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)

The aliphatic n-butyr-and n-valeraldehyde as well as the aromatic benz- and anisaldehyde induced DNA strand breaks in PM2 DNA in the presence of CuCl2. Neither aldehydes nor CuCl2 alone showed DNA breakage properties. The maximum of single strand breaks (SSBs) induced by the combination of CuCl2 and aldehydes was dependent on the CuCl2-concentration. The aliphatic aldehydes induced SSBs and double strand breaks (DSBs) at lower concentrations than aromatic aldehydes when optimal CuCl2 concentration were used. Catalase and neocuproine nearly completely inhibited strand break formation induced by aromatic aldehydes/CuCl2. The prevention of strand breaks induced by aliphatic aldehydes/CuCl2 was less effective. While the inhibition by neocuproine was only 25%, catalase was totally ineffective. In all aldehydes/CuCl2 mixtures the formation of Cu(I) was observed. The results point to different DNA damaging species produced during redox reactions of aromatic and aliphatic aldehydes in combination with CuCl2.
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PMID:DNA single and double strand breaks induced by aliphatic and aromatic aldehydes in combination with copper (II). 873 36

A method for estimating DNA strand breakage and subsequent repair based on alkaline gel electrophoresis was developed and tested with isogenic strains of Escherichia coli deficient in DNA repair enzymes. Samples from a cell suspension were removed at 2 min intervals following a 15 min exposure to 20 mmol l-1 H2O2. Catalase was added and the cells were embedded in blocks of low-melting point agarose and lysed. After alkaline gel electrophoresis, photographs of the gels were taken and the relative lengths of the distributions of DNA fragments were measured with a scanner and computer. The lengths were correlated with survival of the cells exposed to H2O2 and with the importance of particular DNA repair enzymes. Alkaline gel electrophoresis appears to be a relatively simple method for analysing the level of H2O2-caused DNA damage and repair in E. coli.
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PMID:Development of a method based on alkaline gel electrophoresis for estimation of oxidative damage to DNA in Escherichia coli. 876 Mar 22

Catalase is the major peroxisomal H2O2-detoxifying enzyme and is thought to be critical in maintaining low H2O2 levels within a cell. It has been proposed that increased H2O2 levels may be involved in oxidative DNA damage and tumor promotion induced by peroxisome proliferators and other xenobiotics. To develop a mouse model system to address this issue, we have generated transgenic mice that exhibit a three- to four-fold increase in liver catalase levels. The activities of fatty acyl coenzyme A (CoA) oxidase and lauric acid hydroxylase were unchanged in transgenic mice, demonstrating that elevated catalase levels did not alter the activity of these other peroxisome proliferator-induced enzymes that produce active oxygen. These mice should help elucidate the role of H2O2 in cellular events mediated by peroxisome proliferators and other xenobiotics.
DNA Cell Biol 1996 Aug
PMID:Increased liver-specific catalase activity in transgenic mice. 876 64

Pyrroloquinoline quinone (PQQ) plays a role as a vitamin or growth factor. Low concentrations of PQQ induced DNA cleavage sites frequently at thymine and cytosine residues in the presence of NADH and Cu(II). Catalase and bathocuproine inhibited DNA damage, whereas free hydroxyl radical scavengers did not. Electron spin resonance and UV-visible spectrometries showed generation of semiquinone radical and superoxide during the reaction of PQQ with NADH. These results suggest that NADH-dependent PQQ redox cycle generated superoxide and hydrogen peroxide to mediate copper-dependent DNA damage. The present study has proposed a requirement to investigate the potentiality of PQQ carcinogenicity.
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PMID:NADH-mediated DNA damage induced by a new coenzyme, pyrroloquinoline quinone, in the presence of copper(II) ion. 881 12

