibodies specific for the 8-hydroxy-2'-deoxyguanosine moiety in oxidized DNA were used for sensitive detection and quantitation of this biomarker of oxidative damage to cellular DNA. The analysis was performed with immunoslot blot assay (ISB) of oxidized DNA modified in vitro with methylene blue plus light and upon H2O2 treatment of cultured human cells. The level of 8-OHdG in DNA exposed to 90 and 120 min light in the presence of 100 microM methylene blue showed 15.96 +/- 2.4 and 22.65 +/- 3.65 pmol/micrograms DNA compared to 0.107 +/- 0.024 pmol/micrograms in commercial calf thymus DNA control. Inherent damage, due to cellular endogenous oxidation of DNA, increased significantly upon inhibition of catalase activity in human cells with 10 mM azide. The damage increased further on exposure of azide-treated cells to H2O2. The amounts of 8-OHdG following treatment of cells with 10 and 100 microM H2O2 were determined to be 205 +/- 42 and 333 +/- 17.5 pmol/micrograms DNA respectively. Very low but quantifiable antibody binding was seen with the 'control unoxidized' human nuclear DNA. This DNA, obtained under controlled conditions to restrict the induction of 8-OHdG during isolation, provides a background level of 0.022 +/- 0.005 pmol 8-OHdG/micrograms DNA. The quantitative assessment of 8-OHdG by ISB assay, with fmol sensitivity and direct analysis using unhydrolyzed DNA, should prove a highly valuable alternative to currently used approaches to detecting 8-OHdG in enzymatic DNA hydrolysates.
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PMID:Quantitative immunoanalysis of promutagenic 8-hydroxy-2'-deoxyguanosine in oxidized DNA. 792 99

We have established a system in which a human cell line generated reactive oxygen species (ROS), using a dimethyl sulfoxide-differentiated promyelocytic leukemia cell line HL60 (DMSO-HL60), which has characteristics similar to those of human neutrophils. DMSO-HL60 generated O2- upon stimulation with a tumor promoter, phorbol myristate acetate (PMA). O2- generation, determined as O2- release from the PMA-stimulated cells by the reduction of cytochrome c, was dependent on the dose of PMA and reached almost maximal with 2.0 nM PMA. PMA dose-dependently increased 8-hydroxydeoxyguanosine (8OHdG) in DMSO-HL60, typical of mutagenic oxidative DNA damage. The 8OHdG level, determined by electrochemical detection with high performance liquid chromatography, also became almost maximal with 2.0 nM PMA. The amount of O2- generation and that of the 8OHdG induction by PMA in human neutrophils were similar to those in DMSO-HL60. Superoxide dismutase inhibited the 8OHdG induction by about 60%, whereas catalase, deferoxamine, or thiols inhibited it almost completely. Dilution of PMA-stimulated DMSO-HL60 decreased the concentration of ROS releasing to the media from the cells. However, it did not decrease the ROS generation per cell or the 8OHdG induction. The addition of H2O2 to unstimulated DMSO-HL60 did not increase the 8OHdG level. These findings indicate that DMSO-HL60 could be used as a substitute for human neutrophils, that the concentration of ROS is not the only determinant for the 8OHdG induction, but that it requires both acquisition of susceptibility to ROS by reduction of iron by O2- and formation of H2O2, and that ROS increase 8OHdG by attacking the ROS-generating cell.
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PMID:Establishment of a human system that generates O2- and induces 8-hydroxydeoxyguanosine, typical of oxidative DNA damage, by a tumor promotor. 795 11

