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)

We have previously demonstrated that each region of the ultraviolet (UV) spectrum (UVA, UVB, and UVC) induces the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in purified calf thymus DNA and HeLa cells in a fluence-dependent manner. In the present study, we further characterize the possible reactive oxygen species (ROS) that are involved in the induction of 8-oxodGuo by UV radiation. Sodium azide, a singlet oxygen (1O2) scavenger though its quenching effect on HO. was also reported, inhibited 8-oxodGuo production in calf thymus DNA exposed to UVA, UVB, or UVC in a concentration-dependent fashion with maximal quenching effect of over 90% at a concentration of 10 mM. Catalase, at a concentration of 50 U/ml, reduced the yields of UVA- and UVB-induced 8-oxodGuo formation by approximately 50%, but had little effect on UVC-induced 8-oxodGuo production. In contrast, 50 U/ml of superoxide dismutase (SOD) did not affect induction of 8-oxodGuo by any portion of the UV spectrum. Hydroxyl radical (HO.) scavengers mannitol and dimethylsulfoxide (DMSO) moderately reduced the levels of 8-oxodGuo induced by UVA and UVB, but not those by UVC. Instead, mannitol and DMSO enhanced the formation of 8-oxodGuo induced by UVC. These results suggest that certain types of ROS are involved in UV-induced 8-oxodGuo formation with 1O2 playing the predominant role throughout the UV spectrum. Except for UVC, other ROS such as hydrogen peroxide (H2O2) and HO. may also be involved in UVA- and UVB-induced oxidative DNA damage. Superoxide anion appears not to participate in UV-induced oxidation of guanosine in calf thymus DNA, as SOD did not display any quenching effects.
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PMID:Identification of possible reactive oxygen species involved in ultraviolet radiation-induced oxidative DNA damage. 935 40

Alloxan is known to induce diabetes in experimental animals through destruction of insulin-producing 3-cells of pancreas. The mechanism of DNA damage induced by alloxan was investigated using 32P-labeled human DNA fragments. Cu(II)-dependent DNA damage increased with the concentration of alloxan and NADH. Alloxan induced DNA cleavage frequently at thymine and cytosine residues in the presence of NADH and Cu(II). Catalase and bathocuproine, a Cu(I)-specific chelator, almost completely inhibited DNA damage, suggesting the involvement of H2O2 and Cu(I). Alloxan induced Cu(II)-dependent production of 8-oxodG in calf thymus DNA in the presence of NADH. UV-visible and electron spin resonance (ESR) spectroscopic studies showed that superoxide anion radical and alloxan radical were generated by the reduction of alloxan by NADH, and also by the autoxidation of dialuric acid, the reduced form of alloxan. These results suggest that the copper-oxygen complex derived from the reaction of H2O2 with Cu(I) participates in Cu(II)-dependent DNA damage by alloxan plus NADH and dialuric acid. The mechanism of DNA damage is discussed in relation to diabetogenic action of alloxan.
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PMID:Metal-mediated DNA damage induced by diabetogenic alloxan in the presence of NADH. 974 96

The mechanism of DNA damage induced by metabolites of nitrobenzene was investigated in relation to the carcinogenicity and reproductive toxicity of nitrobenzene. Nitrosobenzene, a nitrobenzene metabolite, induced NADH plus Cu(II)-mediated DNA cleavage frequently at thymine and cytosine residues. Catalase and bathocuproine inhibited the DNA damage, suggesting the involvement of H2O2 and Cu(I). Typical free hydroxyl radical scavengers showed no inhibitory effects on DNA damage. Nitrosobenzene caused the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of NADH and Cu(II). ESR spectroscopic study has confirmed that nitrosobenzene is reduced by NADH to the phenylhydronitroxide radical even in the absence of Cu(II). These results suggest that nitrosobenzene can be reduced non-enzymatically by NADH, and the redox cycle reaction resulted in oxidative DNA damage due to the copper-oxygen complex, derived from the reaction of Cu(I) with H2O2.
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PMID:Oxidative DNA damage by a metabolite of carcinogenic and reproductive toxic nitrobenzene in the presence of NADH and Cu(II). 1019 50

We investigated DNA damage induced by aminoacetone, a metabolite of threonine and glycine. Pulsed-field gel electrophoresis revealed that aminoacetone caused cellular DNA cleavage. Aminoacetone increased the amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in human cultured cells in a dose-dependent manner. The formation of 8-oxodG in calf thymus DNA increased due to aminoacetone only in the presence of Cu(II). DNA ladder formation was observed at higher concentrations of aminoacetone than those causing DNA cleavage. Flow cytometry showed that aminoacetone enhanced the generation of hydrogen peroxide (H2O2) in cultured cells. Aminoacetone caused damage to 32P-5'-end-labeled DNA fragments, obtained from the human c-Ha-ras-1 and p53 genes, at cytosine and thymine residues in the presence of Cu(II). Catalase and bathocuproine inhibited DNA damage, suggesting that H2O2 and Cu(I) were involved. Analysis of the products generated from aminoacetone revealed that aminoacetone underwent Cu(II)-mediated autoxidation in two different pathways: the major pathway in which methylglyoxal and NH+4 are generated and the minor pathway in which 2,5-dimethylpyrazine is formed through condensation of two molecules of aminoacetone. These findings suggest that H2O2 generated by the autoxidation of aminoacetone reacts with Cu(I) to form reactive species capable of causing oxidative DNA damage.
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PMID:Oxidative DNA damage induced by aminoacetone, an amino acid metabolite. 1022 39

