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)

As many as 160 patients with acute virus hepatitis B (AVHB) were examined over time. Spectroscopy was used to study the activity of glucose-6-phosphate dehydrogenase (G-6-PDH), glutathione peroxidase-1 (GP1), glutathione peroxidase-2 (GP2), glutathione reductase (GR), glutathione transferase (GT) and to measure the concentration of reduced glutathione (GSH) in the blood serum and in red blood cells. Within the first days of the icteric period, the activity of all the enzymes rose, followed by reduction of the activity of G-6-PDH, GP1, GP2, GR and the concentration of GSH at the height of the disease. The GT activity remained high throughout the entire disease period.
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PMID:[The functioning of the glutathione system in patients with acute viral hepatitis B]. 233 29

In a chronic study by the National Toxicology Program (NTP), dimethyl hydrogen phosphite (DMHP) caused neoplastic and nonneoplastic changes in the lungs and forestomach of F344/N rats following gavage administration for 2 years. The current investigation was designed to study the effect of a short-term exposure on a series of biochemical systems in target and nontarget tissues which may be involved in the metabolism and/or the manifestation of DMHP toxicity. Rats were treated daily with a dose similar to that used in the NTP study (200 mg/kg) for 4, 5, or 6 weeks. Two groups of animals were also treated for 4 weeks and then treatment was discontinued and the rats were allowed to recover for 1 or 2 weeks. An equal number of animals was treated similarly with the vehicle and used as control. The microsomal and soluble fractions were separated from liver, lungs, kidneys, forestomach, and glandular stomach from the 6-week treatment group. Another group of rats treated for 6 weeks was prepared for pathology examination of the lungs, forestomach, and glandular stomach. There was a significant increase in the weight of the forestomach of rats treated for 4, 5, or 6 weeks relative to control animals, while no significant difference was observed in the weight of liver, lungs, kidneys, and glandular stomach. The forestomach weight of rats treated for 4 weeks returned to the control value after 1 week of recovery. Microscopic examination of the forestomach of rats treated for 6 weeks revealed a thickened stratified squamous epithelium characterized by hyperplasia, hyperkeratosis, and subepithelial inflammation and edema. There were no microscopic changes in the lungs or glandular stomach of animals treated for 6 weeks. The activity of angiotensin converting enzyme in the serum of rats treated for 4, 5, or 6 weeks was significantly increased over that of control animals. The activity of this enzyme returned to near levels seen in the control animals after 1 week of recovery following 4 weeks of treatment. No treatment-related effect was observed in the activities of the microsomal p-nitroanisole demethylase, soluble glutathione S-transferase, and soluble superoxide dismutase in the five tissues studied. There was a significant increase in the level of nonprotein soluble sulfhydryls in the forestomach but in no other tissue of rats treated for 6 weeks. Also the activity of soluble carboxylesterase was significantly reduced in the lungs and forestomach, but not in any other tissue of the 6-week-treated rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathological and biochemical effects of dimethyl hydrogen phosphite in Fischer 344 rats. 283 31

The acinar distribution of glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G-6-PDH) was examined by analyzing periportal (p.p.) and perivenous (p.v.) rat hepatocytes selectively isolated by the digitonin-collagenase perfusion. The cytosolic GST activity was higher in p.v. cells, but the microsomal GST and cytosolic GR were found to be evenly distributed in the acinus. In contrast, the activity of both the Se-dependent GPx and the microsomal (Se-independent) GPx, as well as G-6-PDH, was much lower in the p.v. than in the p.p. cells. The heterogeneous distribution of GST, GPx and G-6-PDH was confirmed by analyzing liver perfusion effluents collected after ante- or retrograde digitonin infusion. The relatively low activities of GPx and G-6-PDH in the p.v. cells could partly explain the susceptibility of this region to chemical injury.
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PMID:Acinar distribution of glutathione-dependent detoxifying enzymes. Low glutathione peroxidase activity in perivenous hepatocytes. 359 5

