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)

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

Cardiotoxicity is the main dose-limiting side effect of doxorubicin in the clinic. Being a free radical producer, doxorubicin affects the heart specifically because of its low antioxidant capacity. Among those antioxidants, catalase is present in very low levels in the heart compared to other organs. Since catalase is an essential enzyme in detoxifying hydrogen peroxide, the aim of the present study was to investigate the protective effect of catalase as delivered by an adenovirus vector against doxorubicin-induced cardiotoxicity in cultured neonatal rat cardiac myocytes (NeRCaMs). 7-Monohydroxyethylrutoside (MonoHER), a potent cardioprotector currently under clinical investigations, was included in the study as a reference. Neonatal rat cardiac myocytes were infected with different multiplicity of infections (MOIs) of adenovirus encoding catalase (AdCat). A control infection with an adenovirus vector encoding a nonrelated protein was included. The activity and content of catalase in infected cells were determined during 3 days postinfection. One group of NeRCaMs was infected with AdCat before treatment with doxorubicin (0-50 microM). The second and third group were treated with doxorubicin (0-50 microM) with and without 1 mM monohydroxyethylrutoside (monoHER), respectively. The LDH release and viability of treated cells were measured 24 and 48 h after doxorubicin treatment. The beating rate was followed in three other groups of cells receiving the same treatments within 3 days after doxorubicin (0-100 microM) treatment. Catalase activity increased in AdCat-infected cells, with different MOIs, starting from the second day after infection as compared to the mock-infected cells (P<0.03). At the third day of infection, an MOI of more than 50 caused cytopathic effects, which hampered the use of higher viral titres. With an MOI of 50, catalase activity increased 3.5-fold in AdCat-infected cells 3 days postinfection (P=0.021) compared to mock-infected cells. The beating rate and survival of NeRCaMs decreased in a concentration and time-dependent manner after doxorubicin treatment (P<0.0005). This cytotoxicity was associated with an increase in the LDH release from the treated cells (P<0.0005). The cells stopped beating 24 h after treatment with >50 microM doxorubicin. A 3.5-fold increase in the activity of catalase did not protect NeRCaMs against any of the cytotoxic effects of doxorubicin on NeRCaMs. In contrast, monoHER (1 mM) significantly protected NeRCaMs against the lethal effects of doxorubicin on the survival, LDH release and the beating rate of NeRCaMs (P<0.004) during 48 h after doxorubicin treatment. This protection resulted in a prolongation of the beating of doxorubicin-treated cells after the end of the experiment (i.e. >72 h). The present study (1) illustrates that the cytotoxicity of high MOI of AdCat (>50) limited the possibility to increase catalase activity more than 3.5-fold, which was not enough to protect infected NeRCaMs against doxorubicin-induced cardiotoxicity and (2) confirms the efficacy of monoHER as a cardioprotector. Thus, the use of monoHER proves more suitable for the prevention of doxorubicin-induced cardiotoxicity than catalase gene transfer employing adenovirus vectors.
Br J Cancer 2003 Dec 01
PMID:A comparative study between catalase gene therapy and the cardioprotector monohydroxyethylrutoside (MonoHER) in protecting against doxorubicin-induced cardiotoxicity in vitro. 1464 50

We present the results of the first theoretical investigation of salen-manganese complexes as synthetic catalytic scavengers of hydrogen peroxide molecules that mimic catalase enzymes. Catalase mimics can be used as therapeutic agents against oxidative stress in treatment of many diseases, including Alzheimer's disease, stroke, heart disease, aging, and cancer. A ping-pong mechanism approach has been considered to describe the H2O2 dismutation reaction. The real compounds reacting with a peroxide molecule were utilized in our BP density functional calculations to avoid uncertainties connected with using incomplete models. Part I of the dismutation reaction-converting a peroxide molecule into a water molecule with simultaneous oxidation of the metal atom of the catalyst-can be done quite effectively at the Mn catalytic center. To act as catalytic scavengers of hydrogen peroxide, the oxomanganese salen complexes have to be deoxidized during part II of the dismutation reaction. It has been shown that there are two possible reaction routes for the second part of the dismutation reaction: the top and the side substrate approach routes. Our results suggest that the catalyst could be at least temporarily deactivated (poisoned) in the side approach reaction route due to the formation of a kinetically stable intermediate. Overall, the side approach reaction route for the catalyst recovery is the bottleneck for the whole dismutation process. On the basis of the detailed knowledge of the mode of action of the (salen)MnIII catalase mimics, we suggest and rationalize structural changes of the catalyst that should lead to better therapeutic properties. The available experimental data support our conclusions. Our findings on the reaction dismutation mechanism could be the starting point for further improvement of salen-manganese complexes as synthetic catalytic scavengers of reactive oxygen species.
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PMID:(salen)MnIII compounds as nonpeptidyl mimics of catalase. Mechanism-based tuning of catalase activity: a theoretical study. 1573 83

Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (p<0.01) reduction of the incidence and number of skin papillomas, precancerous skin lesions, along with significant (p<0.01) elevation of phase II detoxifying enzymes (GST, Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy.
Asian Pac J Cancer Prev
PMID:Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis. 1610 30