To investigate DNA damage induced by Pb2+ and its prevention by scavengers, we determined DNA strand breakage and the formation of 8-hydroxydeoxyguanosine (8-OHdG) in DNA using plasmid relaxation assay and HPLC with electrochemical detection, respectively. Lead acetate induced DNA strand breakage in 10 mM of Hepes buffer, pH 6.8, in a time- and dose-dependent manner. Compared with lead, zinc acetate did not significantly induce DNA breakage. The singlet oxygen scavengers NaN3 and 2,2,6,6-tetramethyl-4-piperidone (TEMP) inhibited lead-induced DNA breakage more efficiently than the hydroxyl radical scavengers mannitol and DMPO. Deuterium oxide (D2O), a singlet oxygen enhancer, potentiated lead-induced DNA breakage. At low ratios to Pb2+, NADPH, glutathione, and 2-mercaptoethanol enhanced lead-induced DNA breakage, whereas high ratios of these agents protected it. Catalase and superoxide dismutase (SOD) did not protect DNA breaks induced by Pb2+. Lead-induced DNA breakage was markedly enhanced by H2O2, and this induction was inhibited by NaN3, TEMP, EDTA, catalase, BSA, and glutathione. In contrast, mannitol and SOD potentiated Pb2+/H2O2-induced DNA breaks. The results indicate that singlet oxygen, lead, and H2O2 are all involved in the reaction system, whereas hydroxyl radical and superoxide did not. Lead could cause a small amount of 8-OHdG formation in calf thymus DNA and dose-dependently induced the formation of this adduct in the presence of H2O2. Singlet oxygen scavengers were more effective than hydroxyl radical scavengers in protection from lead/H2O2-induced 8-OHdG adducts. Taken together, these results suggest that lead may induce DNA damage through a Fenton-like reaction and that singlet oxygen is the principal species involved.
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PMID:Singlet oxygen is the major species participating in the induction of DNA strand breakage and 8-hydroxydeoxyguanosine adduct by lead acetate. 1033 21

Several epidemiological studies and animal experiments showed that 2,4,6-trinitrotoluene (TNT), a commonly used explosive, induced reproductive toxicity. To clarify whether the toxicity results from the interference of endocrine systems or direct damage to reproductive organs, we examined the effects of TNT on the male reproductive system in Fischer 344 rats. TNT administration induced germ cell degeneration, the disappearance of spermatozoa in seminiferous tubules, and a dramatic decrease in the sperm number in both the testis and epididymis. TNT increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in sperm whereas plasma testosterone levels did not decrease. These results suggest that TNT-induced toxicity is derived from direct damage to spermatozoa rather than testosterone-dependent mechanisms. To determine the mechanism of 8-oxodG formation in vivo, we examined DNA damage induced by TNT and its metabolic products in vitro. 4-Hydroxylamino-2,6-dinitrotoluene, a TNT metabolite, induced Cu(II)-mediated damage to 32P-labeled DNA fragments and increased 8-oxodG formation in calf thymus DNA, although TNT itself did not. DNA damage was enhanced by NADH, suggesting that NADH-mediated redox reactions involving TNT metabolites enhanced toxicity. Catalase and bathocuproine inhibited DNA damage, indicating the involvement of H2O2 and Cu(I). These findings suggest that TNT induces reproductive toxicity through oxidative DNA damage mediated by its metabolite. We propose that oxidative DNA damage in the testis plays a role in reproductive toxicity induced by TNT and other nitroaromatic compounds.
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PMID:2,4,6-trinitrotoluene-induced reproductive toxicity via oxidative DNA damage by its metabolite. 1215 May 43

