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)

The catalytic activities of glutathione S-transferases (GSTs), particularly the alpha-class isozymes, can provide protection against oxidative stress through GSH-mediated metabolism of reactive products of lipid peroxidation. Lipid peroxidation products from oxidative metabolism in alveolar macrophages play an important role in mediating and regulating inflammatory response and injury in the lung. The rabbit has been used as an important animal model for studies of the role of alveolar macrophages in pulmonary pathology. Although rabbit lung macrophages display GST activity, the isozyme-specific expression of GSTs and the catalytic properties of these isozymes has not previously been defined. In present studies, we have purified the GST isozymes of rabbit alveolar macrophages obtained by bronchoalveolar lavage and performed immunologic and kinetic characterization of the purified isozymes. Results of our studies indicate the presence of three alpha-class isozymes (pI 10.2, 9.3, and 6.0) and one micro-class isozyme (pI 7.2). N-terminal sequence analysis of the micro-class isozyme indicated that it was distinct from the two previously described micro-class isozymes of rabbit. Kinetic studies indicated that two cationic alpha-class GSTs (pI 10.2 and 9.3) contribute the large majority of selenium independent GSH-peroxidase activity toward dilinoleoyl phosphatidylcholine hydroperoxide (kcat/Km values of 83.4 and 31.9 s-1 . M-1 . 10(3), respectively). A third alpha-class GST (pI 6.0) was shown to have highest catalytic activity toward conjugation of the 4-hydroxynonenal (4HNE) with GSH (kcat/Km = 1900 s-1 . M-1 . 10(3)). Structural and immunologic characterization of this GST isozyme indicated that it belongs to a subclass of the alpha-classGSTs selectively expressed in mesodermal origin cells that are exposed to high levels of oxidative stress and are characterized by high specific activity toward both lipid hydroperoxides and 4-HNE.
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PMID:Glutathione S-transferases of rabbit lung macrophages. 947 30

Insect class I glutathione S-transferases (GSTs) were expressed from cDNA obtained from larvae of the Thai malaria vector. Anopheles dirus in a PCR RACE (rapid amplification of cDNA ends) reaction using a primer to the conserved N-terminal region of An. gambiae class I GSTs and a synthetic oligo d(T)-adaptor primer. Seven different plasmids, resulting from sub-cloning of an original single 0.7 Kb PCR band, were picked at random and sequenced. Four of these were clearly GSTs on the basis of putative amino acid sequence conservation. All the sequences had a conserved N-terminal region, but were highly divergent at the C-terminus. The variability in the PCR products suggests that there is a high level of GST class I isoenzyme variability in larval An. dirus. One of the subclones from the PCR reaction contained a full coding region of the cDNA for GST. This had a putative amino acid sequence which was 76 and 91% identity to the An. gambiae GST class I, agGST 1-5 and agGST 1-6 respectively, but only 48% identity to agGST 1-2. The catalytically active enzyme, expressed in Escherichia coli, was strongly immuno-cross reactive with antisera raised against the two An. gambiae class I GSTs. The expressed enzyme was purified to homogeneity from an E. coli cell lysate by S-hexylglutathione agarose affinity chromatography. The enzyme had a high specific activity with CDNB, and also used DCNB and ethacrynic acid as substrates. In addition, it had peroxidase and DDTase activity and its activity with CDNB, was strongly inhibited by a range of organophosphorus and pyrethroid insecticides. This is consistent with the predicted role of this GST class in insecticide resistance.
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PMID:Cloning, expression and characterization of an insect class I glutathione S-transferase from Anopheles dirus species B. 969 35