Histological effects of ethanol on the kidney were published in our previous report. In the present paper, results of the following measurement will be reported: contents of ethanol and related substances in the urine, both free and bound types, collected during the periods from 30 minutes to 11 hours after ethanol administration to rats, and ACE, alpha-GST, LPO, 25(OH)-D3, 1 alpha-25(OH)2-D3, 24, 25(OH)2-D3 in the serum of rats which had ethanol every day for a month. These will be reported together with histological observation of the kidney excised immediately after the blood sample was collected. The measurement of free and bound types ethanol, acetaldehyde, acetone and methanol in the urine was made up to 11 hours after administration of 4 g/kg b.w./day, p.o. and its results showed the highest contents at 9 hours after the administration. Bound type acetic acid showed the high contents at both 90 minutes and 9 hours after the administration. In 11 hours free type ethanol and acetaldehyde recovered their pre-administration value but as to the bound type only acetic acid recovered it. In the serum of the rats which were ethanol 4 g/kg b.w./day, oral administrated for a mouth, ACE showed significantly high value and 1 alpha, 25(OH)2-D3 and 24, 25(OH)2-D3 showed significantly low value relative to the control. Also alpha-GST showed a low value. In the kidney of the same rats the following changes were observed: swelling of glomerulus, thickening of basement membrane of glomerulus, PAS positive deposits in glomerulus, proliferation of mesangial cell, proliferation of juxtaglomenular cell, dilation of tubular lumen, swelling of tubular epithelial cell, its falling, hyaline droplet in tubular epithelial cell, cell infiltration to interstitial tissue, and basophilic tubule. There was not only difference between findings in the control and those in the liver and the brain of the rats which showed changes above-mentioned. As described above, changes were seen in the renal tissue caused by ethanol administration and in this connection changes in indices related to renal function were observed, too. Furthermore, urinary ethanol and related substances, not only free type but also bound type, that went through the kidney were observed for a long period time. The bound type, in particular, was observed for longer duration and hence effects of ethanol on the kidney were surely assumed. Presently longer term experiments are proceeding and other indices connected with renal functions are being studied.
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PMID:[Effect of long-term ethanol administration (2). Free type and bound type ethanol and related substances contents of the urine from ethanol administrated rats, indices in the serum, and renal tissues]. 910 39

In 14 patients (4 males and 10 females) with systemic hypertension plasma and erythrocyte lipid peroxides, plasma and erythrocyte catalase activity, plasma glutathione S-transferase (GST) activity, blood reduced glutathione (GSH) content and erythrocyte oxidant stress were investigated. All parameters were performed after clinical examination and then the patients were assigned to receive ACE inhibitor therapy, captopril (25-50 mg given twice per day) or enalapril (10-40 mg given twice per day). After six months the determination of lipid peroxides and antioxidative factors was repeated. At the beginning of the study both treated groups showed significantly higher plasma lipid peroxides compared to the control group. Both used ACE inhibitors produced significant decrease of plasma lipid peroxides after six months. Blood GSH content was also significantly higher in both patient groups before the treatment compared to the controls. Neither captopril nor enalapril produced any significant effect on GSH. Initial values of plasma GST activity in the patients were similar to the control group and did not significantly change after six month treatment. The patients assigned to receive enalapril showed significantly enhanced initial plasma catalase activity according to the controls. After six months treatment both ACE inhibitors significantly decreased plasma catalase activity. Erythrocyte lipid peroxides, erythrocyte catalase activity and oxidant stress of erythrocytes in both groups studied neither differ significantly at initial time of investigation according to the control group nor during or after six month treatment.
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PMID:Changes of lipid peroxides and antioxidative factors levels in blood of patients treated with ACE inhibitors. 912 91

Site-specific proteases play critical roles in regulating many cellular processes. To identify novel site-specific proteases, their regulators, and substrates, we have designed a general reporter system in Saccharomyces cerevisiae in which a transcription factor is linked to the intracellular domain of a transmembrane protein by protease cleavage sites. Here, we explore the efficacy of this approach by using caspases, a family of aspartate-specific cysteine proteases, as a model. Introduction of an active caspase into cells that express a caspase-cleavable reporter results in the release of the transcription factor from the membrane and subsequent activation of a nuclear reporter. We show that known caspases activate the reporter, that an activator of caspase activity stimulates reporter activation in the presence of an otherwise inactive caspase, and that caspase inhibitors suppress caspase-dependent reporter activity. We also find that, although low or moderate levels of active caspase expression do not compromise yeast cell growth, higher level expression leads to lethality. We have exploited this observation to isolate clones from a Drosophila embryo cDNA library that block DCP-1 caspase-dependent yeast cell death. Among these clones, we identified the known cell death inhibitor DIAP1. We showed, by using bacterially synthesized proteins, that glutathione S-transferase-DIAP1 directly inhibits DCP-1 caspase activity but that it had minimal effect on the activity of a predomainless version of a second Drosophila caspase, drICE.
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PMID:A cloning method to identify caspases and their regulators in yeast: identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP-1. 1007 6

