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

ortho-Phenylphenol (OPP) and its sodium salt, which are used as fungicides and antibacterial agents, have been found to cause carcinomas in the urinary tract of rats. To clarify the carcinogenic mechanism of OPP, we compared the DNA damage inducing ability of an OPP metabolite, phenyl-1,4-benzoquinone (PBQ) with that of another metabolite, phenylhydroquinone (PHQ). Pulsed field gel electrophoresis showed that PBQ and PHQ induced DNA strand breakage in cultured human cells, but PBQ did it more efficiently than PHQ. Significant increases in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) were observed in cells treated with PBQ and PHQ, and the increase of 8-oxodG induced by PBQ was significantly higher than that induced by PHQ. Using 32P-5'-end-labeled DNA fragments obtained from human p53 tumor suppressor gene and c-Ha-ras-1 protooncogene, we showed that PBQ plus NADH, and also PHQ, induced DNA damage frequently at thymine residues, in the presence of Cu(II). The intensity of DNA damage by PBQ was stronger than that by PHQ, showing higher importance of PBQ than other OPP metabolites. Catalase and bathocuproine inhibited Cu(II)-mediated DNA damage by PBQ plus NADH and PHQ, suggesting that H2O2 reacts with Cu(I) to produce active species causing DNA damage. Electron spin resonance and UV-visible spectroscopic studies have demonstrated generation of semiquinone radical and superoxide from the reaction of PBQ with NADH or the Cu(II)-mediated autoxidation of PHQ. The present results suggest that these OPP metabolites cause oxidative DNA damage through H2O2 generation in cells, and the damage may lead to mutation and carcinogenesis. It is concluded that PBQ may play a more important role in the expression of OPP carcinogenicity than other OPP metabolites.
 ...
PMID:Oxidative damage to cellular and isolated DNA by metabolites of a fungicide ortho-phenylphenol. 1033 3

Adduct formation has been considered to be a major causal factor of DNA damage by carcinogenic heterocyclic amines. By means of experiments with 32P-labeled DNA fragments and an electrochemical detector coupled to a high-pressure liquid chromatograph, we investigated whether the N-hydroxy metabolite of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) can cause oxidative DNA damage or not. This metabolite [MeIQx(NHOH)] was found to cause Cu(II)-mediated DNA damage, including 8-oxo-7,8-dihydro-2'-deoxyguanosine formation. When an endogenous reductant, beta-nicotinamide adenine dinucleotide (NADH), was added, the DNA damage was greatly enhanced. Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited the DNA damage, suggesting the involvement of H2O2 and Cu(I). MeIQx(NHOH) frequently induced DNA cleavage at thymine and cytosine residues in the presence of NADH and Cu(II). A UV-visible spectroscopic study showed that little decomposition of MeIQx(NHOH) occurred in the absence of Cu(II), whilst rapid spectral change was observed in the presence of Cu(II), suggesting that Cu(II) catalyzes the autoxidation. The addition of NADH reduced the oxidized product back to MeIQx(NHOH). These results suggest that a copper-peroxo intermediate, derived from the reaction of Cu(I) with H2O2, participates in Cu(II)-dependent DNA damage by MeIQx(NHOH), and NADH enhances the DNA damage via a redox cycle. We conclude that in addition to DNA adduct formation, oxidative DNA damage plays an important role in the carcinogenic process of MeIQx.
 ...
PMID:Mechanism of oxidative DNA damage induced by a heterocyclic amine, 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline. 1035 40

