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)

Investigations were conducted on the distribution of rat liver catalase subsequent to electrofocusing in a pH gradient. Differences were observed depending on the enzyme being extracted from the total mitochondrial fraction, from the supernatant of the homogenate or from purified peroxisomes. Catalase solubilized from the total mitochondrial fraction exhibits an apparent isoelectric point lower than that of catalase derived from the supernatant. Catalase released from purified peroxisomes shows a behavior similar to that of the supernatant catalase. It has been concluded that, in a total mitochondrial fraction, a factor is present that alters the electric charge of the catalase molecule during or after the extraction of the enzyme. This factor is probably associated with lysosomes existing together with peroxisomes and mitochondria in a total mitochondrial fraction. As a matter of fact, the addition of an extract of purified lysosomes to purified peroxisomes or to supernatant will cause a shift towards a more acid pH of catalase distribution subsequent to electrofocalization.
Cancer Biochem Biophys 1976
PMID:Behavior of rat liver catalase during electrophoresis in a pH gradient. 101 40

The effects of catalase, superoxide dismutase, mannitol, glutathione, and diallyl sulfide on quercetin-induced DNA damage and lipid peroxidation were investigated in a model system of isolated rat-liver nuclei under aerobic conditions and in the presence of equimolar iron or copper. Mannitol produced a small but significant inhibition of the concurrent nuclear DNA damage and lipid peroxidation induced by quercetin in the presence of iron or copper. Catalase significantly decreased quercetin-induced nuclear DNA damage only in the presence of iron and had no significant effect on lipid peroxidation. Superoxide dismutase showed no significant effect on nuclear DNA damage, but stimulated the quercetin-induced lipid peroxidation only in the presence of copper. Glutathione significantly inhibited the nuclear lipid peroxidation but enhanced the DNA damage. Diallyl sulfide significantly enhanced the nuclear DNA damage but stimulated the lipid peroxidation only in the presence of iron. These results suggest that the reactive oxygen species, especially the hydroxyl radicals, are responsible for the concurrent lipid peroxidation and DNA damage induced by quercetin in the presence of iron or copper in isolated rat-liver nuclei.
Cancer Lett 1991 Dec 01
PMID:Effects of antioxidants on quercetin-induced nuclear DNA damage and lipid peroxidation. 175 17

Hydralazine caused site-specific DNA damage in the presence of Cu(II), Co(II), Fe(III), or peroxidase/H2O2. The order of inducing effect of metal ions on hydralazine-dependent DNA damage [Cu(II) greater than Co(II) greater than Fe(III)] was related to that of accelerating effect on the O2 consumption rate of hydralazine autoxidation. Catalase completely inhibited DNA damage by hydralazine plus Cu(II), but hydroxyl radical (.OH) scavengers and superoxide dismutase did not. On the other hand, DNA damage by hydralazine plus Fe(III) was inhibited by catalase and .OH scavengers. Hydralazine plus Cu(II) induced piperidine-labile sites predominantly at guanine and some adenine residues, whereas hydralazine plus Fe(III) caused cleavages at every nucleotide. Activation of hydralazine by peroxidase/H2O2 caused guanine-specific modification in DNA. ESR-spin trapping experiment showed that .OH and superoxide are generated during the Fe(III)- or Cu(II)-catalysed autoxidation of hydralazine, respectively, and that nitrogen-centered radical is generated during the Cu(II)- or peroxidase-catalysed oxidation. The generation of nitrogen-centered radical was also supported by HPLC-mass spectrometry. The results suggest that the guanine-specific modification by the enzymatic activation of hydralazine is due to the nitrogen-centered hydralazyl radical or derived active species, whereas .OH participates in DNA damage by hydralazine plus Fe(III). The mechanism of hydralazine plus Cu(II)-induced DNA damage is complex. The possible role of the DNA damage induced by hydralazine in the presence of Cu(II) or peroxidase/H2O2 is discussed in relation to hydralazine-induced lupus, mutation, and cancer.
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PMID:Free radical production and site-specific DNA damage induced by hydralazine in the presence of metal ions or peroxidase/hydrogen peroxide. 184 78

