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)

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

Feeding diets depleted of vitamin E and Se to cattle can induce a disease known as nutritional degenerative myopathy. It is believed that an increased peroxidative challenge in muscle is involved in the pathogenesis of this disease. A number of species can up-regulate the activity of some antioxidant enzymes, including glutathione reductase (EC 1.6.4.2), glutathione transferase (EC 2.5.1.18), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), catalase (EC 1.11.1.6), and superoxide dismutase (EC 1.15.1.1), in an attempt to mitigate the effects of a peroxidative challenge. A 2 x 2 factorial study was set up to examine possible changes in the activities of these antioxidant enzymes in muscles of ruminant calves fed on diets low in either vitamin E or Se. Four groups of four calves each were fed on a basal diet of NaOH-treated barley which was supplemented with alpha-tocopherol or Se or both for a total of 50 weeks. Calves fed on diets depleted of vitamin E, but not those fed on diets low in Se, developed subclinical myopathy, as judged by increases in the activity of plasma creatinine kinase (EC 2.7.3.2), and had increased muscle concentrations of two indices of lipid peroxidation, namely thiobarbituric acid-reactive substances, with and without ascorbate activation. Feeding diets depleted of vitamin E and diets low in Se both increased muscle activities of glucose-6-phosphate dehydrogenase in heart, biceps and supraspinatus. This change may have occurred in an attempt to maintain intracellular pools of reduced glutathione. No other changes in antioxidant enzyme activity were observed.
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PMID:Antioxidant enzyme activity in the muscles of calves depleted of vitamin E or selenium or both. 826 Apr 86

Glutathione levels and several glutathione-linked enzyme activities have been variably correlated with cisplatin chemosensitivity in cultured neoplastic cells. In order to determine the relative contribution of the glutathione-linked enzymes towards mediating inherent cisplatin resistance in cancer cells, we have measured the chemosensitivity to cisplatin, glutathione levels and activities of glutathione S-transferase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in 8 cultured human small cell lung cancer (SCLC) cell lines with widely differing cisplatin sensitivities. Of these parameters, only glutathione S-transferase activity correlated with degree of cisplatin resistance in a linear fashion.
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PMID:Glutathione and glutathione linked enzymes in human small cell lung cancer cell lines. 829 21

The in vivo toxicity of ozonides, possible intermediates in ozone-induced toxicity, was investigated. Methyl linoleate ozonide (MLO) (0.07 mmol/100 g body wt.), a model fatty acid ozonide, was administered to female Wistar rats either intravenously or intraperitoneally. After 24 h the rats were killed and the effects were examined. MLO was found to be toxic only after intravenous administration. The major effects were observed in the lungs. The lungs became enlarged from edema and showed severe hemorrhages. Further, total thiol was depleted in serum and lung tissue, accompanied with a significant decrease in activity of glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and glutathione S-transferase. The vitamin E levels in serum and lung tissue were reduced. The malondialdehyde (MDA) concentrations in serum and lung tissue were elevated suggesting that in vivo oxidation had occurred. On intraperitoneal administration of MLO, no effects on enzyme activities, thiol and vitamin E content in lung tissue were observed. In serum, however, as on intravenous administration, an increase of the MDA levels and decreases of total thiol and vitamin E levels were found. In view of the route of administration it is to be expected that the ozonide is partly cleared by the liver, and the ozonide and its potentially toxic products are further detoxicated by vitamin E and thiols in serum before they reach the lung. The above data show that the main target organ for ozonides is the lung, and that the effects caused by MLO in vivo are in many respects similar to the effects found after acute ozone exposure. This supports the working hypothesis that ozonides may play a role in ozone-induced lung toxicity.
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PMID:Toxicity of methyl linoleate ozonide in the rat. 832 99