Nitro derivative (nitro-IQ) of a carcinogenic heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is known to be a potent mutagen as well as IQ, and nitro-IQ is believed to be activated enzymatically by nitroreductase. We investigated nonenzymatic reduction of nitro-IQ by an endogenous reductant NADH and the ability of inducing DNA damage by nitro-IQ. Nitro-IQ caused DNA damage including 8-oxo-7,8-dihydro-2'-deoxyguanosine in the presence of NADH and Cu(II). Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited the DNA damage, suggesting the involvement of H2O2 and Cu(I). Nitro-IQ induced DNA cleavage frequently at thymine and cytosine residues in the presence of NADH and Cu(II). UV-vis spectroscopic study showed that no spectral change of Nitro-IQ and NADH was observed in the absence of Cu(II), while rapid spectral change was observed in the presence of Cu(II), suggesting that Cu(II) mediated redox reaction of nitro-IQ and NADH. These results suggest that nitro-IQ can be reduced nonenzymatically by NADH in the presence of Cu(II), and the redox reaction resulted in oxidative DNA damage due to the copper-oxygen complex, derived from the reaction of Cu(I) with H2O2. We conclude that nonenzymatic reduction of nitro-IQ and resulting in oxidative DNA damage can play a role in carcinogenesis of IQ.
 ...
PMID:Nonenzymatic reduction of nitro derivative of a heterocyclic amine IQ by NADH and Cu(II) leads to oxidative DNA damage. 1038 1

Dihydrolipoamide dehydrogenase (LADH) from Trypanosoma cruzi was inactivated by treatment with myeloperoxidase (MPO)-dependent systems. With MPO/H2O2/NaCl, LADH lipoamide reductase and diaphorase activities significantly decreased as a function of incubation time. Iodide, bromide, thiocyanide and chloride effectively supplemented the MPO/H2O2 system, KI and NaCl being the most and the least effective supplements, respectively. LADH inactivation by MPO/H2O2/NaCl and by NaOCl was similarly prevented by thiol compounds such as GSH, L-cysteine, N-acetylcysteine, penicillamine and N-(2-mercaptopropionyl-glycine) in agreement with the role of HOCI in LADH inactivation by MPO/H2O2/NaCl. LADH was also inactivated by MPO/NADH/halide, MPO/H2O2/NaNO2 and MPO/NADH/NaNO2 systems. Catalase prevented the action of the NADH-dependent systems, thus supporting H2O2 production by NADH-supplemented LADH. MPO inhibitors (4-aminobenzoic acid hydrazide, and isoniazid), GSH, L-cysteine, L-methionine and L-tryptophan prevented LADH inactivation by MPO/H2O2/NaNO2. Other MPO systems inactivating LADH were (a) MPO/H2O2/chlorpromazine; (b) MPO/H2O2/monophenolic systems, including L-tyrosine, serotonin and acetaminophen and (c) MPO/H2O2/di- and polyphenolic systems, including norepinephrine, catechol, nordihydroguaiaretic acid, caffeic acid, quercetin and catechin. Comparison of the above effects and those previously reported with pig myocardial LADH indicates that both enzymes were similarly affected by the MPO-dependent systems, allowance being made for T. cruzi LADH diaphorase inactivation and the greater sensitivity of its LADH lipoamide reductase activity towards the MPO/H2O2/NaCl system and NaOCl.
 ...
PMID:Trypanosoma cruzi dihydrolipoamide dehydrogenase is inactivated by myeloperoxidase-generated "reactive species". 1082 17

Dihydrolipoamide dehydrogenase (LADH) from Trypanosoma cruzi, the causative agent of Chagas' disease, was inactivated by treatment with myeloperoxidase (MPO)-dependent systems. LADH lipoamide reductase and diaphorase activities decreased as a function of incubation time and composition of the MPO/H2O2/halide system, a transient increase preceding the loss of diaphorase activity. Iodide, bromide, thiocyanide and chloride were effective components of MPO/H2O2 or MPO/NADH systems. Catalase prevented LADH inactivation by the MPO/NADH/halide systems in agreement with H2O2 production by NADH-supplemented LADH. Thiol compounds (L-cysteine, N-acetylcysteine, penicillamine, N-(2-mercaptopropionylglycine) and Captopril prevented LADH inactivation by the MPO/H2O2/NaCl system and by NaOCl, thus supporting HOCl as agent of the MPO/H2O2/NaCl system. MPO/H2O2/NaNO2 and MPO/NADH/NaNO2 inactivated LADH, the reaction being prevented by MPO inhibitors and thiol compounds. T. cruzi LADH was affected by MPO-dependent systems like myocardial LADH, allowance being made for the variation of the diaphorase activity and the greater sensitivity of the T. cruzi enzyme to MPO/H2O2/halide systems.
 ...
PMID:Inactivation of Trypanosoma cruzi dihydrolipoamide dehydrogenase by leukocyte myeloperoxidase systems: role of hypochloride and nitrite related radicals. 1100 5

