Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We studied the acute effects of cigarette smoke condensate (CSC), H2O2, and tumor necrosis factor (TNF)-alpha on the glutathione (GSH) redox system in a human type II epithelial cell line (A549) in vitro. CSC, in vitro and in vivo after intratracheal instillation of CSC in the rat, produced a depletion of intracellular soluble GSH, concomitant with GSH-conjugate formation, without significant elevation of oxidized GSH (GSSG), protein-GSH mixed disulfides (PrSSG), nor any GSH efflux from the cells. By contrast, H2O2 (500 microM) after 5-min exposure to A549 cells caused significant depletion of intracellular GSH associated with an efflux of GSSG and a significant increase in the formation of PrSSG. TNF-alpha, in concentrations of 100 U/ml and 1,000 U/ml, produced a significant depletion of GSH in A549 cells after 4- and 24-h exposure, with an associated elevation of GSSG. The activities of glutathione peroxidase, gamma-glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase were significantly decreased in epithelial cells and in rat lungs after CSC exposure, without change in glutathione S-transferase and glutathione reductase activities. By contrast, H2O2 and TNF-alpha did not alter these enzyme activities in epithelial cells. Thus GSH depletion and alteration in enzyme activities in alveolar epithelial cells by CSC, H2O2, and TNF-alpha occur by different mechanisms.
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PMID:Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress. 757 60

Male weanling rats were fed diets containing either adequate (6.2 mg/kg) or deficient (0.82 mg/kg) quantities of copper for 35 days. Six rats from each group (n = 12) were then injected with streptozotocin to induce diabetes. Rats were killed after a further 16 days and tissues removed for the analysis of the copper level and antioxidant enzyme activities. Diabetes resulted in increased cardiac catalase, glutathione S-transferase (GST), copper-zinc superoxide dismutase and manganese superoxide dismutase activities. Renal catalase levels were decreased in diabetes, while glucose-6-phosphate dehydrogenase activity (G6PDH) was increased. Diabetes significantly decreased the activities of hepatic GST and G6PDH. The combination of diabetes and copper deficiency resulted in increased levels of hepatic GST, glutathione peroxidase and glutathione reductase. Hepatic and renal tissue copper levels were also increased in diabetes, apparently improving copper status in the copper-deficient rats. Alterations of antioxidant enzyme activities in diabetes were suggestive of increased oxidant stress, especially in cardiac tissue.
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PMID:Effects of copper deficiency and experimental diabetes on tissue antioxidant enzyme levels in rats. 771 Feb 61

Preneoplastic and neoplastic liver cell lesions, induced by EHEN (N-ethyl-N-hydroxyethylnitrosamine) in rats, were investigated to establish the numbers of simultaneously expressed altered enzyme phenotypes within the lesion cells. The lesions were divided into 5 classes on the basis of altered expression in one or more of the following 5 enzymes: glutathione S-transferase placental form, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, adenosine triphosphatase, and gamma-glutamyl transpeptidase. Class 1 lesions contained cells expressing one altered enzyme. Similarly, class 2, 3, 4 and 5 lesions had cells simultaneously expressing 2, 3, 4, and 5 enzyme alterations, respectively. Four histopathological categories of lesions, ACF (altered cell foci) (274 lesions), HN (hyperplastic nodules) (47 lesions), HCC (hepatocellular carcinomas) (99 lesions) and THC (transplanted hepatocellular carcinomas) (5 lesions) were studied. Proliferation potential was assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. The distribution profiles of classes 1 to 5 showed a clear reciprocal change from low class (1 to 2 enzymes) predominance in ACF to high class (4 to 5 enzymes) predominance in HN. Increase of BrdU labeling indices was clearly correlated with progression from HN to HCC. Only a small population of class 5 ACF showed a high BrdU labeling index, indicating particular potential for further development. Thus, the stages of EHEN-induced neoplasia were found to be characterized by gradual increase in the number of altered enzyme phenotypes, with acquisition of proliferative potential being associated with further progression towards malignant conversion.
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PMID:Number of simultaneously expressed enzyme alterations correlates with progression of N-ethyl-N-hydroxyethylnitrosamine-induced hepatocarcinogenesis in rats. 790 86

To get a better insight into the pathophysiology of the nasal changes induced by formaldehyde-ozone mixtures, a 3-day inhalation study was carried out in rats, using intermittent exposure to formaldehyde (3.6 ppm) and ozone (0.4 ppm) alone or in combination and focusing on biochemical and histopathological changes in rat nasal respiratory epithelium. Formaldehyde dehydrogenase, glutathione S-transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities in this epithelium were not affected by the individual compounds. However, combined exposure to formaldehyde and ozone resulted in slightly decreased activities of these enzymes. Formaldehyde was found to induce rhinitis, degeneration, frank necrosis, hyperplasia and squamous metaplasia of the ciliated and non-ciliated nasal respiratory epithelium, while ozone induced disarrangement, flattening and slight basal cell hyperplasia of the non-ciliated cuboidal epithelium accompanied by influx of neutrophils. Proliferating cell nuclear antigen (PCNA) expression was elevated not only in nasal areas showing ozone-induced histopathological changes but also in the otherwise normal-appearing epithelium of the nasal septum. No interactive effects were found with respect to proliferative response of the nasal respiratory epithelium after exposure to the formaldehyde-ozone mixture. The present study did not provide evidence of a major role of glutathione and glutathione-dependent enzymes in the pathogenesis of nasal lesions induced by formaldehyde and/or ozone, demonstrated the potential of ozone to affect the mucociliary epithelium lining the nasal septum, and suggested that PCNA expression is a sensitive tool for detection of early effects of respiratory irritants.
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PMID:Biochemical and histopathological changes in nasal epithelium of rats after 3-day intermittent exposure to formaldehyde and ozone alone or in combination. 791 Dec 63

The anti-oxidant metabolism was studied at different times after sub-culture in 2 colon cell lines previously characterized for their growth and differentiation properties. The HT29 cell line is mainly composed of proliferative and undifferentiative cells, while the derived 5-fluorouracil (FUra)-adapted cells undergo growth-dependent differentiation, which is complete at post-confluence. In the 2 cell lines, all the anti-oxidant parameters studied appeared to be related to proliferation, with increased activity of superoxide dismutase (SOD) 1 and 2, catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GSR), and glutathione transferase (GST), and decreased glucose-6-phosphate dehydrogenase (G6PD) activity and glutathione content, in parallel with slowing down of proliferation. At post-confluence, these metabolic parameters remained stable, except for GPX activity, which continued to increase, and CAT activity, which decreased. The amounts of SOD1, SOD2 and CAT immunoreactive proteins, estimated by Western blotting, appeared to be correlated to their respective enzymatic activities. SOD1, CAT and GST activity and glutathione content, which remained at similar levels in the 2 cell lines for all times studied, appeared unrelated to the differentiation process. GSR and GPX activity, which was lower in FUra-adapted than in parental cells only at post-confluence, could be considered as markers of differentiated cells. The higher SOD2 and lower G6PD activity observed in FUra-resistant cell in comparison with parental cells at all times after sub-culture could be characteristic both of differentiative and of differentiated cells. Interestingly, cytogenetics have previously indicated that deletions of the long arm of chromosome 6, which carry the gene for SOD2, were frequently observed in parental but not in FUra-adapted cells. These results demonstrate that modifications of the anti-oxidant metabolism occur in relation with proliferation and differentiation, and suggest a particular role for SOD2 in these cellular processes.
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PMID:Modifications of the anti-oxidant metabolism during proliferation and differentiation of colon tumor cell lines. 798 27

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


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