Green tea catechins have antimutagenic and anticarcinogenic activities. On the other hand, several epidemiological studies have indicated significant positive relationship between green tea consumption and cancer. Catechins enhance colon carcinogenesis in rats initiated with chemical carcinogen. To clarify the mechanism underlying the potential carcinogenicity, we investigated the DNA-damaging ability of catechins in human cultured cells. Catechin increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60 but not in HP100, a hydrogen peroxide (H2O2)-resistant cell line derived from HL-60. The catechin-induced formation of 8-oxodG in HL-60 cells significantly decreased by bathocuproine. Furthermore, we investigated DNA damage and its site-specificity induced by catechins, using 32P-labeled DNA fragments. Catechin and epicatechin induced extensive DNA damage in the presence of Cu(II). Catechin caused piperidine-labile sites at thymine and cytosine residues in the presence of Cu(II). Catalase and bathocuproine inhibited the DNA damage, indicating the involvement of H2O2 and Cu(I). NADH enhanced catechins plus Cu(II)-induced 8-oxodG formation in calf thymus DNA, suggesting the redox cycle between catechins and their corresponding quinones, the oxidized forms of catechins. The DNA-damaging ability of epicatechin is stronger than that of catechin, possibly due to the greater turnover frequency of the redox cycle. The difference in their redox properties could be explained by their redox potentials estimated form an ab initio molecular orbital calculation. The present study demonstrated that catechins could induce metal-dependent H2O2 generation during the redox reactions and subsequently damage to cellular and isolated DNA. Therefore, it is reasonably considered that green tea catechins may have the dual function of anticarcinogenic and carcinogenic potentials.
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PMID:Catechins induce oxidative damage to cellular and isolated DNA through the generation of reactive oxygen species. 1456 48

Free radicals are now well known to damage cellular components. To investigate whether age and thyroid level affect peroxidation speed, we examined the levels of malondialdehyde and antioxidant enzyme activities in different age groups of hypothyroid rats. Hypothyroidism was induced in 30- and 60-day-old Wistar Albino rats by the i.p. administration of propylthiouracil (10 mg kg(-1) body weight) for 15 days. While malondialdehyde levels of 30- or 60-day-old hypothyroid rats were increased in liver, they were decreased in the tissues of the heart and thyroid. While glucose-6-phosphate dehydrogenase activity levels did not change in heart, brain and liver tissues of 30-day-old rats, they increased in brain and heart tissues of 60-day-old experimental groups, but decreased in the liver. Catalase activities decreased in the liver and heart of rats with hypothyroidism, but increased in erythrocytes. In control groups while malondialdehyde levels increased in brain, heart and thymus with regard to age, they decreased in plasma. Glucose-6-phosphate dehydrogenase and catalase activities were not affected by age in tissues of the thymus, thyroid and brain, but they were decreased in the heart tissue. The changes in the levels of lipid peroxidation and antioxidant enzyme activities which were determined in different tissues of hypothyroid rats indicate a cause for functional disorder of these tissues. Moreover, there may be changes depending on age at lipid peroxidation and antioxidant enzyme activity levels.
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PMID:Oxidative damage and antioxidant enzyme activities in experimental hypothyroidism. 1462 70

Ethylbenzene is carcinogenic to rats and mice, while it has no mutagenic activity. We have investigated whether ethylbenzene undergoes metabolic activation, leading to DNA damage. Ethylbenzene was metabolized to 1-phenylethanol, acetophenone, 2-ethylphenol and 4-ethylphenol by rat liver microsomes. Furthermore, 2-ethylphenol and 4-ethylphenol were metabolically transformed to ring-dihydroxylated metabolites such as ethylhydroquinone and 4-ethylcatechol, respectively. Experiment with 32P-labeled DNA fragment revealed that both ethylhydroquinone and 4-ethylcatechol caused DNA damage in the presence of Cu(II). These dihydroxylated compounds also induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of Cu(II). Catalase, methional and Cu(I)-specific chelator, bathocuproine, significantly (P<0.05) inhibited oxidative DNA damage, whereas free hydroxyl radical scavenger and superoxide dismutase did not. These results suggest that Cu(I) and H2O2 produced via oxidation of ethylhydroquinone and 4-ethylcatechol are involved in oxidative DNA damage. Addition of an endogenous reductant NADH dramatically enhanced 4-ethylcatechol-induced oxidative DNA damage, whereas ethylhydroquinone-induced DNA damage was slightly enhanced. Enhancing effect of NADH on oxidative DNA damage by 4-ethylcatechol may be explained by assuming that reactive species are generated from the redox cycle. In conclusion, these active dihydroxylated metabolites would be involved in the mechanism of carcinogenesis by ethylbenzene.
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PMID:Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA damage. 1556 Aug 93

It has been demonstrated that administration of high concentrations of monosodium glutamate (MSG), induce oxidative stress in different organs, but not in thymus. In the present study we examined the role of oxidative stress in MSG-induced thymocyte apoptosis. MSG was administrated intraperitoneally (4 mg/g of body weight) for six consecutive days. Animals were sacrificed at 1st, 7th, and 15th day after last MSG dose. MSG administration to animals significantly increased apoptotic rate of thymocytes (P < 0.01), together with significant increase of malondialdehyde (MDA) level (P < 0.001) and xanthine oxidase (XO) activity (P < 0.01), in time dependent manner. Catalase activity, during examination period, was significantly decreased (0 < 0.01). Obtained results showed that MSG treatment induced oxidative stress in thymus, which may have an important role in thymocyte apoptosis induced by MSG.
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PMID:Effect of monosodium glutamate on oxidative stress and apoptosis in rat thymus. 1745 17


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