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)

Nitric oxide (NO) induces a covalent modification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from various tissues. This phenomenon, which has previously been interpreted as an auto-ADP-ribosylation, is in fact a covalent binding of NAD+ to the enzyme. In the present study, we show that 3-morpholino-sydnonimine (SIN-1) is much more efficient than sodium nitroprusside (SNP) in stimulating the covalent labelling of GAPDH from cultured striatal neurones in the presence of [adenylate-32P]NAD+ (877 +/- 110 and 266 +/- 33% increase in NAD(+)-labelling induced by maximally effective concentrations of SIN-1 and SNP respectively). The difference in the efficacy of both NO-generating compounds could be due to the additional release of superoxide by SIN-1, since superoxide dismutase and the nitrone 5,5'-dimethyl pyrroline-1-oxide markedly inhibited the SIN-1-induced covalent binding of NAD+ to GAPDH. Catalase and selective scavengers of hydroxyl radicals, mannitol and dimethyl sulphoxide, did not alter the SIN-1-induced covalent modification of GAPDH, ruling out the involvement of hydroxyl radicals in this phenomenon. Supporting further a role of oxygen free radicals in the NAD+ linkage to GAPDH, pyrogallol, a superoxide generator, which alone was ineffective, potentiated the SNP-evoked response. The NAD+ linkage to neuronal GAPDH measured in the presence of NO and superoxide probably involves sulphydryl groups, since the radiolabelling of the protein was reversed by exposure to HgCl2 and prevented by pretreatment with the alkylating agent N-ethylmaleimide. Moreover, the NO-induced inhibition of GAPDH activity was enhanced by pyrogallol, which was ineffective alone. In conclusion, the present study indicates that superoxide anions potentiate NO-induced covalent NAD(+)-linkage to GAPDH and enzyme inactivation.
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PMID:Oxygen free radicals enhance the nitric oxide-induced covalent NAD(+)-linkage to neuronal glyceraldehyde-3-phosphate dehydrogenase. 763 7

Hydrogen peroxide-resistant Chinese hamster ovary (CHOR) cells were developed by exposing parental (CHO(P)) cells to sequential increases in H2O2 concentration. Cytotoxicity as well as DNA single-strand breaks induced by Na2CrO4 were then compared in CHOR and CHO(P) cell lines. Using the colony-forming assay, it was found that the cytotoxicity caused by Na2CrO4 did not differ in the parent and resistant cells. However, alkaline elution studies showed that the production of DNA single-strand breaks in CHOR cells treated with Na2CrO4 was reduced by about 50% as compared with that in CHO(P) cells. Similarly, electron spin resonance (ESR) studies revealed that the level of chromium(V) in CHOR cells during treatment with Na2CrO4 was about 50% that in CHO(P) cells. CHOR cells were also found to be cross-resistant to the cytotoxicity and DNA breaks caused by other toxic metals such as CdCl2 and HgCl2. Catalase activity in resistant cells was 2-fold and the cellular content of glutathione was 3-fold that in parental cells. However, no obvious differences were seen in superoxide dismutase and glutathione reductase activity, although the contents of ascorbic acid or alpha-tocopherol were slightly decreased in CHOR cells, suggesting that the resistance in CHOR cells may be associated with the increase in both catalase activity and glutathione contents in cells. These results indicate that chromate-induced DNA breaks appear to be mediated by a different mechanism than that for the cytotoxicity of this metal, and also suggest that the formation of active oxygen species and/or chromium(V) during reduction of chromium(VI) inside cells might be associated with the induction of the DNA strand breaks caused by the metal.
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PMID:DNA single-strand breaks and cytotoxicity induced by sodium chromate(VI) in hydrogen peroxide-resistant cell lines. 768 Apr 28

The effect of mercury as Hg2Cl2 and HgCl2 on the antioxidant enzyme levels and its toxicity was investigated in an insect model comprised of adult females of the common housefly, Musca domestica, and fourth-instar larvae of the cabbage looper moth, Trichoplusia ni. HgCl2 was found to be more toxic than Hg2Cl2 to both M. domestica and T. ni. The LC50s for M. domestica were 1.17% and 0.38% w/v concentration for Hg2Cl2 and HgCl2, respectively. For the more tolerant T. ni, the LC50S were 5.15% for Hg2Cl2 and 0.96% w/w concentration for HgCl2. The minimally acute LC5 dose of both oxidation states of Hg was approximately 0.005% for both insects (w/v for M. domestica and w/w for T. ni). At the LC5, both forms of Hg significantly induced the activity of superoxide dismutase in both insect species. Catalase was induced by both Hg2Cl2 and HgCl2 in M. domestica but was only induced by HgCl2 in T. ni. Glutathione-S-transferase, its peroxidase activity, and glutathione reductase activities were also significantly altered in most cases by Hg in both insects although the pattern of alternation was different between the two insects. It is evident that mercury induces oxidative stress in insects as it does in vertebrates. Our findings suggest that insects may serve as a valuable, non-mammalian model species to assess Hg-induced oxidative stress as a component of environmental toxicity.
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PMID:An insect model for assessing mercury toxicity: effect of mercury on antioxidant enzyme activities of the housefly (Musca domestica) and the cabbage looper moth (Trichoplusia ni). 811 20