Nitropyrenes are carcinogenic pollutants. Adduct formation following nitro-reduction is considered to be a major cause of nitropyrene-mediated DNA damage. We investigated the role of 1-nitrosopyrene, a metabolite of 1-nitropyrene, in causing oxidative DNA damage, using 32P-5'-end-labeled DNA. 1-Nitrosopyrene was found to facilitate Cu(II)-mediated DNA damage in the presence of NADH. Catalase and a Cu(I)-specific chelator attenuated DNA damage, indicating the involvement of H2O2 and Cu(I). Typical *OH scavenger did not have a significant effect. These results suggest that the main reactive species is probably a DNA-copper-hydroperoxo complex. We also measured 8-oxo-7,8-dihydro-2'-deoxyguanosine formation by 1-nitrosopyrene in the presence of Cu(II) and NADH, using an electrochemical detector coupled to a high-pressure liquid chromatograph. We conclude that oxidative DNA damage, in addition to DNA adduct formation, may play an important role in the carcinogenesis of nitropyrenes.
 ...
PMID:Oxidative DNA damage by a metabolite of carcinogenic 1-nitropyrene. 1116 76

Formation of adducts has been considered to be a major causal factor of DNA damage by carcinogenic aminoazo dyes. We investigated whether a metabolite of hepatocarcinogenic 4-dimethylaminoazobenzene (DAB) can cause oxidative DNA damage or not, using (32)P-5'-end-labeled DNA fragments. The DAB metabolite N-hydroxy-4-aminoazobenzene (N-OH-AAB) was found to cause Cu(II)-mediated DNA damage, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation. When an endogenous reductant, beta-nicotinamide adenine dinucleotide (NADH) was added, the DNA damage was greatly enhanced. Very low concentrations of N-OH-AAB could induce DNA damage via redox reactions. Catalase and a Cu(I)-specific chelator inhibited the DNA damage, suggesting the involvement of H2O2 and Cu(I). A typical.OH scavenger did not inhibit the DNA damage. The main reactive species are probably DNA-copper-hydroperoxo complexes. We conclude that oxidative DNA damage may play an important role in the carcinogenic processes of DAB, in addition to DNA adduct formation.
 ...
PMID:Oxidative DNA damage induced by an N-hydroxy metabolite of carcinogenic 4-dimethylaminoazobenzene. 1117 40

DNA adduct formation is thought to be a major cause of DNA damage by carcinogenic aromatic amines. We investigated the ability of an aromatic amine, 4-aminobiphenyl (4-ABP) and its N-hydroxy metabolite (4-ABP(NHOH)) to cause oxidative DNA damage, using (32)P-labeled human DNA fragments from the p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. 4-ABP(NHOH) was found to cause Cu(II)-mediated DNA damage, especially at thymine residues. Addition of the endogenous reductant NADH led to dramatic enhancement of this process. Catalase and bathocuproine, a Cu(I)-specific chelator, reduced the amount of DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). 4-ABP(NHOH) dose-dependently induced 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in the presence of Cu(ll) and NADH. 4-ABP(NHOH) conversion to nitrosobiphenyl, as measured by UV-visible spectroscopy, occurred rapidly in the presence of Cu(II), suggesting Cu(II)-mediated autoxidation. Increased amounts of 8-OHdG were found in HL-60 cells compared to the H(2)O(2)-resistant clone HP100 following 4-ABP(NHOH) treatment, further supporting the involvement of H(2)O(2). The present study demonstrates that an N-hydroxy derivative of 4-ABP induces oxidative DNA damage through H(2)O(2) in both a cell-free system and in cultured human cells. We conclude that, in addition to DNA adduct formation, oxidative DNA damage may play an important role in the carcinogenic process of 4-ABP.
 ...
PMID:Mechanism of oxidative DNA damage induced by carcinogenic 4-aminobiphenyl. 1127 76

