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)

This paper presents an analysis of glutathione S-transferase (GST) activity of leukemic cells in 30 patients with acute leukemias and its predictive value for therapy. Blast cells were isolated from peripheral blood or bone marrow before induction therapy using Ficoll density gradient. GST activity was measured according to the spectrophotometric assay based on the use of 1-chloro-2,4-dinitrobenzene as a substrate. The results did not show any significant differences between activities of the enzyme within the different leukemia types according to the French-American-British (FAB) classification. The patients who achieved complete remission demonstrated the lowest value of enzyme activity. The highest enzyme activity was observed in those patients who achieved partial remission and the non-responsive patients presented a GST value within the median of these two groups. Two categories of patients were represented within the non-responsive treatment group. One was resistant to the conventional therapy and in the other death was caused by infectious or hemorrhagic complications. The mean GST activity in these two groups of patients differ greatly. These results suggest that low GST activity of leukemic cells could be a favourable prognostic factor whereas high GST values could help to find out the group of patients who should be further analysed prior to induction therapy.
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PMID:Glutathione S-transferase activity of leukemic cells as a prognostic factor for response to chemotherapy in acute leukemias. 204 80

The effect of dietary cabbage (Brassica oleracea) on the binding of aflatoxin B1 (AFB1) to hepatic DNA and on the activities of liver and intestinal microsomal and cytosolic enzymes was studied in weanling male Fischer 344 rats. Freeze-dried cabbage was fed to rats at a level of 25% in the diet for 21 days, while others received a basal diet. In the cabbage-fed group there was an 87% (P less than 0.01) reduction in the binding of AFB1 to hepatic DNA 2 hr after the ip injection of [3H]AFB1 (3 micrograms/kg). There was also a 41% (P less than 0.05) increase in liver weight expressed relative to body weight. Hepatic and intestinal glutathione S-transferase activities were significantly increased (2.1- and 2.3-fold, respectively) over those in rats fed the basal diet. Hepatic and intestinal microsomal epoxide hydrolase activities were significantly increased (2.6- and 1.4-fold, respectively) over the basal group. Intestinal aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECD) activities were significantly increased (2.3- and 2.5-fold, respectively), over the basal group but dietary cabbage had no significant effect on hepatic AHH or ECD activities.
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PMID:The effects of dietary cabbage on xenobiotic-metabolizing enzymes and the binding of aflatoxin B1 to hepatic DNA in rats. 311 6

Glutathione-depleted hepatocytes, by incubation with diethylmaleate (DEM) or phorone (2,6-dimethyl-2,5-heptadiene-4-one), i.e., substrates of the GSH S-transferases (EC 2.5.1.18), showed rates of gluconeogenesis from various precursors significantly lower than controls; however the rate of glucose synthesis from fructose was similar to that of controls. Isolated hepatocytes from rats pretreated with those substrates 1 h before isolation to deplete hepatic glutathione (GSH) also showed a decrease of the rate of gluconeogenesis from lactate plus pyruvate. Incubation of hepatocytes with L-buthionine sulfoximine, a specific inhibitor of gamma-glutamyl-cysteine synthetase (EC 6.3.2.2), resulted in a decreased rate of gluconeogenesis from lactate plus pyruvate only when GSH values were lower than 1 mumol/g cells. Freeze-clamped livers from GSH-depleted rats showed a higher concentration of malate and glycerol 3-phosphate, indicating that GSH depletion probably affects phosphoenolpyruvate carboxykinase and glycerol-3-phosphate dehydrogenase activities. Several indicators of cell viability, such as lactate dehydrogenase leakage, malondialdehyde accumulation, ATP concentration, or urea synthesis from different precursors, were not affected by GSH depletion under the experimental conditions used here. Besides, the GSH/GSSG ratio remained unchanged in all cases.
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PMID:Effects of glutathione depletion on gluconeogenesis in isolated hepatocytes. 402 24