We have isolated and conducted preliminary characterization of a cell line derived from the Chinese hamster ovary cell line AA8, which we have designated AG8 and which is highly resistant to the cytotoxic effects of H2O2 (approximately 17-fold when the H2O2 treatment was at 37 degrees; approximately 11-fold when the H2O2 treatment was at 4 degrees). AG8 cells were moderately (but significantly; P < 0.05) cross-resistant to CdCl2 (approximately 4-fold), NaAsO2 (approximately 2.3-fold), t-butyl hydroperoxide (approximately 2.9-fold), cumene hydroperoxide (approximately 3-fold), menadione (approximately 1.7-fold) and HgCl2 (approximately 1.5-fold), but were not significantly cross-resistant to hyperthermia (43 degrees), 254 nm UV light, 137Cs gamma-rays, and 42-MeV (p-->Be+) fast neutrons. As regards their biochemical status, AG8 and AA8 cells contain similar non-protein sulfhydryl levels per milligram of protein. Catalase activity (assessed by both spectrophotometry and polarography) was significantly higher in AG8 than in AA8 cells irrespective of whether enzyme activity was expressed per 10(6) cells (approximately 3.6-fold increase) or per milligram of protein (approximately 1.6-fold increase). AG8 cells also exhibited significantly greater glutathione reductase activity than wild-type cells when the data were expressed per 10(6) cells (approximately 2.9-fold) or per milligram of protein (approximately 1.3-fold). Glutathione peroxidase activity was immeasurably low in both cell lines. The susceptibility of the two cell lines to H2O2-mediated generation of DNA single-strand breaks (as measured by alkaline elution) indicated a slightly (approximately 1.5-fold) decreased yield in the resistant AG8 cell line. The two cell lines repaired these breaks with similar kinetics. In contrast, no measurable induction of DNA double-strand breaks (as measured by pulsed-field gel electrophoresis) was apparent in either cell line after survival-curve range concentrations of H2O2. On the basis of these data, it appears that the AG8 phenotype involves two previously identified resistance mechanisms, namely an adaptive component that may or may not involve increased antioxidant capacity, and a second component that does involve increased antioxidant (primarily catalase) capacity.
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PMID:Isolation and preliminary characterization of a Chinese hamster ovary cell line with high-degree resistance to hydrogen peroxide. 886 24

The role of oxidative stress in mercuric chloride (HgCl2)-induced nephrotoxicity is uncertain and controversial. We demonstrate that I.L.C-PK1 cells, exposed to HgCl2, generate massive amounts of hydrogen peroxide, the latter completely quenched by the hydrogen peroxide scavenger, pyruvate. HgCl2 exerts a dose-dependent cytotoxicity which is attenuated by pyruvate and catalase. Cellular generation of hydrogen peroxide arises, at least in part, from mitochondria since mitochondrial rates of generation of hydrogen peroxide increase in response to HgCl2; HgCl2 also provokes a shift in absorbance spectra in rhodamine 123 loaded-mitochondria and stimulates mitochondrial state 4 respiration. HgCl2, applied for one hour, impairs cellular vitality as demonstrated by the MTT assay, an assay dependent in part on mitochondrial function. HgCl2 impairs function in other organelles such as lysosomes that maintain a transmembrane proton gradient; these latter effects are partially attenuated by pyruvate. We complement these in vitro findings with in vivo evidence demonstrating that HgCl2 stimulates renal generation of hydrogen peroxide. The functional significance of such generation of hydrogen peroxide was evaluated in rats deficient in selenium and vitamin E, a nutrient deficiency that impairs the scavenging of hydrogen peroxide and promotes the toxicity of this oxidant. In these rats serum creatinine values were significantly higher on sequential days following the administration of HgCl2. To probe the renal response to oxidative stress induced by HgCl2, we examined hydrogen peroxide-scavenging enzymes and redox-sensitive genes. Catalase activity was unaltered whereas glutathione peroxidase activity was decreased, effects that may contribute to the net renal generation of hydrogen peroxide. The redox sensitive enzyme, heme oxygenase, was markedly up-regulated in the kidney in response to HgCl2. HgCl2 also induced members of the bcl family, bcl2 and bclx, genes that protect against apoptosis and oxidant injury. In another model of oxidant-induced renal injury, the glycerol model, bcl2 mRNA was not induced at 6 and 24 hours after the administration of glycerol. In summary, we demonstrate that HgCl2 potently stimulates renal generation of hydrogen peroxide in vitro and in vivo and such generation of peroxide contributes to renal dysfunction in vitro and in vivo. We also demonstrate that in response to HgCl2, redox sensitive genes are expressed including heme oxygenase and members of the bcl family.
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PMID:Renal oxidant injury and oxidant response induced by mercury. 887 81