Estrogen-induced carcinogenesis involves enhanced cell proliferation (promotion) and genotoxic effects (initiation). To investigate the contribution of estrogens and their metabolites to tumor initiation, we examined DNA damage induced by estradiol and its metabolites, the catechol estrogens 2-hydroxyestradiol (2-OHE(2)) and 4-hydroxyestradiol (4-OHE(2)). In the presence of Cu(II), catechol estrogens formed piperidine-labile sites at thymine and cytosine residues in (32)P 5'-end-labeled DNA fragments and induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine. NADH markedly enhanced Cu(II)-dependent DNA damage mediated by nanomolar concentrations of catechol estrogens. Catalase and bathocuproine inhibited the DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). These results suggest that H(2)O(2), generated during Cu(II)-catalyzed autoxidation of catechol estrogens, reacts with Cu(I) to form the Cu(I)-peroxide complex, leading to oxidative DNA damage, and that NADH enhanced DNA damage through the formation of redox cycle. To investigate the role of estrogens and their metabolites in tumor promotion, we examined their effects on proliferation of estrogen-dependent MCF-7 cells. Estradiol enhanced the proliferation of MCF-7 cells at much lower concentrations than catechol estrogens. These findings indicate that catechol estrogens play a role in tumor initiation through oxidative DNA damage, whereas estrogens themselves induce tumor promotion and/or progression by enhancing cell proliferation in estrogen-induced carcinogenesis.
 ...
PMID:Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation. 1129 Oct 67

Norharman (9H-pyrido[3,4-b]indole), which is a heterocyclic amine included in cigarette smoke or cooked foodstuffs, is not mutagenic itself. However, norharman reacts with non-mutagenic aniline to form mutagenic aminophenylnorharman (APNH), of which DNA adducts formation and hepatocarcinogenic potential are pointed out. We investigated whether N-OH-APNH, an N-hydroxy metabolite of APNH, can cause oxidative DNA damage or not, using 32P-labeled DNA fragments. N-OH-APNH caused Cu(II)-mediated DNA damage. When an endogenous reductant, beta-nicotinamide adenine dinucleotide (NADH) was added, the DNA damage was greatly enhanced. Catalase and a Cu(I)-specific chelator inhibited DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). Typical -*OH scavenger did not inhibit DNA damage. These results suggest that the main reactive species are probably copper-hydroperoxo complexes with DNA. We also measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation by N-OH-APNH in the presence of Cu(II), using an electrochemical detector coupled to a high-pressure liquid chromatograph. Addition of NADH greatly enhanced 8-oxodG formation. UV-VIS spectra and mass spectra suggested that N-OH-APNH was autoxidized to nitrosophenylnorharman (NO-PNH). We speculated that NO-PNH was reduced by NADH. Cu(II) facilitated the redox cycle. In the presence of NADH and Cu(II), very low concentrations of N-OH-APNH could induce DNA damage via redox reactions. We conclude that oxidative DNA damage, in addition to DNA adduct formation, may play an important role in the expression of genotoxicity of APNH.
 ...
PMID:Oxidative DNA damage by an N-hydroxy metabolite of the mutagenic compound formed from norharman and aniline. 1142 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>