Blast cells obtained from 104 children with untreated acute lymphoblastic leukaemia were analysed for the expression of P-glycoprotein (P-170) and glutathione S-transfer pi (GST-pi) using immunohistochemistry. Expression of P-170 was detected in 36 of 104 patients (35%) and increased GST-pi was seen in 52 patients (50%). Coexpression of both resistance proteins was observed in 22 leukaemias (21%), whereas no evidence of the resistance markers was found in 38 cases (37%). In patients with P-170-positive leukaemic cells, a significantly lower probability of remaining in first continuous complete remission (CCR) was observed when compared with patients with P-170-negative tumours (P < 0.05). However, only a trend for a more frequent expression of P-170 was found in the leukaemic cells of patients who experienced relapses (P = 0.099). Overexpression of GST-pi was correlated with a higher relapse rate (P = 0.001) and a lower probability of remaining in first CCR (P = 0.01). Expression of P-170 and GST-pi was independent of sex, FAB type, immunological subtype and initial blast cell count. The multivariate analysis indicated that only the expression of P-170 is an unfavourable prognostic factor for children with acute lymphoblastic leukaemia in addition to the prognostic clinical factors.
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PMID:P-glycoprotein and glutathione S-transferase pi in childhood acute lymphoblastic leukaemia. 798 Oct 66

Raffinose family oligosaccharides (RFO) accumulating during seed development are thought to play a role in the desiccation tolerance of seeds. However, the functions of RFO in desiccation tolerance have not been elucidated. Here we examine the functions of RFO in Arabidopsis thaliana plants under drought- and cold-stress conditions, based on the analyses of function and expression of genes involved in RFO biosynthesis. Sugar analysis showed that drought-, high salinity- and cold-treated Arabidopsis plants accumulate a large amount of raffinose and galactinol, but not stachyose. Raffinose and galactinol were not detected in unstressed plants. This suggests that raffinose and galactinol are involved in tolerance to drought, high salinity and cold stresses. Galactinol synthase (GolS) catalyses the first step in the biosynthesis of RFO from UDP-galactose. We identified three stress-responsive GolS genes (AtGolS1, 2 and 3) among seven Arabidopsis GolS genes. AtGolS1 and 2 were induced by drought and high-salinity stresses, but not by cold stress. By contrast, AtGolS3 was induced by cold stress but not by drought or salt stress. All the GST fusion proteins of GST-AtGolS1, 2 and 3 expressed in Escherichia coli had galactinol synthase activities. Overexpression of AtGolS2 in transgenic Arabidopsis caused an increase in endogenous galactinol and raffinose, and showed reduced transpiration from leaves to improve drought tolerance. These results show that stress-inducible galactinol synthase plays a key role in the accumulation of galactinol and raffinose under abiotic stress conditions, and that galactinol and raffinose may function as osmoprotectants in drought-stress tolerance of plants.
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PMID:Important roles of drought- and cold-inducible genes for galactinol synthase in stress tolerance in Arabidopsis thaliana. 1184 75

Polycyclic aromatic hydrocarbons (PAHs) in coke oven emissions cause a cancer risk to humans. In a comprehensive biomonitoring study among Estonian coke oven workers, we looked at the effect of genetic polymorphisms in metabolic enzymes on urinary mutagenicity, 1-hydroxypyrene (1-OHP) concentration in urine, and aromatic DNA adducts in white blood cells (WBCs). Coke oven workers were sampled twice (samplings I and II), and controls only once at the time of sampling I. Urinary mutagenicity was measured using the Ames test. CYP1A1, microsomal epoxide hydrolase (mEH), and glutathione S-transferase (GST) genotypes were analyzed by polymerase chain reaction (PCR). Urinary mutagenicity did not differ between exposed and controls, but those coke oven workers who were smokers had significantly higher (P=0.0002) mutagenic activity in urine than nonsmokers. Urinary mutagenicity was moderately correlated to levels of 1-OHP and aromatic DNA adducts, the P values ranging from 0.0005 to 0.002. Carriers of a variant allele in exon 4 of mEH (Arg139) had elevated urinary mutagenicity (sampling I). In addition, urine mutagenicity of persons with predicted high mEH activity was significantly higher. Smoking habit did not explain the differences observed in urinary mutagenicity between mEH phenotype or genotype subgroups. Variation in exon 3 of mEH (His113) was related to a significantly (P=0.01) higher 1-OHP concentration in exposed workers (sampling II). Workers from sampling I who had an Arg139 variation in mEH had lower levels of adducts in lymphocytes (P=0.01) than others, while airborne benzo[a]pyrene (B[a]P) and His113 variation affected interactively on adduct levels. Our study shows that a comprehensive assessment of exposure is essential for elucidation of PAH exposure at a workplace. Even at high exposures metabolic polymorphisms seem to have some effect on biomarker levels, and should be assessed in biomonitoring studies.
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PMID:The effect of relevant genotypes on PAH exposure-related biomarkers. 1185 35