The gene coding for a novel glutathione S-transferase (GST) has been isolated from the bacterium Ochrobactrum anthropi. A PCR fragment of 230 bp was obtained using oligonucleotide primers deduced from N-terminal and 'internal' sequences of the purified enzyme. The gene was obtained by screening of a genomic DNA partial library from O. anthropi constructed in pBluescript with a PCR fragment probe. The gene encodes a protein (OaGST) of 201 amino acids with a calculated molecular mass of 21738 Da. The product of the gene was expressed and characterized; it showed GST activity with substrates 1-chloro-2, 4-dinitrobenzene (CDNB), p-nitrobenzyl chloride and 4-nitroquinoline 1-oxide, and glutathione-dependent peroxidase activity towards cumene hydroperoxide. The overexpressed product of the gene was also confirmed to have in vivo GST activity towards CDNB. The interaction of the recombinant GST with several antibiotics indicated that the enzyme is involved in the binding of rifamycin and tetracycline. The OaGST amino acid sequence showed the greatest identity (45%) with a GST from Pseudomonas sp. strain LB400. A serine residue in the N-terminal region is conserved in almost all known bacterial GSTs, and it appears to be the counterpart of the catalytic serine residue present in Theta-class GSTs. Substitution of the Ser-11 residue resulted in a mutant OaGST protein lacking CDNB-conjugating activity; moreover the mutant enzyme was not able to bind Sepharose-GSH affinity matrices.
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PMID:Molecular cloning, expression and site-directed mutagenesis of glutathione S-transferase from Ochrobactrum anthropi. 979 97

The current experiments were designed to study the effect of dietary n-6 and n-3 polyunsaturated fatty acids on antioxidant enzyme activity and dexamethasone (DEX)-induced apoptosis in spleen cells of sedentary (Sed) and treadmill-exercised (Ex) ICR male mice. Two-month-old mice maintained on AIN 76 formula diet, supplemented with either 5% corn oil (CO) or 5% fish oil (FO) diets, were trained on a treadmill to run from 45 to 50 min 1 km/day, 6 days a week for 12 weeks. After 12 weeks of exercise, both Sed and Ex groups were sacrificed. Blood and various tissues, including spleen, were collected asceptically. Increased serum and spleen homogenate peroxide [malondialdehyde (MDA)] levels were observed in mice fed FO (n-3 PUFA) diets, compared to mice fed CO (n-6 PUFA). However, exercise did not alter MDA levels in either CO- or FO-fed mice. Feeding n-3 PUFA significantly increased superoxide dismutase (SOD), catalase, and glutathione peroxidase activity of spleen homogenates. Exercise also significantly increased SOD and peroxidase in CO-fed animals, whereas catalase, glutathione peroxidase, and glutathione transferase were higher in FO-fed mice, compared to the Sed group. Apoptosis and necrosis were quantitated in splenocytes incubated with or without 1 microM Dex in RPMI medium for 8 and 24 hr. Cells were stained with Annexin V and propidium iodide (PI) for apoptotic and necrotic cells. FO-fed mice showed higher apoptosis (64 vs 50%) and necrosis (40 vs 22%) in spleen cells than CO-fed mice. Cells from FO-fed mice, incubated in medium alone, showed increased apoptosis (112%) 24 hr after incubation, and necrosis (37 and 70%) at 8 and 24 hr of incubation, compared to CO-fed mice. In Ex group, apoptosis was increased in both CO- and FO-fed mice only at 24 hr after incubation. In summary, these results indicate that FO (n-3 PUFA-enriched) diets increase apoptosis and antioxidant enzyme activity in spleen cells, probably due to elevated lipid peroxides.
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PMID:Modulation of antioxidant enzymes and apoptosis in mice by dietary lipids and treadmill exercise. 1008 Jan 3

A novel superfamily designated MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism), including members of widespread origin with diversified biological functions is defined according to enzymatic activities, sequence motifs, and structural properties. Two of the members are crucial for leukotriene biosynthesis, and three are cytoprotective exhibiting glutathione S-transferase and peroxidase activities. Expression of the most recently recognized member is strongly induced by p53, and may therefore play a role in apoptosis or cancer development. In spite of the different biological functions, all six proteins demonstrate common structural characteristics typical of membrane proteins. In addition, homologues are identified in plants, fungi, and bacteria, demonstrating this superfamily to be generally occurring.
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PMID:Common structural features of MAPEG -- a widespread superfamily of membrane associated proteins with highly divergent functions in eicosanoid and glutathione metabolism. 1009 72