The activities of several enzymes involved in the antioxidant system of the cell were studied in parallel to cytogenetic alterations at various times after SV40 infection and transformation of human fibroblasts. At early passages after SV40 infection, glutathione reductase (GSR), glutathione peroxidase (GPX), glutathione transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD) activities were decreased. This, associated with the low superoxide dismutase (SOD) and catalase activities previously noticed in these cells, suggested that they are in a highly pro-oxidant status. Although chromosomes carrying the genes encoding these enzymes are frequently underrepresented, there is no direct relationship between the number of chromosomes and enzyme activities. Except for GPX, all the activities tend to increase in established cell lines reaching levels comparable to those of non-transformed fibroblasts. The late increase of G6PD activity may correlate with the frequent duplication of the early replicating X. GSR seems to correlate with G6PD activity and GPX to SOD total activity. The most striking alterations affect mitochondrial and peroxisomal enzymes activities: SOD, GPX and catalase.
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PMID:Alterations of the glutathione cycle enzymes during and after SV40-transformation of human fibroblasts. 838 Oct 54

The enzymes acetylcholinesterase, glutathione S-transferase (GST), glucose 6-phosphate dehydrogenase (G6PD), and general esterases were assayed in four strains of Aedes aegypti mosquitoes aged between 1 and 30 days. Microtitre plate methods were used to assay activity in the homogenates of individual mosquitoes. The levels of GST and G6PD declined with the age of the mosquitoes, while the activity for the other enzymes remained constant. Soluble protein content was also found to decline with mosquito age in all the strains. Insecticide bioassays showed that two strains (Trinidad and Virtudes) of Ae. aegypti were resistant to DDT, deltamethrin and malathion, whereas two other strains (Bangkok and Indian) were susceptible to all four classes of insecticides tested. Higher esterase activity levels in the resistant compared to the susceptible strains were assumed to be the cause of organophosphate resistance. The combination of DDT and deltamethrin resistance in two strains with normal GST and G6PD characteristics suggests that a kdr-type nerve insensitivity mechanism may be involved.
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PMID:Changes in enzyme titres with age in four geographical strains of Aedes aegypti and their association with insecticide resistance. 843 83

As demonstrated previously, liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-diabetic rats are altered in various respects. The hepatocytes in these acini store glycogen and/or fat, and they show an increase in proliferation as well as in apoptotic activity. Thus, they are phenotypically similar to carcinogen-induced preneoplastic liver foci (glycogen-storing foci and sometimes also mixed cell foci). By means of catalytic enzyme histochemistry or immunohistochemistry, we investigated the activity of key enzymes of alternative pathways of carbohydrate metabolism and some additional marker enzymes (well known from studies on preneoplastic hepatic foci) in the altered liver acini surrounding the islet isografts. In addition, the expression of glucose transporter proteins 1 and 2 (GLUT-1 and GLUT-2) were investigated immunohistochemically. The activities of hexokinase, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase were increased, whereas the activities of glycogen phosphorylase, adenylate cyclase, glucose-6-phosphatase, and membrane-bound adenosine triphosphatase were decreased in the altered liver acini. The expression of GLUT-2 was also decreased. GLUT-1 and glutathione S-transferase placental form were not expressed, and the activities of glycogen synthase and gamma-glutamyl-transferase remained unchanged. All changes of the enzyme activities were in line with the well known effects of insulin and resembled alterations characteristic of preneoplastic liver foci observed in different models of hepatocarcinogenesis. It remains to be clarified in long-term experiments whether or not these foci represent preneoplastic lesions and may proceed to neoplasia.
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PMID:Altered liver acini induced in diabetic rats by portal vein islet isografts resemble preneoplastic hepatic foci in their enzymic pattern. 864 65

Microsomal glutathione transferase (GSTm) is activated up to fivefold by incubation with glutathione disulfide (GSSG). The process is reversed by the addition of an NADPH-regenerating system consisting of glutathione reductase and glucose 6-phosphate/glucose-6-phosphate dehydrogenase. By treating the microsomes at different GSH/GSSG ratios a Kox value of 0.047 is found, i.e., 21 times more GSSG than GSH is necessary to produce half-maximal activation. The Kox is independent of the total glutathione concentration, indicating that S-thiolation by GSH rather than interchain or intrachain disulfide bridge formation is responsible for activation. Further evidence for S-thiolation of GSTm comes from SDS-PAGE under nonreducing conditions and Western blotting. Treating microsomes with GSSG or with GSH and t-butyl hydroperoxide or cumene hydroperoxide results in the appearance of a second GSTm band at approximately 17.7 kDa in addition to the native band at 17.3 kDa, the size difference approximately corresponding to the molecular mass of glutathione. The 17.7-kDa band is not seen in the presence of mercaptoethanol. Microsomal preparations from rat livers perfused with t-butyl hydroperoxide or cumene hydroperoxide also contain both GSTm forms. We suggest that under oxidative stress the microsomal GST in the cell can be activated through direct hydroperoxide-mediated S-thiolation of the enzyme with GSH, its reversal occurring via a thiol exchange-mediated dethiolation imposed by the intracellular glutathione redox state.
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PMID:Protein S-thiolation and regulation of microsomal glutathione transferase activity by the glutathione redox couple. 880 37