Mechanisms for resistance were studied in three classic type, human small cell lung cancer cell lines, GLC14, GLC16, and GLC19, that were established from one patient during clinical follow-up. Clinically the tumor changed from sensitive (GLC14) to completely resistant to (chemo)therapy (GLC19) during this period. The stain with JSB-1 antibody, detecting the Mr 170,000 multidrug resistance associated glycoprotein, was most pronounced in GLC16 and absent in GLC19. Intracellular Adriamycin (Adr) concentrations were decreased in GLC16 and GLC19 versus GLC14. Glutathione levels were 12.9, 15.5, and 16.6 micrograms/mg protein; total sulfhydryl groups were 36.5, 45.7, and 48.8 micrograms/mg protein; and glutathione S-transferase activity was 13, 29, and 43 nmol I-chloro-2,4-dinitrobenzene/min/mg protein for GLC14, GLC16, and GLC19, respectively. Incubation with DL-buthionine-S,R-sulfoximine increased Adr and cisplatin induced cytotoxicity, whereas X-ray induced cytotoxicity remained the same. Catalase activity increased from 0.88 to 1.73 to 3.83 mumol H2O2/min/mg protein in, respectively, GLC14, GLC16, and GLC19. Compared to GLC14 and GLC16, Adr induced a higher amount of DNA strand breaks in GLC19. In none of the three cell lines could Adr induced DNA strand breaks be repaired. X-ray induced a comparable amount of DNA strand breaks in all three cell lines but all cell lines were capable of repairing the X-ray induced DNA strand breaks within 90 min. It is concluded that a number of different mechanisms are operative and that some but not all of the observed changes in mechanisms for drug resistance in these lines correlate with the clinical data.
Cancer Res 1989 Aug 01
PMID:Resistance mechanisms in three human small cell lung cancer cell lines established from one patient during clinical follow-up. 254 37

The passage of circulating tumor cells across vessel walls is an important step in cancer metastasis and is promoted by endothelial injury. Because Walker carcinosarcoma 256 (W256) cells generate oxygen-derived free radicals after cellular activation, the authors tested the hypothesis that these cancer cells can damage endothelial monolayers by producing such reactive oxygen species. To confirm that oxygen-derived radicals can damage endothelial cells, 3H-2-deoxyglucose-labeled human endothelial cell monolayers were exposed to xanthine oxidase in the presence of 0.2 mmol/l xanthine. 3H-2-deoxyglucose release was observed after the addition of xanthine oxidase in concentrations ranging from 6.5 x 10(-3) to 52 x 10(-3) units/ml. The extent of damage correlated with xanthine oxidase-dependent chemiluminescence (r = 0.91). Chemiluminescence assays in the presence of 5 x 10(-5) M luminol confirmed activation of the W256 cells by 1 x 10(-6) M chemotactic peptide fMLP. When fMLP-activated activated W256 cells were incubated with endothelial monolayers, concentrations of 2 x 10(6) to 6 x 10(6) W256 cells/ml were found to cause a 27% increase in the specific release of 2-deoxyglucose after a 90-minute incubation. A small but significant increase in 3H-2-deoxyglucose release also was observed in the absence of fMLP. Detection of 3H-2-deoxyglucose release in the presence of activated or unactivated tumor cells was dependent on preincubating the endothelial cell monolayer with 1 mM buthionine sulfoximine, an inhibitor of glutathione synthesis. Under these conditions, the specific release of 3H-2-deoxyglucose was increased from nondetectable levels to 21%, in the presence of 6.5 x 10(-3) units of the oxidase. Cultured W256 cells promoted isotope release from endothelial cell monolayers when activated with phorbol myristate acetate. Catalase (1000 units/ml) inhibited the tumor cell-induced release of 3H-2-deoxyglucose by 84% whereas superoxide dismutase, even at concentrations of 1 mg/ml, had no effect. A requirement for cell contact was shown because addition of cell-free supernatants from fMLP activated tumor cells did not cause 3H-2-deoxyglucose release and because pretreatment of W256 cells with 1 microM cytochalasin B inhibited their ability to promote isotope release even while increasing tumor cell-generated chemiluminescence threefold. Electron microscopy revealed that fewer cytochalasin B-treated W256 cells were attached to the endothelial cell monolayer than in untreated controls. It is concluded that the W256 tumor cells can damage endothelial cells directly via a mechanism involving production of reactive oxygen species.
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PMID:Walker carcinosarcoma cells damage endothelial cells by the generation of reactive oxygen species. 270 6