The influence of the genetic deletion polymorphism of glutathione S-transferase micro 1 (GSTM1 *0/*0) on levels of anti (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE-DNA) adduct in the peripheral blood lymphocyte plus monocyte fraction (LMF) of coke-oven workers was investigated. A total of 95 male Polish coke-oven workers (60% current smokers) from two different plants comprised the sample population. Polycyclic aromatic hydrocarbons (PAH) exposure was assessed by means of the individual post-shift urinary excretion of 1-pyrenol (mean +/- S.D.: 6.93 +/- 7.20 micromol/mol creatinine; 70% of the subjects exceeded the proposed biological exposure index (BEI) 2.28 micromol/mol creatinine). Anti-BPDE-DNA adduct levels were detected by high performance liquid chromatography (HPLC)/fluorescence analysis of the anti-BPDE tetrol I-1 released after acid hydrolysis of DNA samples. Genotypes were determined by polymerase chain reaction (PCR) on the genomic DNA of each subject. Coke-oven workers without active GSTM1 (GSTM1 *0/*0, 33%) had significantly higher adduct levels than those with active GSTM1 (GSTM1*1/*1 and *1/*0) (5.90 +/- 5.59 versus 3.25 +/- 2.01 adducts/10(8) bases, Mann-Whitney U-test, z = 2.53, P = 0.011), PAH exposure in the two subgroups being similar (7.06 +/- 6.83 versus 6.67 +/- 8.00 1-pyrenol micromol/mol creatinine). The highest number of GSTM1 null subjects (12/23, 39%) belonged to the quartile with the highest adduct levels (i.e., >4.67 adducts/10(8) nucleotides). That is, coke-oven workers with GSTM1 *0/*0 genotype had a significantly higher risk of having high adduct levels than individuals with active GSTM1 genotype (Fisher exact test P = 0.0355; odds ratio (OR) = 4.145, 95% CI 1.0-18.8). Multiple linear regression analysis showed that the increase in anti-BPDE-DNA adduct levels in LMF was significantly related to the high occupational exposure to PAHs (benzo[a]pyrene (BaP)) of coke-oven workers (t = 3.087, P < 0.01) and to the lack of GSTM1 activity (t = 3.512, P < 0.001), rather than to the two other confounding factors of PAH intake, i.e. charcoal-broiled meat consumption and smoking habits. In conclusion, our results indicate the clear influence of the GSTM1 detoxifying genotype on anti-BPDE-DNA adduct formation in the LMF of coke-oven workers. This is invaluable for future environmental-occupational studies using this biomarker of PAH exposure.
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PMID:GSTM1 null genotype as a risk factor for anti-BPDE-DNA adduct formation in mononuclear white blood cells of coke-oven workers. 1503 19

Phytoremediation potentials of four poplar lines, Populus nigra (N-SL clone), Populus canescens, and two transgenic P. canescens clones were investigated using in vitro leaf discs cultures. The transgenic poplars overexpressed a bacterial gene encoding gamma-glutamylcysteine synthetase in the cytosol (11ggs) or in the chlopoplasts (6LgI), and therefore, they contained an elevated level of glutathione. Leaf discs of poplar clones were exposed to different concentrations of ZnSO(4) for 21 days. Zinc(2+) was phytotoxic only at high concentrations (10(-2) to 10(-1) M) at all P. canescens lines, but P. nigra was more sensitive. Transgenic poplars showed elevated heavy metal uptake as compared to the nontransformed clones. Treatments with zinc(2+) strongly induced the activity of glutathione S-transferase enzyme in untransformed poplar lines but to a lesser extent in the transgenic clones. These results suggest that transgenic poplars are more suitable for phytoremediation of soils contaminated with zinc(2+) than wild-type plants.
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PMID:Ability of transgenic poplars with elevated glutathione content to tolerate zinc(2+) stress. 1566 Dec 91

