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)

Replacement of media in cell cultures during exposure to hyperoxia was found to alter oxygen toxicity. Following 100 hr of exposure to 95% or 80% O2, the surviving fraction (SF) of Chinese hamster fibroblasts, as assayed by clonogenicity, was less than 1 x 10(-3) when the culture media was replaced only at the onset of the O2 exposure. Media replacement every 24 hr throughout the hyperoxic exposure resulted in SFs of 1.7 x 10(-1) (95% O2) and 1.9 x 10(-1) (80% O2) at 95 hr. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a cytotoxic byproduct of lipid peroxidation, was examined in cells 24 hr following exposure to 80% O2 for 144 hr with media replacement. These O2-exposed cells were resistant to 4HNE, requiring 2.6 times as long in 80 microM 4HNE to reach 30% survival as compared to density-matched normoxia control. Furthermore, during 40 and 60 min of exposure to 4HNE, the O2-preexposed cells metabolized greater quantities of 4HNE (fmole/cell) relative to control. The activity of glutathione S-transferase (GST), an enzyme believed to be involved with the detoxification of 4HNE, was significantly increased in the O2-preexposed cells compared with controls. Catalase activity was significantly increased, but no change was found in total glutathione content, glutathione peroxidase, manganese superoxide dismutase, and copper-zinc superoxide dismutase activities at the time of 4HNE treatment in the O2-preexposed cells relative to density-matched control. The results demonstrate that in vitro tolerance to the cytotoxic effects of hyperoxia can be achieved through media replacement during O2 exposure. Tolerance to oxygen toxicity conferred resistance to the cytotoxic effects of 4HNE, possibly through GST-catalyzed detoxification. These results provide further support for the hypothesis that toxic aldehydic byproducts of lipid peroxidation contribute to hyperoxic injury.
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PMID:Replacement of media in cell culture alters oxygen toxicity: possible role of lipid aldehydes and glutathione transferase in oxygen toxicity. 206 63

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.
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PMID:Resistance mechanisms in three human small cell lung cancer cell lines established from one patient during clinical follow-up. 254 37

Photoemissive excited species are produced by the horseradish peroxidase (HRP)-catalyzed oxidation of reduced glutathione (GSH), without exogenously added hydroperoxide under aerobic conditions. The emitted low-level chemiluminescence consisted of two phases. Light emission occurred at wavelengths beyond 610 nm (greater than or equal to 90% intensity), indicative of singlet oxygen 1O2. Deuterium oxide enhanced photoemission 4.4-fold. Ascorbate inhibited chemiluminescence completely. In the absence of GSH or when GSH was replaced by the disulfide, no red chemiluminescence was observed. The glutathionyl radical GS. is most likely to be involved in both phases of light emission. Further, the superoxide radical plays a role, as substantiated by the inhibitory effect of superoxide dismutase. Both phases of photoemission were abolished by glutathione peroxidase; thus hydroperoxides are regarded as essential intermediates for the formation of excited species. Catalase abolished phase I and did not affect phase II. In contrast, glutathione S-transferase 1-2 (showing peroxidase activity towards organic hydroperoxides but not towards H2O2) inhibited phase II, whereas phase I was still present. Glutathione sulfonate and the disulfide GSSG were detected as oxidation products from GSH under conditions where phase II chemiluminescence was observed. HRP Compound III accumulated during the reaction. It is concluded that phase I is dependent on exogenously added or endogenously generated H2O2, whereas phase II does not require H2O2 but an organic peroxy species. A mechanism based on chain reactions involving oxygen addition to the thiyl radical is proposed. Sulfenyl peroxy species are suggested as transient intermediates in reactions finally leading to the generation of excited states such as singlet molecular oxygen.
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PMID:Excited species generation in horseradish peroxidase-mediated oxidation of glutathione. 301 81

Catalase, superoxide dismutase, and dimethylsulfoxide were tested for their ability to prevent the cytotoxic effect of 6-hydroxydopamine (6-OHDA) on the human neuroblastoma line SY5Y. Viability was measured at two time points after 6-OHDA treatment: at 3 hr by means of amino acid incorporation and at 24 hr by trypan blue dye exclusion. Survival of cells treated concomitantly with catalase (50 microgram/ml) and 6-OHDA was at least 90 per cent that of untreated controls. Cells receiving 6-OHDA alone showed less than 30 per cent survival relative to untreated controls. Superoxide dismutase (50 microgram/ml) temporarily protected cells from a high concentration of 60-OHDA. Dimethylsulfoxide treatment increased survival from the control level 24 hr after treatment with 6-OHDA. Two other cell lines (A1B1 human glial cells and CHO fibroblasts) had intermediate and high resistance to the drug, respectively, compared to the low resistance of SY5Y cells. CHO and SY5Y cells had similar responses to 6-OHDA and to H2O2 when tested at twice the molarity of 6-OHDA. Specific activities of three enzymes known to detoxify H2O2 or H2O2-generated organic hydroperoxides (catalase, glutathione S-transferase, and glutathione peroxidase) were compared in the three cell lines. Catalase activity was 2.5 times as high as in A1B1 and CHO cells as in SY5Y cells when expressed as units/mg protein and 7 times as high in units/culture dish. Other enzyme activities showed no correlation to 6-OHDA resistance.
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PMID:Participation of active oxygen species in 6-hydroxydopamine toxicity to a human neuroblastoma cell line. 705 60