Human Cu,Zn-superoxide dismutase (Cu,Zn-SOD) undergoes site-specific and random fragmentation by non-enzymic glycosylation (glycation). Released Cu2+ from the glycated Cu,Zn-SOD probably facilitates a Fenton reaction to convert H2O2 into hydroxy radical, which then participates in the non-specific fragmentation [Ookawara et al. (1992) J. Biol. Chem. 267, 18505-18510]. In the present study, we investigated the effects of glycated Cu,Zn-SOD on cloned DNA fragments and nuclear DNA and analysed the formation of 8-hydroxydeoxyguanosine (8-OH-dG). Incubation of cloned DNA fragments with Cu,Zn-SOD and reducing sugars resulted in cleavage of the DNA. The extent of the cleavage corresponded to the reducing capacity of the sugar. Metal-chelating reagents, EDTA and bathocuproine, and an H2O2 scavenger, catalase, inhibited the DNA cleavage. Hydroxy radical scavengers and aminoguanidine, an inhibitor of glycation, also inhibited the reaction. Moreover, the glycation of Cu,Zn-SOD caused the substantial formation of 8-OH-dG in DNA. When isolated nuclei were incubated with CuCl2 plus H2O2, nuclear DNA cleavage was observed. Incubation of isolated nuclei with Cu,Zn-SOD that had been pre-incubated with glucose also resulted in nuclear DNA cleavage. These results suggest that hydroxy radical is produced through a Fenton reaction by Cu2+ and H2O2 released from the glycated Cu,Zn-SOD, and participates in nuclear DNA cleavage. This mechanism may partly explain the deterioration of organs under diabetic conditions.
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PMID:DNA cleavage induced by glycation of Cu,Zn-superoxide dismutase. 799 36

Drawing upon the capacity of pyruvate to detoxify H2O2, we demonstrate that pyruvate (i) protects against H2O2-dependent, hydroxyl radical-mediated degradation of isolated DNA; (ii) reduces the amount of 8-hydroxy-2-deoxyguanosine detected following oxidative injury to isolated DNA and (iii) diminishes the amounts of detectable hydroxyl radical generated by a H2O2-dependent system. Compared to mannitol, pyruvate protects weakly against oxidative degradation of DNA induced by a H2O2-independent, hydroxyl radical-generating system. The protective effects of pyruvate against H2O2-instigated DNA damage were also evinced in cells in culture exposed to H2O2. In contrast to its protective effects against H2O2-dependent injury to DNA, pyruvate failed to offer convincing protection to another intracellular, H2O2-vulnerable target, glyceraldehyde-3-phosphate dehydrogenase. The protection conferred by pyruvate to intracellular H2O2-vulnerable targets is thus influenced by the nature of the target exposed to H2O2. Pyruvate was markedly protective in a model of cytotoxicity induced by the concomitant depletion of cellular glutathione and inhibition of catalase activity; pyruvate can thus function as an intracellular antioxidant and in this latter model, no evidence of DNA damage was observed. Pyruvate, in contrast to catalase, is a potent protector against cytotoxicity induced by organic peroxides, a finding that cannot be explained by the scavenging of organic peroxides, differences in glutathione content or attenuation in oxidative injury to DNA. We conclude that while DNA damage is a key pathogenetic event in oxidative stress induced by H2O2, such nuclear changes may not universally subserve a critical role in models of H2O2-dependent cell death. We also conclude that the antioxidant capabilities of pyruvate extend beyond scavenging of H2O2 to include potent protection against cytotoxicity induced by organic peroxides.
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PMID:Effect of pyruvate on oxidant injury to isolated and cellular DNA. 812 6

Fanconi's anemia (FA) cells are highly susceptible to both reactive oxygen species and mitomycin C (MMC), a DNA cross-linking agent. In this study we have determined the amounts of 8-hydroxydeoxyguanosine (8OHdG), typical of oxidative DNA damage, in Epstein-Barr virus transformed lymphoblasts from FA patients and normal controls by the use of HPLC combined with electrochemical detection. FA cells (HSC72 and 99 cells being assigned to FA complementation group A) formed 2-3 times more 8OHdG than control cells after incubation with 20 mM H2O2 at 37 degrees C for 30 min. FA cells also formed more 8-hydroxyguanosine, typical of oxidative RNA damage, than control cells. FA cells showed decreased activity to decompose H2O2. Although the activity in FA cells was only 20-30% less than control cells, the remaining, undecomposed H2O2 concentration was almost twice as much in FA cells as in control cells, and the remaining H2O2 concentration correlated well with the amounts of 8OHdG formation. The H2O2 decomposing activity was almost completely inhibited by sodium azide (NaN3) or aminotriazole, both catalase inhibitors. With these inhibitors the amounts of 8OHdG formation were much higher than in those cells without inhibitors, and were almost the same in control cells as in FA cells. Catalase activity in FA cell lysates was 70-80% of controls. MMC also increased 8OHdG formation in FA cells only at ED100 but not at ED50. These results indicate that FA cells, at least FA complementation group A cells, have increased susceptibility to oxidative DNA damage, and that this increased susceptibility is possibly due to decreased catalase activity. These results also suggest that catalase plays an important role in protecting DNA from oxidative damage. However, this increased susceptibility to oxidative DNA damage is considered not to be the major cause of the increased susceptibility to MMC.
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PMID:Increased formation of 8-hydroxydeoxyguanosine, an oxidative DNA damage, in lymphoblasts from Fanconi's anemia patients due to possible catalase deficiency. 838 71