A biomarker study was undertaken using the Calico scallop Argopecten gibbus to assess the ecotoxicological effects of a semi-submerged municipal dump on the adjacent patch reef lagoon ecosystem (Castle harbour, Bermuda). Caged scallops were deployed in situ for 2 months at various distances from the dump (50 m, 900 m and 2.7 km) and at a reference site (14 km). A suite of biomarkers comprising metallothionein (MT), lipid peroxidation (LPO), vitellin-like proteins (Vn), glutathione S-transferase (GST), DNA strand breaks and condition factor (CF) were investigated in various tissues of the scallop (gill, digestive gland and gonad). Levels of heavy metals were also measured in the whole scallop soft tissue. While there was some variation in response between tissues, in general the results indicated that the dump was negatively impacting scallops deployed in the adjacent marine environment: elevated levels of MT, DNA strand breaks, Vn and GST and reduced condition factor were found for scallops deployed nearest to the dump and at the site 1.5 km from this point source of contamination (Tuckers town) in Castle harbour, with respect to the reference site, North Rock (although this exhibited some degree of metal contamination). The gills from scallops deployed at the dump site were the most responsive tissue, with the highest expression of MT, LPO and DNA damage. This study indicates the potential of the Calico scallop as a convenient bioindicator species in the marine tropical benthos.
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PMID:Ecotoxicological effects of a semi-submerged municipal dump (Castle harbour, Bermuda) on the Calico scallop Argopecten gibbus. 1614 Mar 43

We previously reported that a velvetleaf (Abutilon theophrasti Medic) biotype found in Maryland was resistant to atrazine because of an enhanced capacity to detoxify the herbicide via glutathione conjugation (JW Gronwald, Andersen RN, Yee C [1989] Pestic Biochem Physiol 34: 149-163). The biochemical basis for the enhanced atrazine conjugation capacity in this biotype was examined. Glutathione levels and glutathione S-transferase activity were determined in extracts from the atrazine-resistant biotype and an atrazine-susceptible or "wild-type" velvetleaf biotype. In both biotypes, the highest concentration of glutathione (approximately 500 nanomoles per gram fresh weight) was found in leaf tissue. However, no significant differences were found in glutathione levels in roots, stems, or leaves of either biotype. In both biotypes, the highest concentration of glutathione S-transferase activity measured with 1-chloro-2,4-dinitrobenzene or atrazine as substrate was in leaf tissue. Glutathione S-transferase measured with 1-chloro-2,4-dinitrobenzene as substrate was 40 and 25% greater in leaf and stem tissue, respectively, of the susceptible biotype compared to the resistant biotype. In contrast, glutathione S-transferase activity measured with atrazine as substrate was 4.4- and 3.6-fold greater in leaf and stem tissue, respectively, of the resistant biotype. Kinetic analyses of glutathione S-transferase activity in leaf extracts from the resistant and susceptible biotypes were performed with the substrates glutathione, 1-chloro-2,4-dinitrobenzene, and atrazine. There was little or no change in apparent K(m) values for glutathione, atrazine, or 1-chloro-2,4-dinitrobenzene. However, the V(max) for glutathione and atrazine were approximately 3-fold higher in the resistant biotype than in the susceptible biotype. In contrast, the V(max) for 1-chloro-2,4-dinitrobenzene was 30% lower in the resistant biotype. Leaf glutathione S-transferase isozymes that exhibit activity with atrazine and 1-chloro-2,4-dinitrobenzene were separated by fast protein liquid (anion-exchange) chromatography. The susceptible biotype had three peaks exhibiting activity with atrazine and the resistant biotype had two. The two peaks of glutathione S-transferase activity with atrazine from the resistant biotype coeluted with two of the peaks from the susceptible biotype, but peak height was three- to fourfold greater in the resistant biotype. In both biotypes, two of the peaks that exhibit glutathione S-transferase activity with atrazine also exhibited activity with 1-chloro-2,4-dinitrobenzene, with the peak height being greater in the susceptible biotype. The results indicate that atrazine resistance in the velvetleaf biotype from Maryland is due to enhanced glutathione S-transferase activity for atrazine in leaf and stem tissue which results in an enhanced capacity to detoxify the herbicide via glutathione conjugation.
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PMID:Atrazine Resistance in a Velvetleaf (Abutilon theophrasti) Biotype Due to Enhanced Glutathione S-Transferase Activity. 1666 37


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