Murine L1210 and human HL-60 leukemia cells grown for 5-7 days in medium containing 1% serum without selenium supplementation [Se(-) cells] were severely depressed in selenoperoxidase (SePX) activity relative to selenium-supplemented controls [Se(+) cells]. Catalase (CAT) activity in Se(-) cells was unaffected up to this point, but thereafter began to increase. Two manifestations of this increase have been differentiated for both cell lines: (a) short-term induction of CAT (up to approx. twofold) after 2-3 weeks, followed by (b) long-term selection for cells that irreversibly express much higher levels of CAT, e.g., > 100 times (L1210) and > 10 times (HL-60) the levels observed in Se(+) controls after approximately 20 weeks. Although superoxide dismutase, glutathione S-transferase, and glucose-6-P dehydrogenase activities were unchanged in Se(-) cells, GSH levels were elevated by 50-100%; like short-term CAT elevation, this could be reversed by supplying Se. Short-term Se(-) cells were more sensitive to H2O2-induced killing than Se(+) cells, evidently because SePX activity was important for peroxide detoxification. However, long-term Se(-) cells were markedly more resistant to H2O2 than Se(+) counterparts, consistent with the much higher levels of CAT in the former. Southern blot analysis revealed that the copy number of CAT DNA in a clone of long-term Se(-) L1210 cells was four- to fivefold greater than that in an Se(+) clone. Northern blot analysis of RNA from the same Se(-) clone showed a CAT mRNA level that was at least 40 times higher than that of the Se(+) control. Similar trends were observed for HL-60 cells. These results suggest that elevated CAT during long-term Se deprivation is a reflection of amplification and greater transcription of the CAT gene.
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PMID:Amplification and hyperexpression of the catalase gene in selenoperoxidase-deficient leukemia cells. 787 6

The human carcinogen, arsenic, is genotoxic to mammalian cells in vitro. The mechanism is largely unknown, although the involvement of free radicals has been suggested. Since the X-ray sensitive Chinese hamster ovary cell line, XRS-5, is also sensitive to several free-radical generating agents, including H2O2, we have used this cell line to test whether the genotoxic effect of arsenite is mediated via the generation of active-oxygen species. The results indicate that the XRS-5 cells are more sensitive to arsenite in terms of cell-killing and micronucleus induction compared to the parental CHO-K1 cells. The level of arsenic uptake and release, the levels of elementary components for arsenic detoxification, glutathione and glutathione S-transferase activities in these two cell lines are very similar. The XRS-5 cells, however, were shown to have 6-fold lower catalase activity in comparison to CHO-K1 cells. Moreover, catalase could effectively reduce the frequency of arsenite-induced micronuclei. These results indicate that the low catalase activity may be an important reason why XRS-5 cells are more sensitive to the toxic effects of arsenite, and arsenite probably induces micronuclei via the overproduction of H2O2. The XRS-5 cells had a higher background level of micronuclei, and were also more sensitive to gamma-rays in terms of induction of micronuclei. Catalase, however, did not reduce the background level or the frequency of gamma-ray-induced micronuclei. Therefore, the lower catalase activity seems to bear little relation to the high background level of micronuclei and the hypersensitivity to gamma-rays in micronucleus induction in XRS-5 cells.
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PMID:Active oxygen species are involved in the induction of micronuclei by arsenite in XRS-5 cells. 793 66

The characteristics of the hepatocarcinogenesis induced by dehydroepiandrosterone (DHEA) were compared with that induced by other peroxisome proliferators such as [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) and di(2-ethylhexyl)phthalate (DEHP). Male F-344 rats were given a diet containing DHEA at 0.5 or 1%, Wy-14,643 at 0.1% and DEHP at 2% for up to 78 weeks. In rats fed 0.5 or 1% DHEA the incidence of neoplasias was 20% after 52 weeks. At 78 weeks all rats treated with 1% DHEA had numerous grossly visible nodules and the incidence of hepatic neoplasia was dose-dependent. The magnitude of hepatocellular tumorigenicity after DHEA treatment was less potent than that after Wy-14,643, but more than that after DEHP treatment. Peroxisomal beta-oxidation activity increased three- or six-fold after a 10 week course of 0.5 or 1% DHEA respectively and this was significantly lower than that induced in Wy-14,643- or DEHP-fed rats. From 52 to 78 weeks these activities increased 3-9 times over that in controls. In both the group of rats treated with Wy-14,643 and those treated with DEHP, peroxisomal beta-oxidation constantly increased 11- to 15-fold during the experiment. Catalase activity increased 1.3- to 1.5-fold for the first 10 weeks of DHEA treatment and then recovered to the control level. The activities of glutathione peroxidase and glutathione S-transferase decreased markedly after 30 weeks in DHEA-treated rats and the decreases were sustained for up to 78 weeks. The profile of changes in enzyme activities in the rats fed DHEA was not significantly different from that of those fed Wy-14,643 or DEHP. There were no increases in 8-hydroxydeoxyguanosine, oxidative DNA damage or lipid peroxide level in the liver in any of the treated rats at 10 or 30 weeks. Since these results showed that the characteristics of hepatocarcinogenesis caused by DHEA were basically similar to those caused by Wy-14,643 and DEHP, typical peroxisome proliferators, hepatocarcinogenesis induced by DHEA is probably due to the same mechanisms as that induced by general peroxisome proliferators.
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PMID:Characteristics of the hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator, in male F-344 rats. 795 56