Many of the discoveries of multidrug resistance (MDR) have resulted from studies using drug-resistant cultured tumor cell lines as experimental models. To date, there has been no report on the detailed characterization of such a cell line from renal cell carcinoma (RCC). By long-term exposure of an established RCC (RCC8701) to increasing concentrations of adriamycin, we established a series of subcultures that were considerably more resistant to the cytotoxic effect of this drug. Biological morphology and cell cycles were analyzed by morphometry and flow cytometry. The chemoresistance index of cells were measured by methyl tetrazolium assay. For evaluation of the expression of MDR-related protein (MRP), mdr-1, glutathione transferase (GST-pi), and topoisomerase II mRNAs, the reverse transcription-polymerase chain reaction was used. Membranous expression of mdr-1-related p-glycoprotein was analyzed by immunofluorescence cytometry. The intracellular content of both glutathione (GSH) and glucose-6-phosphate dehydrogenase (G-6-PDH) were measured using a capillary electrophoresis method. Compared with parent cells, the resistant sublines had a slower growth rate and lower confluent density. They were smaller and mixed with giant cells in different sizes and with different numbers of nucleoli. Flow cytometric analyses showed that resistant cells had a greater percentage of cells in the G2/M phase. The resistant cells, RCC8701/ADR800, were 122 times more resistant to adriamycin and 238 times more resistant to epirubicin than the parent cells. The resistant cells also demonstrated cross-resistance to cisplatin and 5-fluorouracil. In addition to MRP, the contents of mRNA coding for mdr-1, GST-pi, and topoisomerase II in the MDR sublines were higher than in the native cell line. A higher content of cytoplasmic GSH and G-6-PDH were found in the resistant cells; however, the expression of the MDR-related membranous glycoprotein, p-glycoprotein, was not raised. The adriamycin-induced MDR sublines may be used as an experimental system for the search of a means to overcome drug resistance and elucidate possible mechanisms of acquired MDR involved in human renal cancer.
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PMID:Establishment and characterization of renal cell carcinoma cell lines with multidrug resistance. 1085 Jun 29

A comparative study has been performed on populations of Unionidae from the Lake Suszek and Brda river situated in the centre of Tucholski Landscape Park, around which there are no factories and the Pilica river--affected by the influence of the nearby town agglomeration. Mussels collected from Suszek were also treated (72 h) with various concentrations of dichlorophenol (DCP; 0.1, 0.15, 0.2 ppm) and paraquat (PQ; 1, 5, 10 ppm) in laboratory conditions (aquarium). The activities of glutathione S-transferase (GST) and cytochrome P450 monooxygenase system (NAD(P)H ferricyanide reductase, NAD(P)H cytochrome c reductase), cytochrome P450 content and b(5) in microsomal and cytosolic fractions of digestive gland were investigated. The differences in enzyme activities between groups of mussels, which were exposed to various concentrations of chemical pollutants, as well as the dependence on geographical distribution in Poland, were observed. In experiments with DCP the dose-dependent increase in GST activity was found, but no changes after PQ treatment were observed. Results, in experiments with DCP and PQ, have varied from no change to increase or decrease in the measured monooxygenase activities and cytochrome P450 content. Increases have been recorded in two cases (NADPH ferricyanide reductase and cytochrome P450) after exposure to DCP and in the case of NADH ferricyanide reductase following the exposure to PQ. NAD(P)H cytochrome c reductase activity and content of P450 decreased considerably in 5 and 10 ppm PQ-treated mussels. Thus, the treatment with DCP and PQ in water changed the properties of the mussels digestive gland cytochrome P450 monooxygenase system. These changes may be used as a bioindicator, at the molecular level, of exposure to those xenobiotics not only in controlled experiments (aquaria) but also in the natural environment.
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PMID:Comparative study of the xenobiotic metabolising system in the digestive gland of the bivalve molluscs in different aquatic ecosystems and in aquaria experiments. 1229 71