Photoradiation therapy with porphyrins and light offers an alternative approach to the management of certain types of cancer. The mechanism of tissue destruction mediated by this modality is poorly understood. In this study, epidermal microsomes incubated in vitro with Photofrin-I (Pf-I) and Photofrin-II (Pf-II) followed by exposure to radiation (approximately 400 nm) resulted in increased (180%) NADPH-supported (enzymatic) as well as ADP/iron-supported (140%) (nonenzymatic) lipid peroxidative damage as measured by malondialdehyde formation. Lipid peroxidation by Pf-I and Pf-II was found to be differentially affected by quenchers of singlet oxygen (2,5-dimethylfuran, histidine, beta-carotene, ascorbic acid, and sodium azide), superoxide anion (superoxide dismutase), and the hydroxyl radical (sodium benzoate, mannitol, and ethanol). Catalase, a quencher of hydrogen peroxide, afforded significant protection only against Pf-II-enhanced lipid peroxidative damage while it had little effect against the Pf-I-mediated reaction. Deuterium oxide, which is known to increase the half-life of singlet oxygen, was found to enhance Pf-I-mediated lipid peroxidation but produced insignificant effects upon Pf-II-mediated photosensitization. Our results indicate that Pf-I and Pf-II, which are employed for the photodynamic therapy of malignant tumors, evoke membrane damage by generating different reactive oxygen species. The Pf-I-mediated photodestruction mainly involves a type II mechanism via singlet oxygen formation, whereas Pf-II-mediated photodestruction preferentially involves a type I mechanism by generating superoxide anions and hydroxyl radicals. Our data indicate that tumor necrosis evoked by porphyrins and light is likely due to the generation of reactive oxygen species.
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PMID:Differential role of reactive oxygen intermediates in photofrin-I- and photofrin-II-mediated photoenhancement of lipid peroxidation in epidermal microsomal membranes. 283 56

Reactivities of benzene metabolites (phenol, catechol, hydroquinone, 1,4-benzoquinone, 1,2,4-benzenetriol) and related polyphenols (resorcinol, pyrogallol, phloroglucinol) with DNA were investigated by a DNA sequencing technique using 32P 5'-end-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene, and the reaction mechanism was studied by UV-visible and electron-spin resonance spectroscopies. 1,2,4-Benzenetriol caused strong DNA damage even without alkali treatment. Alkali-labile sites induced by 1,2,4-benzenetriol were base residues of guanine and adjacent thymine. Catalase, superoxide dismutase and methional inhibited the DNA damage completely, but sodium formate did not inhibit it. 1,2,4-Benzenetriol-induced DNA damage was inhibited by the addition of a Cu(I)-specific chelating agent, bathocuproine, and was accelerated by the addition of Cu(II). The addition of Fe(III) did not create any significant effects on 1,2,4-benzenetriol-induced DNA damage. Electron-spin resonance studies using spin traps demonstrated that addition of Fe(III) increased hydroxyl radical production during the autoxidation of 1,2,4-benzenetriol, whereas the addition of Cu(II) did not. The results suggest that DNA damage was caused by an unidentified active species which was produced by the autoxidation of 1,2,4-benzenetriol in the presence of Cu(II), rather than by hydroxyl radicals. The possibility that 1,2,4-benzenetriol-induced DNA damage is one of the primary reactions in carcinogenesis induced by benzene is discussed.
Cancer Res 1989 Jan 01
PMID:Human DNA damage induced by 1,2,4-benzenetriol, a benzene metabolite. 290 43

