Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of chemically induced hepatic injury on biotransformation enzymes in fish were studied. Sunfish hybrids (Lepomis macrochirus x L. cyanellus) were dosed per os with allyl formate (ALF) and carbon tetrachloride (CCl4), and the induction of liver EROD (7-ethoxyresorufin O-deethylase) activity was subsequently challenged by injections of beta-naphthoflavone (BNF) and benzo[a]pyrene (B[a]P). Hepatotoxicity of chemical treatments was assessed using blood enzymes (ASAT, ALAT, and LDH) along with other biochemical variables. Both hepatotoxicants partially abolished the induction of EROD (maximally by 76-89%), and the decrease in induction was dose related. The cytosolic activity of glutathione S-transferase (GST) in the liver decreased in parallel with the decrease in EROD induction. Fish receiving high doses of ALF exhibited significantly less microsomal and blood plasma proteins and, occasionally, were jaundiced. These symptoms, however, were less sensitive indicators of hepatotoxicity than alterations in liver EROD and GST. Both ALF and CCl4 increased the activities of hepatic enzymes in the blood plasma, indicating cytotoxicity. In addition B[a]P, unlike BNF, also increased plasma activities of LDH and ALAT at a dose inducing liver EROD, implying simultaneous hepatotoxicity at high sublethal levels of this xenobiotic. These data suggest that hepatotoxic chemicals absorbed by fish may act antagonistically by decreasing the degree of induction of the cytochrome P450 system relative to the inherent capacity of inducing xenobiotic chemicals present in the environment. Therefore, when assessing the toxicological status of water using fish health biomarkers, it is advisable to measure a concert of metabolic and biochemical variables instead of any single biomarker.
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PMID:Effects of hepatotoxicants on the induction of microsomal monooxygenase activity in sunfish liver by beta-naphthoflavone and benzo[a]pyrene. 137 51

The appearance of differentiated hepatocytes in the adult rat pancreas as well as pancreatic-type tissue in the adult rat liver can be experimentally induced (Reddy et al.: J. Cell Biol., 98:2082-2090, 1984; Rao et al., J. Histochem. Cytochem., 34:197-201, 1986). These observations suggest a lineage relationship between cell compartments present in rat liver and pancreas. The present data demonstrate that epithelial cell lines with almost identical phenotypes can be established from adult rat liver and pancreas. The established cell lines showed similar morphologies as established by light- and electron-microscopic studies. The cell lines showed a unique expression pattern of intermediate filament proteins. Vimentin, actin, and beta-tubulin were present in all cell lines. In addition, simple epithelial type II cytokeratins 7 and 8 were found to be coexpressed with the type I cytokeratin 14 in several of the cell lines. Neither the type I cytokeratins 18 and 19, which are the normal partners for cytokeratins 8 and 7 in filament formation, nor the type II cytokeratin 5 could be detected despite the fact that filaments were formed by both cytokeratins 8 and 14. This suggests that cytokeratin 14 acts as an indiscriminate type I cytokeratin in filament formation in the established cell lines. The cell lines expressed the same sets of LDH and aldolase isoenzymes and identical sets of glutathione transferase subunits. In addition, the epithelial cell lines from liver and pancreas were equally sensitive to the growth-inhibitory effects of TGF-beta 1. No expression of tissue- or cell-specific proteins such as alpha-fetoprotein, albumin, amylase, elastase, or gamma-glutamyl transpeptidase were detected. The almost identical phenotypes of the hepatic and pancreatic cell lines suggest that they may be derived from a common primitive epithelial cell type present in both rat liver and pancreas. In contrast to parenchymal cells, these cells have an extended capacity for proliferation in vitro and may represent a progeny from a "precursor" or "stem" cell compartment in vivo.
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PMID:Evidence for a common cell of origin for primitive epithelial cells isolated from rat liver and pancreas. 171 Feb 29