We have isolated and conducted preliminary characterization of a cell line derived from the Chinese hamster ovary cell line AA8, which we have designated AG8 and which is highly resistant to the cytotoxic effects of H2O2 (approximately 17-fold when the H2O2 treatment was at 37 degrees; approximately 11-fold when the H2O2 treatment was at 4 degrees). AG8 cells were moderately (but significantly; P < 0.05) cross-resistant to CdCl2 (approximately 4-fold), NaAsO2 (approximately 2.3-fold), t-butyl hydroperoxide (approximately 2.9-fold), cumene hydroperoxide (approximately 3-fold), menadione (approximately 1.7-fold) and HgCl2 (approximately 1.5-fold), but were not significantly cross-resistant to hyperthermia (43 degrees), 254 nm UV light, 137Cs gamma-rays, and 42-MeV (p-->Be+) fast neutrons. As regards their biochemical status, AG8 and AA8 cells contain similar non-protein sulfhydryl levels per milligram of protein. Catalase activity (assessed by both spectrophotometry and polarography) was significantly higher in AG8 than in AA8 cells irrespective of whether enzyme activity was expressed per 10(6) cells (approximately 3.6-fold increase) or per milligram of protein (approximately 1.6-fold increase). AG8 cells also exhibited significantly greater glutathione reductase activity than wild-type cells when the data were expressed per 10(6) cells (approximately 2.9-fold) or per milligram of protein (approximately 1.3-fold). Glutathione peroxidase activity was immeasurably low in both cell lines. The susceptibility of the two cell lines to H2O2-mediated generation of DNA single-strand breaks (as measured by alkaline elution) indicated a slightly (approximately 1.5-fold) decreased yield in the resistant AG8 cell line. The two cell lines repaired these breaks with similar kinetics. In contrast, no measurable induction of DNA double-strand breaks (as measured by pulsed-field gel electrophoresis) was apparent in either cell line after survival-curve range concentrations of H2O2. On the basis of these data, it appears that the AG8 phenotype involves two previously identified resistance mechanisms, namely an adaptive component that may or may not involve increased antioxidant capacity, and a second component that does involve increased antioxidant (primarily catalase) capacity.
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PMID:Isolation and preliminary characterization of a Chinese hamster ovary cell line with high-degree resistance to hydrogen peroxide. 886 24

Thymocyte apoptosis is one of the best characterized experimental models of apoptosis that can be induced by a variety of stimuli such as glucocorticoids, ionizing radiation, antibodies, and toxins. Recently, it has been suggested that oxidative stress is a common mediator of apoptosis. However, little is known about the production and possible function of reactive oxygen intermediates (ROI) in thymocytes. We used a highly sensitive flow cytometric assay with the hydrogen peroxide-sensitive dye, 2',7'-dichlorofluorescin diacetate (DCFH-DA), to measure intracellular ROI production in rat thymocytes, to study its primary sources, and to compare ROI levels in normal and apoptotic thymocytes. Apoptosis was induced by incubating the cells in the presence or absence of dexamethasone (Dex) at 37 degrees C in vitro. Normal thymocytes spontaneously produced significant amounts of ROI. Catalase or superoxide dismutase did not affect this intracellular fluorescence, presumably due to their failure to penetrate into the cells. However, N-acetyl-L-cysteine significantly attenuated the fluorescence in a dose-dependent manner. Significant inhibition of the intracellular fluorescence was also observed by addition of N-nitro-L-arginine methyl ester (L-NAME), that could not be reversed by L-arginine. The addition of N-nitro-D-arginine methyl ester (D-NAME) also caused considerable inhibition. This indicates that the inhibition by L-NAME or D-NAME is due to a direct scavenging effect, and nitric oxide production is not likely to be involved. In contrast to neutrophils and macrophages whose superoxide anions are released from membrane-bound NADPH oxidase, the production of ROI in thymocytes is likely to originate mainly from mitochondria, as indicated by the inhibitory effect of the addition of rotenone or antimycin A. The addition of lymphocyte simulators phytohemagglutinin (PHA), concanavalin A (Con A), or phorbol 12-myristate 13-acetate (PMA) enhanced intracellular fluorescence of thymocytes. This increase was abrogated by addition of rotenone or antimycin A. The ROI production was decreased with time after incubation of the thymocytes for 1, 3, and 6 h in vitro. The appearance of apoptosis of thymocytes in vitro, as indicated by DNA content of cells by flow cytometry and DNA ladder formation in agarose gel electrophoresis, was delayed, as compared to the time course of the decreased ROI production. The addition of Dex to the culture medium accelerated both of these processes. The results suggest that a decreased spontaneous production of ROI in thymocytes precedes the spontaneous in vitro apoptosis and Dex exaggerates these changes.
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PMID:Decreased production of reactive oxygen intermediates is an early event during in vitro apoptosis of rat thymocytes. 890 94