The capability of Cr(III) to induce DNA lesions generated by oxidative damage was investigated in this study by examining the formation of 8-hydroxydeoxyguanosine (8-OHdG) in calf thymus DNA by CrCl3 and/or H2O2 in 10 mM phosphate buffer. In the presence of 0.5 mM H2O2, the formation of 8-OHdG markedly increased with increasing CrCl3 concentration. In contrast, H2O2 or CrCl3 alone did not cause any increase in 8-OHdG level above background. The amount of 8-OHdG induced by CrCl3 plus H2O2 was time dependent; its generation increased linearly over an incubation period of 90 min. The formation of 8-OHdG was unfavorable in an acidic solution (pH < 6); the highest level of 8-OHdG was observed at pH 7-8. Scavengers of reactive oxygen species markedly inhibited the formation of 8-OHdG by CrCl3 plus H2O2; the inhibition effect was sodium azide > D-mannitol > Tris-HCl at an equal concentration. The induction of 8-OHdG by CrCl3 plus H2O2 remained unchanged in D2O. Moreover, an addition of catalase (2.2 U/ml) to the reaction mixture completely inhibited the formation of 8-OHdG by CrCl3/H2O2, whereas only 22% of that formation was inhibited by superoxide dismutase (11 U/ml). A large amount of bovine serum albumin (1.1 mg/ml) could reduce the formation of 8-OHdG by CrCl3 plus H2O2, thereby implying that Cr(III)-mediated DNA-protein crosslinks are unfavorable for 8-OHdG formation. Furthermore, ascorbate could prevent the formation of 8-OHdG by CrCl3 plus H2O2; the extent of prevention increased with increasing ascorbate concentration (10 microM-3 mM). Thus, ascorbate acts as a free radical scavenger in the CrCl3/H2O2 system. The above findings suggest that Cr(III)/H2O2 could generate oxidative damage to DNA, possibly through a Fenton-like reaction, i.e. Cr(III)+H2O2-->Cr(IV)+.OH+OH-. This study also indicates that Cr(III), previously considered as the ultimate kinetically stable species of Cr(VI) metabolites, is capable of inducing carcinogenic lesions through interaction with a cellular oxygen species.
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PMID:Induction of 8-hydroxydeoxyguanosine in DNA by chromium(III) plus hydrogen peroxide and its prevention by scavengers. 856 17

The induction of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an index of oxidative DNA modification, was investigated in CHO-K1 cells exposed to phenyl-hydroquinone (PHQ), a major metabolite of ortho-phenylphenol (OPP), an antimicrobial. Addition of PHQ at a concentration of 50 microM to CHO cell suspensions (10(6) cells/ml) induced slight elevation of intracellular 8-OHdG levels. Pretreatment of CHO cells with 3-amino-1,2,4-triazole (AT, 20 mM) enhanced PHQ-induced 8-OHdG formation which was accompanied by cell death. Pretreatment of CHO-K1 cells with AT (20 mM) and deferoxamine (DeFe, 20 mM) inhibited the formation of 8-OHdG as well as cell death caused by PHQ. Neither AT nor DeFe affected cell viability or the formation of 8-OHdG in untreated CHO cells during the incubation period. The loss of cellular glutathione induced by the addition of PHQ alone was enhanced by the pretreatment of CHO cells with AT or AT plus DeFe. When PHQ was added to AT-pretreated cell suspensions, the concentration of PHQ decreased with time. This decrease was accompanied by the formation of phenyl-benzoquinone (PBQ). These results suggest that the reactive oxygen species derived from autoxidation of PHQ which converts to PBQ via phenyl-semiquinone elicit DNA damage in CHO cells, especially when the activity of cellular catalase is inhibited.
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PMID:Induction of 8-hydroxy-2'-deoxyguanosine in CHO-K1 cells exposed to phenyl-hydroquinone, a metabolite of ortho-phenylphenol. 862 Apr 74


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