Nitrosamine compounds are known hepatic carcinogens. In the metabolism of nitrosamines, such as N-nitrosodiethylamine (NDEA), there is evidence of the formation of reactive oxygen species (ROS) resulting in oxidative stress, which may be one of the factors in the etiology of cancer. The formation of ROS may alter the antioxidant system, while the presence of Vitamin E may counteract NDEA induced oxidative stress. This study was planned to determine whether pre-treatment with Vitamin E (40 mg/kg body weight, i.p., twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress in liver caused by the carcinogen. A single necrogenic dose of NDEA (200mg/kg body weight) was administered i.p. to the male albino rats with or without Vitamin E pre-treatment and the animals were sacrificed on Days 7, 14 or 21 after the administration of NDEA. The result showed enhanced levels of hepatic lipid peroxidation (LPO) and conjugated dienes of NDEA treated rats as the indices of oxidative stress, however, Vitamin E pre-treated rats administered NDEA showed decreased LPO and conjugated dienes (Day 21). Superoxide dismutase (SOD) activity in liver was not altered significantly in NDEA treated rats with or without Vitamin E pre-treatment. Catalase (CAT) activity was inhibited with NDEA treatment, however, Vitamin E pre-treatment showed recovery in hepatic CAT activity (Days 14 and 21). Total and Se-glutathione peroxidase (GSH-Px) activities and glutathione-S-transferase (GST) activity in liver increased in NDEA treated rats irrespective of Vitamin E pre-treatment. Glutathione reductase (GSH-R) activity as well as total glutathione (GSH) content in liver decreased in NDEA treated animals, both of which were recovered in Vitamin E pre-treated rats administered NDEA. Activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were increased significantly following NDEA treatment to rats with or without Vitamin E pre-treatment. The activities of AST and ALT enzymes were significantly reduced on Days 14 and 21 and ALP activity was reduced on Day 21 in NDEA+Vitamin E treated animals when compared to NDEA treated alone. LDH enzyme activity was normalized on Day 14 in Vitamin E pre-treated animals administered NDEA. However, the AST, ALT and ALP enzyme activities remained high in all treatment groups as compared to control group. Normal control and Vitamin E treated alone rats revealed normal histology of liver. On the other hand, NDEA treated animals showed alterations in normal hepatic histoarchitecture, which comprised of necrosis and vacuolization of the cells. However, the rats treated with Vitamin E+NDEA showed that the liver cells were normal, with very little necrosis (Day 21). This study concludes that the pre-treatment with Vitamin E prior to the administration of NDEA, reduced the degree of oxidative stress, although this vitamin produced only slight changes in the hepatic injury, in a time-dependent manner.
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PMID:Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver. 1614 95

An increased catalase activity in Candida spp. has been suggested as a mechanism that reduces amphotericin B activity. Furthermore, resistance to antifungal agents like amphotericin B has been reported in some cancer patients undergoing chemotherapy treatment. In this study we analysed the influence of chemotherapy agents on catalase activity in Candida albicans, the major species involved in yeast infections. Eight strains of C. albicans isolated from HIV-positive patients were exposed to cyclophosphamide, cytarabine, dacarbazine and methotrexate antineoplastic drugs at the concentrations used during therapy. Catalase activity was measured and compared to the control group. Very significant differences (P < 0.01) were found when C. albicans was exposed to methotrexate (2 microg ml(-1) = 4 microM). For cyclophosphamide (50 microg ml(-1)), cytarabine (1 microg ml(-1)) and dacarbazine (8 microg ml(-1)), no differences were found (P > 0.05) between the control and drug-exposed groups. Although more extensive studies are necessary, these data do suggest that the antineoplastic drug methotrexate contributes to the resistance to antifungal drug therapy by varying catalase activity.
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PMID:Catalase activity in Candida albicans exposed to antineoplastic drugs. 1647 88

Catalase is an endogenous antioxidant enzyme that neutralizes hydrogen peroxide and is induced by oxidative challenge. A -262C --> T polymorphism in the promoter region of the gene (CAT) is associated with risk of several conditions related to oxidative stress. We sought to determine the functional effects of the CAT polymorphism on enzyme activity in erythrocytes and the potential modifying effects of demographic and lifestyle factors on genotype/phenotype relationships, using specimens and data from controls from breast and prostate cancer studies in Arkansas (n = 420). There was a dose-response reduction in catalase activity by genotype, with geometric means of 115.4 units/mg hemoglobin for those with CC genotypes, 82.1 units/mg for those with CT genotypes, and 73.5 units/mg for those with TT genotypes. Associations were only observed among Caucasians (P < 0.0001), with no effects among African Americans (P = 0.91), and were stronger among women than men, although numbers in stratified analyses were small. Differences in catalase activity by genotype were most pronounced among those in the highest tertiles of consumption of fruits and vegetables (-35%, P = 0.003), with weaker relationships among those who were lower consumers (-21.8%, P = 0.16). Among those with CC genotypes, there was no change in activity by consumption, but there were notable decreases in activity by tertiles of consumption for those with at least one T allele. These data indicate that the CAT -262C --> T polymorphism predicts a portion of catalase phenotype, which may be limited to Caucasians. Associations between genotype and phenotype were modified by dietary factors, illustrating the biochemical complexity of studies of genetic polymorphisms and disease risk.
Cancer Epidemiol Biomarkers Prev 2006 Jun
PMID:Associations between catalase phenotype and genotype: modification by epidemiologic factors. 1677 84