Anthraquinone dyes are utilized by the military in colored-smoke grenades. During production, workers in munitions plants may be exposed to fugitive emissions of these dyes or mixtures thereof. The effects of a prototype violet dye mixture (VDM) consisting of Disperse Red 11 (DR11), [1,4-diamino-2-methoxy-anthraquinone] and Disperse Blue 3 (DB3) [1-methylamino-4-hydroxyethylamino-anthraquinone] on F344 male and female rats have been investigated. Acute 1-day inhalation exposures (6 hr) to VDM were conducted at 1000, 300, 100, 70, 40, and 10 mg/m3, with an additional exposure to 40 mg/m3 6 hr/day for 5 days; 4.22 +/- 2.1 microns (MMAD +/- delta g). Lung burdens of dye, general histopathology, and/or liver function were evaluated at 0, 3, and 7 days postexposure. Unexpected lethality due to severe liver damage was observed with acute exposures of > or = 300 mg/m3 and in the 5-day 40 mg/m3 exposures. Centrilobular degeneration and necrosis of liver cells was concentration-dependent with inhalation of VDM > or = 40 mg/m3. In addition, nasal olfactory epithelium exhibited degeneration and necrosis with acute exposures > or = 10 mg/m3. Lung instillations at 250, 500, and 1000 micrograms of the VDM revealed no lung or liver toxicity. Because per os exposure due to preening was suspected as a major exposure route, a gavage study with the VDM and its two component dyes DR11 and DB3 (800 mg/kg) was undertaken. One day following gavage with DR11 or DB3, serum enzymes indicative of liver toxicity (LDH, SGPT, SDH, and ICDH) were slightly elevated (1-6x control). However, rats gavaged with VDM had serum enzyme levels 10-100x control by Day 1 after gavage, indicating acute liver toxicity. Activities of liver enzymes involved in xenobiotic and glutathione metabolism were also acutely affected. All of the dyes caused various degrees of induction of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and nonprotein sulfhydryls. The enzymes involved in xenobiotic metabolism (glutathione S-transferase, NADPH cytochrome-c reductase, and P450) were also elevated by the two component dyes, in contrast to their significant depression with VDM treatment. The similarity between the liver and olfactory epithelium effects of these compounds and the lack of pulmonary tissue effects is not fully understood, but the interaction of the individual dyes as VDM emphasizes the need to assess chemicals such as the anthraquinones as their likely-to-be-encountered mixtures.
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PMID:Toxicity of an anthraquinone violet dye mixture following inhalation exposure, intratracheal instillation, or gavage. 812 3

A survey was conducted to study the genetic differentiation among 16 tribal groups of Orissa, Madhya Pradesh, and Maharashtra belonging to different ethnic and linguistic affiliations. Sixteen hundred and fifteen blood samples from both sexes were tested for 5 red cell enzyme systems: ACP, ESD, PGD, GLO, LDH, and Hb pattern. Three hundred and nineteen male individuals were tested for G-6-PD enzyme deficiency. The distribution of the enzyme markers and Hb show a range of variation which are more or less within the Indian range. Cases of homozygous HbSS were detected in all the tribes except 3 tribes in Orissa. Two cases of LDH Cal-1 homozygote were found in two Dravidian language speaking Orissa tribes. The chi 2-values for testing the homogeneity of gene frequencies indicate a non-significant heterogeneity for all alleles in the individual system. Within population diversity seems to be larger than between population diversity. The degree of over all genetic differentiation as measured by GST value is 0.0154 +/- 0.0071.
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PMID:Study of enzyme polymorphism and haemoglobin patterns amongst sixteen tribal populations of central India (Orissa, Madhya Pradesh, and Maharashtra). 826 Jul 22

