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)

Reactive oxygen intermediates play a role in chronic renal injury and glomerulosclerosis. We investigate changes in renal cortex antioxidant enzyme gene expression in the rat remnant-kidney model of chronic renal failure and compare the new data to enzyme activities published earlier. Antioxidant enzyme gene expression is evaluated by Northern blot analysis of cortex mRNA, using cDNA probes for catalase, copper/zinc-containing superoxide dismutase, and glutathione peroxidase. Catalase gene expression decreases during development of renal failure; this decrease is accompanied by decreased catalase activity during the glomerulosclerosis phase of the remnant-kidney model. Copper/zinc superoxide dismutase and glutathione peroxidase gene expression remain at a normal level during progression of the model, whereas their activities show a temporary decrease in the early remnant kidney. In the remnant-kidney model, catalase seems to be more vulnerable to reactive oxygen intermediates than superoxide dismutase and glutathione peroxidase. Our results show that antioxidant enzyme activity and gene expression do not change in the same direction at all times during disease development and that all antioxidant enzymes do not respond in the same way.
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PMID:Antioxidant enzyme gene expression in rats with remnant kidney induced chronic renal failure. 1072 48

Several isothiocyanates have been proposed as promising chemopreventive agents for human cancers. However, it has been reported that allyl isothiocyanate exhibit carcinogenic potential, and benzyl isothiocyanate and phenethyl isothiocyanate have tumor-promoting activities. We investigated whether these isothiocyanates could cause DNA damage, using (32)P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. Allyl isothiocyanate caused Cu(II)-mediated DNA damage and formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) more strongly than benzyl and phenethyl isothiocyanates. Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited Cu(II)-mediated DNA damage by these isothiocyanates, suggesting involvement of H(2)O(2) and Cu(I). Isothiocyanates induced DNA damage frequently at thymine and cytosine residues in the presence of Cu(II). A UV-visible spectroscopic study revealed an association between the generation of superoxide and the yield of SH group from isothiocyanates. Furthermore, the yield of 8-oxodG formation was correlated with their superoxide-generating ability. Allyl isothiocyanate significantly induced 8-oxodG formation in HL-60 cells, but not in H(2)O(2)-resistant HP100 cells, suggesting the involvement of H(2)O(2) in cellular DNA damage. We conclude that oxidative DNA damage may play important roles in carcinogenic processes induced by allyl isothiocyanate.
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PMID:Mechanism of oxidative DNA damage induced by carcinogenic allyl isothiocyanate. 1075 76

Hydrazobenzene is carcinogenic to rats and mice and azobenzene is carcinogenic to rats. Hydrazobenzene is a metabolic intermediate of azobenzene. To clarify the mechanism of carcinogenesis by azobenzene and hydrazobenzene, we investigated DNA damage induced by hydrazobenzene, using 32P-5'-end-labeled DNA fragments obtained from the c-Ha-ras-1 protooncogene and the p53 tumor suppressor gene. Hydrazobenzene caused DNA damage in the presence of Cu(II). Piperidine treatment enhanced the DNA damage greatly, suggesting that hydrazobenzene caused base modification and liberation. However, azobenzene did not cause DNA damage even in the presence of Cu(II). Hydrazobenzene plus Cu(II) caused DNA damage frequently at thymine residues. Catalase and a Cu(I)-specific chelator inhibited Cu(II)-mediated DNA damage by hydrazobenzene. Typical *OH scavengers did not inhibit the DNA damage. The main active species is probably a metal oxygen complex, such as Cu(I)-OOH. Formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine was increased by hydrazobenzene in the presence of Cu(II). Oxygen consumption and UV-Visible spectroscopic measurements have shown that hydrazobenzene is autoxidized to azobenzene with H2O2 formation. It is considered that the metal-mediated DNA damage by hydrazobenzene through H2O2 generation may be relevant for the expression of carcinogenicity of azobenzene and hydrazobenzene.
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PMID:Copper-dependent DNA damage induced by hydrazobenzene, an azobenzene metabolite. 1079 12