DCP has been utilized as a soil fumigant for more than 45 yr for the control for parasitic plant nematodes. Injected into soil before planting of crops, the instability of DCP in soil and water and its volatility dictate the principal route of human exposure that may occur, inhalation. Extensive data have been accumulated on the toxicity and metabolism of DCP. DCP is moderately toxic via oral or inhalation exposure, is irritating to the skin and eyes, and has potential to produce skin sensitization. It is rapidly and extensively metabolized. It has a half-life in the blood of rats and humans of only 3-7 min and < 10 min, respectively. Rats and mice excrete approximately 80% of even relatively high oral dosages within 24 hr, primarily as breakdown products of a glutathione conjugate or as carbon dioxide. These products reflect the primary routes of metabolism of DCP, via GSH-conjugative and hydrolytic pathways. An additional pathway based upon the epoxidation of DCP has also been proposed, but this does not appear to occur to any toxicologically significant degree in the presence of normally occurring GSTs. Direct evidence of the latter pathway is only been obtained at dosages of DCP in excess of the reported LD50. Humans also appear to rapidly metabolize DCP and excrete its metabolites. Subchronic toxicity studies of relatively pure DCP in rats and mice via oral or inhalation routes have resulted in portal-of-entry tissue effects that reflect the irritant properties of this chemical to nasal and gastric mucosa. At higher exposure levels in mice, however, toxicity was also identified in a remote tissue, the urinary bladder. Toxicity in dogs ingesting DCP was limited to the formation of a regenerative hypochromic, microcytic anemia. No teratological or reproductive effects were observed in rats or rabbits inhaling DCP vapors. Nonneoplastic changes from chronic dosing of DCP were generally similar to those observed in subchronic studies. Somewhat variable responses, however, have been observed for neoplastic effects, depending on the DCP formulation, route, and species used. Inhalation of a recent formulation increased the benign tumor incidence in the lungs of male mice (only) while ingestion of similar test material by rats and mice resulted in a low incidence of benign liver tumors in rats (only). In contrast, an older formulation containing Epi as a stabilizing agent administered to rats and mice via bolus oral dosing induced a number of malignant or benign tumors: in the forestomach and liver in rats and the forestomach, lung, and urinary bladder in mice. An equally complicated database has accumulated for DCP in vitro and in vivo genotoxicity testing. Genotoxicity has been reported in in vitro assays; however, confounding factors such as low-purity formulations, use of a genotoxic stabilizer, or generation of reactive impurities during attempts to purify test material have complicated interpretation. DCP appears to lack direct DNA reactivity, and a general trend toward decreasing activity with increasing complexity of the assay system and the presence of GST is evident. The weight-of-evidence evaluation of the genotoxicity data base suggests a lack of genotoxicity in vivo. Clearly definable treatment-related effects of DCP suggesting a plausible nongenotoxic mechanism of tumorigenic action, for example, enhanced cell proliferation, have not been in evidence in target tissues of treated animals. Thus, the specific mode of tumorigenesis of DCP in test animals remains to be elucidated but appears to involve a non-DNA-reactive mechanism. In conclusion, DCP-based soil fumigants have maintained an important role in agricultural despite the structural similarity of DCP to known genotoxic carcinogens and its own activity in in vitro genotoxicity assays. This role results from a combination of its use on soils before the planting of crops, its limited environmental half-life, rapid metabolism by animals via GSH conjugation and catabolism to CO2, lack of genotoxicity in in vivo assays, and an extensive toxicological database in animals, including several oncogenicity bioassays. These data, when combined with occupational and environmental exposure information, have provided a scientifically sound basis for the continued safe use of DCP-containing products.
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PMID:Mammalian toxicity of 1,3-dichloropropene. 1288 26

There were few reports on the antioxidant response of aquatic organisms exposed to 2,4-dichlorophenol (2,4-DCP). This research explored the hepatic antioxidant responses of fish to long-term exposure of 2,4-DCP for the first time. Freshwater fish Carassius auratus were chosen as experimental animals. The fish were exposed to six different concentrations of 2,4-DCP (0.005-1.0 mg/l) for 40 days and then liver tissues were separated for determination. As shown from the results, 40 days afterwards, the activities of catalase (CAT) and selenium-dependent glutathione peroxidase (Se-GPx) and the content of oxidized glutathione (GSSG) were induced significantly on the whole compared to control group; superoxide dismutase (SOD) responded to 2,4-DCP exposure at only 0.005 mg/l; the content of reduced glutathione (GSH) was suppressed continuously except Group 7; the activity of glutathione reductase was inhibited initially and then restored to control level from Group 4 on; glutathione S-transferase had only slight responses in Groups 3 and 4. Total glutathione (tGSH) and GSH/GSSG ratio were also calculated to analyze the occurrence of oxidative stress. Besides, good dose-effect relations, which cover most of the exposure concentration range, were found between 2,4-DCP level and CAT activity, GSSG content, Se-GPx activity, respectively. In conclusion, SOD and Se-GPx may be potential early biomarkers of 2,4-DCP contamination in aquatic ecosystems, and further studies will be necessary.
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PMID:Effects of chronic exposure of 2,4-dichlorophenol on the antioxidant system in liver of freshwater fish Carassius auratus. 1476 89


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