In this genotoxic study, the Ames Salmonella microsome test showed that an aqueous extract of betel quid did not induce mutagenicity in Salmonella typhimurium strains TA98 and TA100. Mammalian cell studies (Chinese hamster ovary K1 cell; CHO-K1 cell) revealed that only higher concentrations (100 and 1000 microg/ml) of aqueous extract weekly increased the frequencies of sister-chromatid exchange (SCE) in the absence of S9. Animal (male Sprague-Dawley rat) studies showed that low-dose feeding (0.53 g dry aqueous extract/kg diet) significantly increased the activities of glutathione (GSH) peroxidase and cytoplasmic glutathione S-transferase (cGST) of liver, high-dose feeding (26.5 g dry aqueous extract/kg diet) lowered the contents of GSH and total glutathione. The effect of an aqueous extract of betel quid on the oxidation of 2'-deoxyguanosine (2'-dG) to 8-hydroxy-2'-deoxyguanosine (8-OH-dG) evaluated that this aqueous extract may act as a pro-oxidant at lower dosage and may be dependent on the iron ions in the model system. However, the aqueous extract of betel quid showed antioxidant activity at higher doses by the ability of the scavenging effect of the hydroxyl radicals.
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PMID:Chemical composition and toxicity of Taiwanese betel quid extract. 1022 37

Oxyradicals are involved in multiple mutational events and can contribute to the conversion of healthy cells to cancer cells. Glutathione (GSH) and the GSH-replenishing enzymes keep the antioxidant status of normal cells at a level where they can avert oxyradical derived mutations. The aim of this study was to determine whether in cancer cells the GSH-replenishing, GSH antioxidant and GSH-depleting enzymes were not at appropriate levels and therefore not able to protect cancer cells adequately against oxyradical-induced mutations. Cancer of the oesophagus was chosen since it is the most common gastrointestinal malignancy in South African Blacks. Biopsies and blood from 31 patients with cancer of the oesophagus and 29 non-cancer patients were assessed for these enzymes. The mean activity of the antioxidant and depleting enzyme GSH-peroxidase was elevated significantly by twofold in the cancer tissue compared to normal tissue. However, the activity of the replenishing enzyme GSSG-reductase and the level of the depleting enzyme GSH-s-transferase P1-isoenzyme were significantly reduced by 23% and 33% respectively. As in a previous paper we found that GSH was depleted and gamma-glutamine transpeptidase was diminished in oesophageal cancer. There can be two reasons for GSH depletion. Firstly, elevated GSH-peroxidase will use more GSH in an attempt to cope with the excessive production of oxyradicals as revealed by elevated lipid peroxidation; this was, as shown by us before, elevated sixfold in oesophageal cancer. Secondly, if little replenishment of GSH occurred the level of GSH would become lower. This was confirmed by our findings that the activities of the replenishing enzymes were significantly diminished in oesophageal cancer tissue. Contrary to what was expected, the other depleting enzyme GSH-s-transferase P1 was not elevated in cancer tissue but was significantly lower. However, in the blood of the same patients it was significantly elevated. An explanation for this phenomenon is that, although the production of GST-P1 was enhanced in cancer, it did not show because it was rapidly extruded into the blood by an unknown mechanism operational only in cancer cells.
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PMID:Glutathione-linked enzymes in benign and malignant oesophageal tissue. 1038 74