Oxidation by copper/quinone-containing serum amine oxidases (SAO) is a well-known cause of polyamine cytotoxicity. Spermine oxidation exerts potent immunosuppressive effects in animal cells, but the cell death mechanism involved remains unclear. We compared biochemical and morphological parameters of SAO-mediated cell death in L1210 mouse leukemia cells with normal or amplified ornithine decarboxylase gene expression with those observed during apoptosis induced by deregulated polyamine uptake or by okadaic acid. None of the characteristic features of apoptotic cell death (e.g., chromatin condensation, nuclear fragmentation, internucleosomal DNA cleavage, poly(ADP-ribose) polymerase cleavage) were observed during spermine oxidation-mediated cell death, which was clearly necrotic by morphological criteria. Inhibition of a wide spectrum of caspases did not prevent SAO-dependent cell death, whereas N-acetylcysteine completely abolished the cytotoxic effects of spermine oxidation. Catalase only delayed spermine oxidation-induced cell death without affecting its modality or preventing depletion of intracellular glutathione, suggesting that both H(2)O(2) and aminoaldehydes generated by SAO-mediated spermine oxidation contribute to SAO-induced necrosis. Interestingly, redistribution of phosphatidylserine to the outer leaflet of the plasma membrane, usually a diagnostic feature of apoptosis, preceded necrotic cytolysis triggered by spermine oxidation. Thus, L1210 cell death caused by SAO-mediated spermine oxidation has all the attributes of primary necrosis, but is also accompanied by loss of phospholipid asymmetry, indicating that the latter phenomenon may not be unique to apoptosis. Phosphatidylserine exposure, a potent engulfment signal for phagocytes, might contribute to the immunosuppressive effects of plasma polyamines through a controlled and rapid necrotic process involving SAO.
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PMID:Spermine oxidation leads to necrosis with plasma membrane phosphatidylserine redistribution in mouse leukemia cells. 1094 76

We have investigated oxidative modification of human Cu, Zn-superoxide dismutase (SOD) by alkylperoxyl radicals and alkylperoxides. To generate free radicals, we used the hydrophilic azocompound, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). When Cu,Zn-SOD was incubated with AAPH, the enzyme activity was decreased gradually in a time-dependent manner. The oxidative damage to Cu,Zn-SOD by AAPH-derived radicals led to protein fragmentation which is associated with the inactivation of enzyme. Incubation with AAPH resulted in the release of copper ions from Cu,Zn-SOD and the generation of protein carbonyl derivatives. Catalase did not protect the fragmentation of Cu,Zn-SOD whereas azide, glutathione and a metal chelator, diethylenetriamine pentaacetic acid inhibited the protein fragmentation. When Cu,Zn-SOD that has been exposed to AAPH was subsequently analyzed by amino acid analysis, lysine, histidine, proline, and valine residues were particularly sensitive. It is suggested that oxidative damage of Cu,Zn-SOD by AAPH-derived radicals may induce the perturbation of cellular antioxidant defense systems and subsequently lead to the deleterious condition in cells.
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PMID:Oxidative modification and inactivation of Cu,Zn-superoxide dismutase by 2,2'-azobis(2-amidinopropane) dihydrochloride. 1108 42

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.
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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.
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PMID:Oxidative DNA damage induced by an N-hydroxy metabolite of carcinogenic 4-dimethylaminoazobenzene. 1117 40

The effect of two naturally occurring thiols, such as cysteine and homocysteine, has been examined for their ability to induce deoxyribose degradation and DNA damage. Copper(II) ions have been added to incubation mixtures and oxygen consumption measurements have been performed in order to correlate the observed damaging effects with the rate of metal catalyzed thiol oxidation. Ascorbic acid plus copper has been used as a positive control of deoxyribose and DNA oxidation due to reactive oxygen species. Cysteine or homocysteine in the presence of copper ions induce the degradation of deoxyribose and the yield of 8-hydroxy-2'-deoxyguanosine (8-OHdG), although important differences are observed between the two thiols tested, homocysteine being less reactive than cysteine. DNA cleavage is induced by cysteine in the presence of copper(II) ions but not by homocysteine. Catalase and thiourea, but not superoxide dismutase (SOD), were shown to inhibit the damaging effects of cysteine on deoxyribose or DNA suggesting that H(2)O(2) and *OH radicals are responsible for the observed induced damage. The results indicate that there are differences between the damaging effects of the two thiols tested towards deoxyribose and DNA damage. The pathophysiological importance will be discussed.
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PMID:Differences between cysteine and homocysteine in the induction of deoxyribose degradation and DNA damage. 1118 90

We investigated survival of two kinds of human embryonic cells (CLV102, Lu106) and human melanoma cells (Mel8) exposed to exogenous iron and copper ions in the absence or in the presence of ascorbic acid, catalase and superoxide dismutase. Iron ions produced cytotoxicity towards both kinds of cells dependent on its concentration. Catalase suppressed the cytotoxicity induced by iron ions in Lu106 cells. whereas in CLV102 and Mel8 cells, was ineffective. By contrast, superoxide dismutase abolished the cytotoxicity of iron ions towards CLV102 cells, whereas in Lu106 and Mel8 cells, was ineffective. The mixture of iron ions with ascorbic acid was less cytotoxic than iron ions themselves or ascorbic acid itself, only in CLV102 and Lu106 cells. Ascorbic acid enhanced drastically cytotoxic effect of copper ions in all kinds of cells.
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PMID:Influence of ascorbic acid on cytotoxic activity of copper and iron ions in vitro. 1124 46

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.
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PMID:Mechanism of oxidative DNA damage induced by carcinogenic 4-aminobiphenyl. 1127 76


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