1. As guinea-pigs have been reported to have a markedly low activity of glutathione peroxidase (GSH-Px), the activity of other hydroperoxide-scavenging enzymes was investigated. 2. Catalase activity in guinea-pig tissues was 2-3 times higher than that of mice or rats. 3. Approximately 90% of catalase activity was found in the soluble fraction of guinea-pig liver, suggesting a compensatory role of catalase in removing H2O2 in the cytosol of guinea-pig tissues. 4. In erythrocytes, GSH-Px activity does not differ among rodents. This may reflect the fact that GSH-Px is the sole enzyme in the removal of organic hydroperoxides in erythrocytes where glutathione S-transferase activity is barely detectable.
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PMID:Species difference in hydroperoxide-scavenging enzymes with special reference to glutathione peroxidase in guinea-pigs. 844 91

The effects of aging on the activities of drug-metabolizing enzymes and antioxidant enzymes were studied in male and female White-Footed mice (Peromyscus leucopus) at ages of 6, 8, 12, 18, 24, 30, 36, and 48 months. Male mice had significantly higher liver microsomal cytochrome P450 (P450) content and NADPH:cytochrome P450 oxidoreductase (P450 reductase) activities than females at all age groups. Many of the P450-dependent enzyme activities were also generally higher in males. Female mice showed age-dependent decreases in P450 content and the activities of P450 reductase, pentoxyresorufin O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMAd) in the liver from 6 to 24 months; while, the males showed an age-dependent decrease only for the liver PROD activity from 6 to 24 months. The old males (30-month old) appeared to have significantly higher activities for 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone and androstenedione formation than the middle-aged (6- to 18-month old) and very old (48-month old) males. Females showed age-dependent decreases for the formation of 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone in liver microsomes from 6 to 24 months. Lung microsomes from 6- and 8-month old males had much higher activities of ethoxyresorufin O-deethylase (EROD) and PROD than older males. The total NNK alpha-hydroxylation activities changed in the same pattern as lung microsomal EROD and PROD activities in both male and female mice. The activities of several phase II drug-metabolizing enzymes: glutathione S-transferase (GST), DT-diaphorase, sulfotransferase and UDP-glucuronosyl-transferase (UDPGT) did not show any significant age-dependent changes, with the possible exception that the GST activity in males decreased from 18 to 36 months. Males had about 3-fold higher UDPGT activities than females among all age groups. Glutathione peroxidase activities were drastically lower in old and very old males, and 6 to 24 months old males had significantly higher activities than the corresponding females. In females, superoxide dismutase activities decreased linearly to extremely low levels as mice aged. Catalase activities showed a tendency for increase with age in males. In conclusion, some P450-dependent activities and antioxidant enzymes, but not phase II drug-metabolizing enzymes, showed age-dependent changes; and most of these changes occur from 6 to 24 months. The demographic attributes of the White-Footed mouse are well-suited for physiological and biochemical studies of aging and can complement the more standard laboratory mouse model with its typical two year life span.
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PMID:Age- and gender-related variations in the activities of drug-metabolizing and antioxidant enzymes in the white-footed mouse (Peromyscus leucopus). 849 97

Free radical metabolism can be altered by several interventions, including dietary restriction (DR) and exercise. Most of the previous work has focused on the liver and skeletal muscle. The following experiments were performed to determine whether long-term DR and chronic exercise affect free radical metabolism and change the status of the antioxidant defenses of the heart. Rats were subjected to DR and/or endurance exercise for 18.5 months and were sacrificed along with their ad lib fed and sedentary controls. Both DR and exercise decreased the malondialdehyde content of cardiac mitochondria, indicating a decrease in lipid peroxidation damage. The antioxidant enzymes in the cytosol, superoxide dismutase, selenium dependent glutathione peroxidase, and glutathione S-transferase were all increased by DR. Catalase activity was unaffected by DR but was increased by exercise. The following results demonstrate that long-term DR and exercise modulate the extent of free radical damage in the heart and enhance the antioxidant defense system.
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PMID:Exercise and diet modulate cardiac lipid peroxidation and antioxidant defenses. 890 82


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