Benzene is a widely recognized human carcinogen. The mechanism of DNA damage induced by major benzene metabolites 1,4-benzoquinone (1,4-BQ) and hydroquinone (1,4-HQ) was investigated in relation to apoptosis and carcinogenesis. Pulsed-field gel electrophoresis showed that cellular DNA strand breakage was induced by benzene metabolites. Internucleosomal DNA fragmentation and morphological changes of apoptotic cells were observed at higher concentrations of benzene metabolites. Flow cytometry showed an increase of peroxides in cultured cells treated with benzene metabolites. 1,4-BQ induced these changes at a much lower concentration than 1,4-HQ. Damage to DNA fragments obtained from the c-Ha-ras-1 proto-oncogene was investigated by a DNA sequencing technique. 1,4-BQ + NADH and 1,4-HQ induced piperidine-labile sites frequently at thymine residues in the presence of Cu(II). Catalase and bathocuproine inhibited DNA damage, suggesting that H2O2 reacts with Cu(I) to produce active species causing DNA damage. Electron spin resonance studies showed that semiquinone radical was produced by NADH-mediated reduction of 1,4-BQ and autoxidation of 1,4-HQ, suggesting that benzene metabolites produce O2- and H2O2 via the formation of semiquinone radical. These results suggest that these benzene metabolites cause DNA damage through H2O2 generation in cells, preceding internucleosomal DNA fragmentation leading to apoptosis. The fates of the cells to apoptosis or mutation might be dependent on the intensity of DNA damage and the ability to repair DNA.
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PMID:Oxidative DNA damage and apoptosis induced by benzene metabolites. 891 53

Monoamine oxidases A/B (EC 1.4.3.4, MAO), flavoenzymes located on the outer mitochondrial membrane, catalyze the oxidative deamination of biogenic amines, such as dopamine, serotonin, and norepinephrine. In this study, we examined whether the H2O2 formed during the two-electron oxidation of tyramine [4-(2-aminoethyl)phenol] (a substrate for monoamine oxidases A/B) may contribute to the intramitochondrial steady-state concentration of H2O2 ([H2O2]ss) and, thus, be involved in the oxidative impairment of mitochondrial matrix components. Supplementation of intact, coupled rat brain mitochondria with benzylamine, beta-phenylethylamine, or tyramine showed initial rates of H2O2 production ranging from 0.4- to 1.6 nmol H2O2/min/mg protein. ESR analysis of the oxidative deamination of tyramine by intact rat brain mitochondria revealed the formation of hydroxyl (HO.) and carbon-centered radical adducts--the latter probably originating by the (HO.-)-mediated oxidation of mannitol. The signals were substantially enhanced upon addition of FeSO4 and were abolished by catalase. The intramitochondrial [H2O2]ss calculated in terms of glutathione peroxidase activity during the metabolism of tyramine was 48-fold higher (7.71 +/- 0.25 x 10(-7) M) than that obtained during the oxidation of succinate via complex II in the presence of antimycin A (1.64 +/- 0.2 x 10(-8) M). Oxidative damage to the brain mtDNA was assessed by single strand breakage. The ratio of nicked DNA for the preparations treated with tyramine and those without the amine was 1.5 +/- 0.29 (n = 4), 2.12 +/- 0.28 (n = 8, P < or = 0.05), and 3.12 +/- 0.69 (n = 3, P < or = 0.05) at 15, 30, and 60 min, respectively . Preincubation of mitochondria with tranylcypromine (trans-2-phenylcyclopropylamine), an inhibitor to MAO A/B, abolished mtDNA oxidative damage. Catalase inhibited mtDNA strand breakage by approximately 60%. Incubation of intact, coupled rat brain mitochondria with chlorodinitrobenzene (CDNB) depleted mitochondrial GSH by 72%. Tyramine-dependent damage of mtDNA was decreased by 68% in CDNB-treated mitochondria (with 28% remaining GSH). The [H2O2]ss was slightly increased in CDNB-treated mitochondria: 1.38- and 1.28-fold increase during the oxidation of succinate in the presence of antimycin A and during the oxidation of tyramine, respectively. These results suggest that the H2O2 generated during the MAO-catalyzed oxidation of biogenic amines and possibly certain neurotransmitters at the outer mitochondrial membrane contributes to the intramitochondrial [H2O2]ss and may cause oxidative damage to mtDNA. This is effected by the intramitochondrial concentration of GSH and might have potential implications for aging and neurodegenerative processes.
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PMID:The metabolism of tyramine by monoamine oxidase A/B causes oxidative damage to mitochondrial DNA. 891 26