Ultrastructural, stereological and biochemical alterations in isolated hepatocytes and the permanent fibrocyte-like cell line R1 from rainbow trout (Oncorhynchus mykiss) exposed to 0, 0.2, 2 and 20 mg/l of the phosphorodithioate pesticide disulfoton (Solvirex, O,O-diethyl S-2-ethylthioethyl phosphorodithioate) for up to 5 days were investigated. In both R1 cells and isolated hepatocytes, distinct dose- and time-dependent morphological alterations including diminished amounts of heterochromatin, proliferation of lysosomal elements, dilation and vesiculation of endoplasmic reticulum cisternae, induction of concentric membrane whorls and an increased amount of lipid droplets could be detected at concentrations of > or = 2 mg/l (R1 cells) and > or = 0.2 mg/l disulfoton (hepatocytes). Additional effects in isolated hepatocytes comprised marginalization of heterochromatin, myelin-like structures attached to mitochondrial membranes, formation of ring-shaped mitochondria, proliferation of smooth endoplasmic reticulum, reduction of rough endoplasmic reticulum, induction of ring-shaped Golgi cisternae, glycogen depletion and occurrence of glycogenosomes. Structural changes in isolated hepatocytes could be correlated to suppression of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, alanine aminotransferase, malic enzyme, esterase as well as glutathione S-transferase, but to a stimulation of 7-ethoxycoumarin-O-deethylase and the rate of lipid peroxidation at concentrations > or = 0.01 mg/l disulfoton. Comparison with data from in vivo experiments with rainbow trout indicate the suitability of in vitro techniques for the evaluation of the toxicological potential of a wide range of ecotoxicologically relevant substances.
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PMID:Cytological and biochemical response of R1 cells and isolated hepatocytes from rainbow trout (Oncorhynchus mykiss) to subacute in vitro exposure to disulfoton. 891 71

Two different types of focal preneoplastic lesions, tentatively named Type I and II lesions, were recognized in the liver of rats chronically treated with clofibrate for 104 weeks. Type I lesions were characterized by mostly negative glucose-6-phosphate dehydrogenase (G6PD) activity (6 out of 10, 60%) and positive expression of succinate dehydrogenase (10 out of 10, 100%), in addition to the previously documented complete lack of expression of glutathione S-transferase, placental form (GST-P) and gamma-glutamyl transpeptidase (GGT). Furthermore, most importantly, Type I lesions exhibited a clear decrease in immunohistochemically demonstrated connexin32 (Cx32) spot counts on their hepatocyte membranes, similarly to nitrosamine-induced lesions. In contrast, Type II lesions, mostly small in size and positively expressing GST-P and/or GGT and G6PD, similarly to their previously reported nitrosamine-induced counterparts, did not exhibit a significant decrease in Cx32 count. In addition, spontaneously occurring lesions, again sharing the same enzyme phenotype, did not show a decrease in Cx32. The results indicate that: (i) a clear distinction between the two lesions, with Type I being involved in clofibrate-induced tumors and Type II being more likely to be spontaneous in nature; (ii) a decrease in Cx32 is closely linked to lesion development and possibly stage of progression, irrespective of the enzyme phenotype and the applied carcinogen; (iii) the unaltered condition of Cx32 may suggest a slow growing or non-progressive nature.
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PMID:Decreased connexin32 and a characteristic enzyme phenotype in clofibrate-induced preneoplastic lesions not shared with spontaneously occurring lesions in the rat liver. 896 61


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