The study was aimed to evaluate the possible effects of dexamethasone on oxidant/antioxidant status in kidney tissues of rats administered mercuric chloride (HgCl2). Thirty male Wistar-albino rats were enrolled in this study. Rats were divided into 4 groups: G1 (n=7) underwent no therapy (control group), G2 (n=8) received HgCl2 + physiological saline, G3 (n=7) dexamethasone (DM) + physiological saline and G4 (n=8) received HgCl2 + DM. HgCl2 was injected subcutaneously into rats in the G2 and G4 on the first day of the study. Dexamethasone was injected intraperitoneally into rats in the G3 and G4 for 3 days. Malondialdehyde (MDA) levels, catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and superoxide dismutase (SOD) activities were evaluated in the kidney tissues. Serum creatinine levels were also measured. Xanthine oxidase activity was increased in the G2 compared to the control group. Catalase activity in the control group was significantly higher compared to the other groups. In the histopathological examination of kidneys, there was a tubular degeneration in G2 and G4. It was concluded that HgCl2 administration may cause oxidative stress through increasing XO and decreasing CAT activities. Dexamethasone injection may partially protect the rat kidneys against oxidative reactions by preventing the increase in XO activity (Tab. 1, Ref. 33).
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PMID:The effects of dexamethasone on oxidant/antioxidant status in kidneys of rats administered mercuric chloride. 2238 Apr 94

Organic and inorganic forms of mercury are highly neurotoxic environmental contaminants. The exact mechanisms involved in mercury neurotoxicity are still unclear. Oxidative stress appears to play central role in this process. In this study, we aimed to validate an insect-based model for the investigation of oxidative stress during mercury poisoning of lobster cockroach Nauphoeta cinerea. The advantages of using insects in basic toxicological studies include the easier handling, rapid proliferation/growing and absence of ethical issues, comparing to rodent-based models. Insects received solutions of HgCl2 (10, 20 and 40mgL(-1) in drinking water) for 7d. 24h after mercury exposure, animals were euthanized and head tissue samples were prepared for oxidative stress related biochemical determinations. Mercury exposure caused a concentration dependent decrease in survival rate. Cholinesterase activity was unchanged. Catalase activity was substantially impaired after mercury treatment 40mgL(-1). Likewise, GST had a significant decrease, comparing to control. Peroxidase and thioredoxin reductase activity was inhibited at concentrations of 20mgL(-1) and 40mgL(-1) comparing to control. These results were accompanied by decreased GSH levels and increased hydroperoxide and TBARS formation. In conclusion, our results show that mercuric compounds are able to induce oxidative stress signs in insect by modulating survival rate as well as inducing impairments on important antioxidant systems. In addition, our data demonstrates for the first time that Nauphoeta cinerea represents an interesting animal model to investigate mercury toxicity and indicates that the GSH and thioredoxin antioxidant systems plays central role in Hg induced toxicity in insects.
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PMID:Is the lobster cockroach Nauphoeta cinerea a valuable model for evaluating mercury induced oxidative stress? 2346 93

Mercury, a prevalent and unrelenting toxin, occurs in a variety of forms in freshwater as well as, in marine life. Mercury is an important inducer of oxidative stress in fish leading to formation of reactive oxygen species. Selenium is an essential micronutrient for animals and has antagonistic effect against mercuric toxicity in fishes. Present study has been made to evaluate toxic effect of HgCl2 (0.15 mg/L) on liver of freshwater catfish Heteropneustes fossilis (Bl.). Protective ability of selenium has been investigated by simultaneous exposure of fish with sodium selenite (0.15 mg/L) along with mercuric chloride. For present study Fishes were divided into three groups of ten fishes each the first group served as control, while the second group fish were exposed to HgCl2 . Animals of third group were treated with HgCl2 and Na2 SeO3 . Results reveal that mercury induced lipid peroxidation and in response to this, antioxidants reduced glutathione (GSH) and Catalase (CAT) were reduced whereas, Glutathione reductase (GR) level was enhanced. These antioxidants scavenge the reactive oxygen radicals. Hg induced histopathological damage and elevation in alkaline phosphatase (ALP) and transaminases and reduction in protein and glucose contents were evidently seen in catfish liver. Intriguingly, results indicate that under stress of mercury, the fish actively generate oxidative stress and antioxidant responses, which can be used as biomarkers of pollution. Simultaneous exposure to Selenium along with Hg suppressed Hg uptake and lipid peroxidation. Histological architecture and all biochemical parameters were maintained near normal in the presence of selenium in liver of the catfish.
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PMID:Ameliorative stroke of selenium against toxicological effects of mercuric chloride in liver of freshwater catfish Heteropneustes fossilis (Bloch). 2450 Sep 73