Initiated/selected (ISH) and normal (NH) rat hepatocytes were used to study cytoskeleton modifications induced by three liver acting chemicals: 2-AAF, a liver complete carcinogen; PB, a liver tumor promoter; and 4-AAF, a non-carcinogen analogue of 2-AAF. Cytoskeleton alterations were visualized by disappearance of F-actin fibers and tubulin depolymerization. The three drugs induced actin fragmentation in normal hepatocytes; a net loss of actin protein was observed with PB. They also induced varied tubulin depolymerization. The principal difference between chemicals is that 2-AAF led to non-reversible effects, in comparison with PB and 4-AAF which induced reversible damages on cytoskeleton. By contrast to normal hepatocytes, the cytoskeleton of ISH obtained from rats subjected to the "resistant" hepatocyte protocol was much less susceptible to the effect of the three chemicals. Moreover, we observed a lack of LDH release in the culture medium and a very rapid inducibility of GST activity after exposure of ISH to drugs. The moderate effect of the three chemicals on actin and tubulin in ISH could thus be explained by the "resistant" metabolic profile of these cells.
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PMID:Cytoskeleton modifications induced by phenobarbital, 2-acetylaminofluorene and 4-acetylaminofluorene in normal and initiated/selected hepatocytes: relation with the "resistant" phenotype. 851 70

Mutations in the beta-amyloid precursor protein (APP) gene cause familial Alzheimer's disease (AD). Although amyloid beta peptide (Abeta) is the principal constituent of senile plaques in AD, other cleavage products of APP are also implicated in playing a role in the pathogenesis of AD. C-terminal fragments of APP (APP-CTs), that contain complete Abeta sequence, are found in neuritic plaques, neurofibrillary tangles and the cytosol of lymphoblastoid cells obtained from AD patients. Our previous report demonstrated that APP-CT105 causes death of differentiated PC12 cells and cultured rat cortical neurons (Kim and Suh [1996] J. Neurochem. 67:1172-1182) and induces strong inward currents in Xenopus oocyte (Fraser et al., [1996] J. Neurochem. 66:2034-2040). In the present study, to investigate which domain of APP-CT105 is responsible for the neurotoxicity, we have made deletion mutants of APP-CT105 without Abeta and transmembrane domain (TM) or without NPTY domain, a putative endocytosis signaling sequence, using the PCR-amplified strategy and the recombinant GST-fusion protein strategy. The effect on cell survival of the deletion mutants of APP-CT105 (8 microM) was then determined by the LDH and MTT assay. We found that C-terminal fragment without NPTY significantly causes cell death in NGF-differentiated PC12 cells and cultured rat cortical neurons. This finding suggests that NPTY may not play an important role in APP-CT105 mediated neurotoxicity. We found, however, that C-terminal fragment without Abeta and TM significantly induces neuronal cell death. Our results suggest that in addition to Abeta, C-terminal fragment of APP without Abeta and TM domain itself may also participate in the neuronal degeneration in AD.
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PMID:APP carboxyl-terminal fragment without or with abeta domain equally induces cytotoxicity in differentiated PC12 cells and cortical neurons. 1079 60

The nucleotide sequence of hiC12, isolated as a cDNA clone of hardening-induced Chlorella (hiC) genes, was identified. The clone encodes a late embryogenesis abundant (LEA) protein having six repeats of a 11-mer amino acid motif, although in a slightly imperfect form. To overexpress the hiC61) and hiC12 genes, their coding regions were PCR amplified and subcloned into a pGEX-1lambdaT vector. The HIC6 and HIC12 proteins were expressed as GST fusion proteins in E. coli, then purified. The two HIC proteins were found to be effective in protecting a freeze-labile enzyme, LDH, against freeze-inactivation. On a molar concentration basis, they were about 3.1 x 10(6) times more effective in protecting LDH than sucrose and as effective as BSA. Cryoprotection tests with five kinds of chain-shortened polypeptides, synthesized based on the 11-mer amino acid motif of the HIC6 protein showed that the cryoprotective activity decreased with a decrease in the repeating units of the 11-mer motif. In fact, cryoprotective activities of three kinds of single 11-mer amino acids were very low even at high concentrations. All the results suggested that the sufficiently repeated 11-mer motif is required for the cryoprotective activities of Chlorella LEA proteins.
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PMID:Cryoprotective activities of group 3 late embryogenesis abundant proteins from Chlorella vulgaris C-27. 1099 52