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is a stimulator of chemiluminescence (CL) in SENCAR mouse epidermal cells. The CL response is TPA dose dependent (8 to 800 nM) as well as proportional to the number of cells used. Treatment with 166 nM TPA results in a CL response that peaks by 15 min although a strong response persists for over 30 min. The CL response can be inhibited by superoxide dismutase and the superoxide dismutase mimetic copper(II) (3,4 diisopropylsalicylic acid)2, suggesting that the CL response may be due to or mediated by superoxide anions. Catalase, which is specific for H2O2, and mannitol, which is a scavenger for hydroxyl radicals, had negligible inhibitory effects. The CL response is also inhibited by retinoic acid and the analogue ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8- nonatetraenoate. A series of phorbol esters with different promoting abilities produced corresponding CL responses. The second stage tumor promoter mezerein is as effective as TPA in stimulating CL. Inhibitors of various parts of the arachidonic acid cascade were found to affect the TPA-induced CL response in a manner that corresponds to their effects in vivo tumor promotion experiments: agents which are predominantly lipoxygenase inhibitors, i.e., nordihydroguaiaretic acid, benoxaprofen, or agents which are effective against both lipoxygenase or cyclooxygenase, i.e., 5,8,11,14-eicosatetraynoic acid and phenidone, are effective in diminishing the CL response. Cyclooxygenase inhibitors, i.e., indomethacin and flurbiprofen, have no or a slight enhancing effect at low doses. These data suggest that at least a major part of the TPA-induced CL response is due to the metabolism of arachidonic acid, most probably by the lipoxygenase(s). This CL assay may provide a useful system for studying the involvement of oxidants in tumor promotion.
Cancer Res 1985 Jul
PMID:Suppression of tumor promoter-induced chemiluminescence in mouse epidermal cells by several inhibitors of arachidonic acid metabolism. 298 61

Hepatic microsomes prepared from rats pretreated with hematoporphyrin derivative (HPD) undergo rapid enhancement of lipid peroxidation in the presence of solar radiation (approximately 400 nm). Quenchers of singlet oxygen, including 2,5-dimethylfuran, histidine, and beta-carotene, and inhibitors of the hydroxyl radical, including benzoate, mannitol, and ethanol, largely protected against the enhancement of lipid peroxidation caused by HPD photosensitization. Catalase, a scavenger of hydrogen peroxide and superoxide dismutase, a scavenger of superoxide anion, had little or no protective effect against HPD-photosensitized enhancement of lipid peroxidation. Our data indicate that in vitro irradiation of hepatic microsomes prepared from HPD-treated rats results in the generation of both singlet oxygen and hydroxyl radical. These reactive moities are associated with a rapid increase in microsomal lipid peroxidation which may explain the unique susceptibility of membranous components of cells to this type of phototoxic injury.
Cancer Res 1985 Dec
PMID:Photoenhancement of lipid peroxidation associated with the generation of reactive oxygen species in hepatic microsomes of hematoporphyrin derivative-treated rats. 299 97

Catalase (CAT), glutathione-peroxidase (GSH-Px) activity and reduced glutathione content (GSH) were measured in patients who had hepatocellular carcinoma, and values compared with those of normal liver and liver adjacent to neoplastic tissue. The results showed a remarkable reduction of CAT in tumor and corresponding tumor-free tissue (P less than 0.001 and P less than 0.02, respectively). All neoplastic samples had a significant lower activity of CAT than the corresponding adjacent tumor-free tissue (P less than 0.05). The GSH-Px activity of tumor tissue also was lower than normal (P less than 0.001) but similar to that of adjacent tissue. No correlation was noted between the two enzyme activities. Glutathione content was extremely low in tumor (P less than 0.001) and even in tumor-free tissue (P less than 0.05) when compared with normal liver. In all cases the content of GSH in neoplastic tissue was lower than that of the corresponding tumor-free tissue (P less than 0.05). Whereas in normal liver the activity of GSH-Px was positively correlated with the content of GSH, in the neoplastic tissue such a relationship disappeared. All these findings suggest that the antioxidant system of hepatocellular carcinoma cell is severely impaired.
Cancer 1986 Oct 15
PMID:Severe impairment of antioxidant system in human hepatoma. 301 7


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