Reactive oxygen species (ROS) have been shown to impair sperm function. The actions of ROS are reduced by antioxidant enzymes, including catalase. Although catalase-like activity has been demonstrated in semen, there has been no localization or characterization of catalase mRNA expression in the male reproductive tract. Catalase mRNA levels were evaluated by northern blot analysis and in situ hybridization from the male reproductive organs of normal 60-day-old rats, testes of 10- to 90-day-old rats, and testes of rats subjected to efferent duct ligation. Radioactive DNA probes were synthesized using a Klenow polymerase-based specific primer synthetic procedure with a known published sequence for rat catalase. All tissues demonstrated a single transcript of 2.5 kilobases (kb). Low levels of catalase mRNA were detected in the normal testis, epididymis, vas deferens, and prostate. No expression was detectable with northern analysis in seminal vesicle. The levels of catalase mRNA in reproductive organs were compared with the high levels of expression detectable in rat liver. In the testis, catalase expression was primarily localized to peritubular and interstitial cells. In the epididymis and prostate, mRNA was detected in the epithelium. The observed decrease in catalase mRNA levels in the maturing rat testis is consistent with its interstitial localization. The increase in testicular catalase mRNA levels seen in parallel with progressive thinning of the germinal epithelium after efferent duct ligation is also in keeping with a peritubular or interstitial cell localization. The relatively low levels of catalase mRNA expression in the normal adult male reproductive tract undermine the role of catalase as a major antioxidant enzyme in these tissues. The low levels of catalase mRNA in the testis, and the undetectable levels in the seminiferous epithelium, however, imply that the germinal epithelium is predisposed to an oxidative state. These findings may help to explain the known susceptibility of the testis to oxidative stress.
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PMID:Catalase mRNA expression in the male rat reproductive tract. 895 90

Reaction of chromium(VI) with alpha-lipoic acid (reduced form, also called 1,2-dithiolane-3-pentanoic acid) generated Cr(V) and hydroxyl radical (*OH) as measured by electron spin resonance and ESR spin trapping. 5,5-Dimethyl-1-pyrroline was used as a spin trapping agent. Catalase inhibited the *OH generation and enhanced the Cr(V) formation. Superoxide dismutase had an opposite effect. H2O2 enhanced the *OH generation and decreased the Cr(V) formation in a dose-dependent manner. Metal chelators, EDTA, diethylenetriaminepentaacetic acid, deferoxamine, and 1, 10-phenanthroline inhibited *OH radical generation in the order of EDTA > 1,10-phenanthroline > DTPA > deferoxamine. Oxygen consumption measurements indicated that molecular oxygen was used to generate *OH radical in the mixture of Cr(VI) and alpha-lipoic acid. H2O2 and superoxide radical (O2-) were involved as reactive intermediates. The *OH radical was generated via Cr(V)-mediated Fenton-like reaction (Cr(V) + H2O2 --> Cr(VI) + OH- + *OH). HPLC measurements show that the *OH radical generated by this reaction is capable of generating 8-hydroxyl-2'-deoxyguanosine from 2-deoxyguanosine. Incubation of Cr(VI) with cultured Jurkat cells resulted in an activation of DNA binding activity of the nuclear factor (NF)-kappaB. Addition of alpha-lipoic acid enhanced the NF-kappaB activation, while the *OH radical scavenger, sodium formate, inhibited it, showing that alpha-lipoic acid enhanced Cr(VI)-induced NF-kappaB activation via free radical reactions. The results indicate that while alpha-lipoic acid is considered to be an antioxidant, it may be a cellular one-electron Cr(VI) reductant and could be involved in the mechanism of Cr(VI)-induced carcinogenesis.
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PMID:One-electron reduction of chromium(VI) by alpha-lipoic acid and related hydroxyl radical generation, dG hydroxylation and nuclear transcription factor-kappaB activation. 902 68


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