The objective of this study was to investigate the effect of the active principles in garlic-- diallyl sulfide (DAS) and diallyl disulfide (DADS)--on aflatoxin B(1) (AFB(1))-induced DNA damage in primary rat hepatocytes. Primary rat hepatocytes, induced with DNA damage using 10 microM AFB(1) were used as an experimental model. According to the results of LDH leakage, 0.5 and 2 mM of DAS or 0.5 and 1 mM of DADS significantly increased the viability of hepatocytes compared with the AFB(1) controls after 4, 8 and 24 h treatment (P<0.05). According to the results of unscheduled DNA synthesis (UDS) test, 0.5 and 2 mM of DAS or 0.5 and 1 mM of DADS could significantly decrease the DNA damage induced by AFB(1) (P<0.05). Furthermore, 0.5 and 2 mM DAS or 0.5 and 1 mM DADS could increase the glutathione S-transferase (GST) and glutathione peroxidase (GPx) activities as compared with the AFB(1) controls after 24 h treatment (P<0.05). Results of immunoblot analysis of cytosolic GST isoenzyme indicate that the levels of GST isoform Ya, Yb2 and Yc were markedly increased after treatment with 0.5 and 2 mM DAS or 0.5 and 1 mM DADS compared with the AFB(1) control. These results indicate that 0.5 and 2 mM DAS or 0.5 and 1 mM DADS might protect hepatocytes from AFB(1)-induced DNA damage via increasing the activities of GST and GPx.
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PMID:Effect of diallyl sulfide and diallyl disulfide, the active principles of garlic, on the aflatoxin B(1)-induced DNA damage in primary rat hepatocytes. 1139 56

Understanding the response of tumors to ionizing radiation might potentially lead to improvement in tumor control and patient morbidity. Since the antioxidant status is likely to be linked to radioresponse, its modulation needs to be examined. Therefore, Swiss albino male mice (7-8 weeks old) with Ehrlich solid tumors were irradiated with different doses of gamma rays (0-9 Gy) at a dose rate of 0.0153 Gy/s; and enzymes involved in antioxidant functions were determined in the tumors. Radiation effects in terms of oxidative damage, LDH, nitric oxide and DNA fragmentation were also examined. In tumors, the specific activity of SOD was increased with dose but declined 6 Gy onwards. GST, DTD and GSH showed an almost progressive increase. These enhanced activities might have resulted from the increased protein expression. This possibility was supported by the Western Blot analysis for GST protein. These changes might be closely linked to the radiation-induced oxidative stress as reflected by the enhanced levels of peroxidative damage, DNA fragmentation, LDH activity and nitric oxide levels. These findings may have relevance to radiation therapy of cancer as the elevated antioxidant status of irradiated tumors is likely to limit the effectiveness of radiation dose and adversely affect the therapeutic gain.
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PMID:Radiation induced oxidative stress: I. Studies in Ehrlich solid tumor in mice. 1168 24

Retroprocessed pseudogenes, calmodulin II (psi1, psi2, and psi3 CALMII), psi alpha-tubulin, pi-glutathione S-transferase (psi pi-GST) from rat, lactic acid dehydrogenase (psi LDH) from mouse, and heat shock protein 60 chaperonin (psi HSP60) from Chinese hamster, were examined for their presence in these species by polymerase chain reaction (PCR). Pseudogenes of these murine rodents were detected by PCR only in those species in which the genes were originally identified, suggesting that the selected pseudogene of one species arose too recently to be detected in the genomes of the other rodent species. The calculated ages of the rodent pseudogenes ranged from 1.7 Myr (psi alpha-tubulin) to 7.5 Myr (psi3 CALMII) when employing a homologous functional gene of the taxon as a reference in the relative rate test with the mouse or rat as the outgroup. Given the high rate of divergence of the genes of rodents relative to other species, selection of an outgroup with similar mutation rates seems warranted. To justify further the conclusion that the selected pseudogenes were indeed retroprocessed after these three taxa diverged, the presence of the pseudogenes in the genome of different rat species was examined. The existence of psi3 CALMII and psi alpha-tubulin pseudogenes of Rattus norvegicus among species belonging to Rattus sensu stricto is evidence for the common ancestry of this group.
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PMID:Age and detection of retroprocessed pseudogenes in murine rodents. 1173 3


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