The ionizing radiation used in cancer therapy frequently produces damage to normal tissues and induces complex responses, including inflammation. The upregulation of the intercellular adhesion molecule-1 (ICAM-1) in response to numerous inducing factors is associated with inflammation. Therefore, this study examined the molecular mechanisms responsible for ICAM-1 expression induced by gamma-irradiation (gammaIR). ICAM-1 mRNA and cell surface expression were induced in A549 human lung epithelial cells after exposing them to gammaIR. Catalase expression and activity were also increased in gammaIR-treated cells. Treatment of the gammaIR-treated cells with catalase resulted in a significant increase in the ICAM-1 cell surface expression level. The catalase inhibitor 3-amino-1,2,4-triazole (AT) reduced the level of ICAM-1. Electrophoretic mobility shift assay (EMSA) analysis showed that activating protein 1 (AP-1) was activated by gammaIR, whereas NF-kappaB was not. Specific Jun N-terminal kinase (JNK) inhibition attenuated the upregulation of gammaIR stimulated ICAM-1. Western blot analysis revealed a marked elevation in activation of JNK. In addition, pretreatment with AT resulted in a decrease in the level of JNK phosphorylation and AP-1 activation. Overall, data suggest that induction of ICAM-1 expression by gammaIR is associated with catalase. Furthermore, catalase, JNKs, and AP-1 activation induce ICAM-1 upregulation through a sequential process.
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PMID:Gamma-irradiation-induced intercellular adhesion molecule-1 (ICAM-1) expression is associated with catalase: activation of Ap-1 and JNK. 1706 5

We found previously that the human lung benzo(a)pyrene (BP)-7,8-diol-9,10-epoxide-N(2)-deoxyguanosine (BPDE-dG) adduct concentrate in the target bronchial cells. This adduct is now considered to be critical event in tumorigenesis by BP. In this study, we investigate the contribution of cigarette smoke on the BPDE-dG formation. In a cell-free system, the amount of (-)-anti-BPDE-dG adduct increased linearly with concentration of cigarette smoke in the presence of (+)-BP-7,8-diol. Catalase and superoxide dismutase inhibited its formation by >80%. When MCF-7 cells were treated for 2 hours with the (+)-BP-7,8-diol, cigarette smoke increased dose dependently the formation of (-)-anti-BPDE-dG and decreased the cytochrome P450 (CYP)-dependent formation of (+)-r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydro-BP the adduct. Then, cells were treated for up to 1 day with BP and then exposed for 2 hours with cigarette smoke. During these 2 hours, there are twice the increase in the adduct formation in cells treated with cigarette smoke compared with levels in nontreated cells due to CYP activity. Thus, cigarette smoke containing reactive oxygen species may activate the second step of BP metabolic way, leading to the formation of BPDE-dG adduct. Cigarette smoke thus seems may be in part responsible for the formation of the critical lung tumorigenic adduct. Finally, modified cigarette filter containing rosemary extract decreases by >70% of the BPDE-dG adducts level due to the cigarette smoke in MCF-7 cells. This approach may lead to decreasing lung cancer risk in addicted smokers.
Cancer Res 2006 Dec 15
PMID:DNA damage by benzo(a)pyrene in human cells is increased by cigarette smoke and decreased by a filter containing rosemary extract, which lowers free radicals. 1717 92

Serum and tumor copper levels are significantly elevated in a variety of malignancies including breast, ovarian, gastric, lung, and leukemia. D-Penicillamine (D-pen), a copper-chelating agent, at low concentrations in the presence of copper generates concentration-dependent cytotoxic hydrogen peroxide (H(2)O(2)). The purpose of these studies was to investigate the in vitro cytotoxicity, intracellular reactive oxygen species (ROS) generation, and the reduction in intracellular thiol levels due to H(2)O(2) and other ROS generated from copper-catalyzed D-pen oxidation in human breast cancer cells (BT474, MCF-7) and human leukemia cells (HL-60, HL-60/VCR, HL-60/ADR). D-pen (< or = 400 microM) in the presence of cupric sulfate (10 microM) resulted in concentration-dependent cytotoxicity. Catalase was able to completely protect the cells, substantiating the involvement of H(2)O(2) in cancer cell cytotoxicity. A linear correlation between the D-pen concentration and the intracellular ROS generated was shown in both breast cancer and leukemia cells. D-pen in the presence of copper also resulted in a reduction in intracellular reduced thiol levels. The H(2)O(2)-mediated cytotoxicity was greater in leukemia cells compared to breast cancer cells. These results support the hypothesis that D-pen can be employed as a cytotoxic copper-chelating agent based on its ROS-generating ability.
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PMID:Copper chelation by D-penicillamine generates reactive oxygen species that are cytotoxic to human leukemia and breast cancer cells. 1789 40


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