Aqueous extract (OE) of the leaves of Ocimum sanctum, the Indian holy basil, has been found to protect mouse against radiation lethality and chromosome damage and to possess significant antioxidant activity in vitro. Therefore a study was conducted to see if OE protects against radiation induced lipid peroxidation in liver and to determine the role, if any, of the inherent antioxidant system in radioprotection by OE. Adult Swiss mice were injected intraperitoneally (i.p.) with 10 mg/kg of OE for 5 consecutive days and exposed to 4.5 Gy of gamma radiation 30 min after the last injection. Glutathione (GSH) and the antioxidant enzymes glutathione transferase (GST), reductase (GSRx), peroxidase (GSPx) and superoxide dismutase (SOD), as well as lipid peroxide (LPx) activity were estimated in the liver at 15 min, 30 min, 1, 2, 4 and 8 hr post-treatment. LPx was also studied after treatment with a single dose of 50 mg/kg of OE with/without irradiation. OE itself increased the GSH and enzymes significantly above normal levels whereas radiation significantly reduced all the values. The maximum decline was at 30-60 min for GSH and related enzymes and at 2 hr for SOD. Pretreatment with the extract checked the radiation induced depletion of GSH and all the enzymes and maintained their levels within or above the control range. Radiation significantly increased the lipid peroxidation rate, reaching a maximum value at 2 hr after exposure (approximately 3.5 times that of control). OE pretreatment significantly (P < 0.0001) reduced the lipid peroxidation and accelerated recovery to normal levels. The results indicate that Ocimum extract protects against radiation induced lipid peroxidation and that GSH and the antioxidant enzymes appear to have an important role in the protection.
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PMID:Modulation of glutathione and antioxidant enzymes by Ocimum sanctum and its role in protection against radiation injury. 1064 Nov 57

The effects of selenium polysaccharide and sodium selenite administered by single or repetitive intraperitoneal injection (i.p.) on blood selenium concentration, the activities of liver cytochrome P450, b5 as well as NAD(P)H cytochrome C reductase, glutathione S-transferase and glutathione were studied in rats. The biological effects of selenium polysaccharide and sodium selenite were also compared. The results indicated that the blood selenium concentration was increased rapidly and reached the peak in 2 hours followed by gradual decline after selenium polysaccharide and sodium selenite were i.p. injected at a dose of Se 0.6 mg/kg. The absorption and eliminating rates of Se from sodium selenite were faster than that from selenium polysaccharide. Administration of selenium polysaccharide and sodium selenite at a dose of 0.2 mg/kg by i.p. increased the blood selenium concentration to 2.6 and 2.1 times of those of control group, respectively, and the blood selenium concentration of selenium polysaccharide group was significantly higher than that of sodium selenite group (P < 0.05). The activities of liver cytochrome P450, b5 and GST were inhibited by selenium polysaccharide and sodium selenium in vivo and in vitro experiments. Those proteins were decreased to 57%, 70% and 62% of the control, respectively, by selenium polysaccharide which has particularly stronger effects on cytochrome P-450 monooxygenase system (P < 0.05). The two selenium compounds did not appear to affect the activity of NAD(P)H cytochrome C reductase. Both of the selenium polysaccharide and sodium selenite could enhance the activity of glutathion peroxidase significantly (P < 0.05).
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PMID:[Effects of selenium polysaccharide and sodium selenite on blood selenium concentration and liver cytochrome P450 monooxygenase system in rat]. 1068 38

To examine the biological role of Al-stress-induced genes, nine genes derived from Arabidopsis, tobacco (Nicotiana tabacum L.), wheat (Triticum aestivum L.), and yeast (Saccharomyces cerevisiae) were expressed in Arabidopsis ecotype Landsberg. Lines containing eight of these genes were phenotypically normal and were tested in root elongation assays for their sensitivity to Al, Cd, Cu, Na, Zn, and to oxidative stresses. An Arabidopsis blue-copper-binding protein gene (AtBCB), a tobacco glutathione S-transferase gene (parB), a tobacco peroxidase gene (NtPox), and a tobacco GDP-dissociation inhibitor gene (NtGDI1) conferred a degree of resistance to Al. Two of these genes, AtBCB and parB, and a peroxidase gene from Arabidopsis (AtPox) also showed increased resistance to oxidative stress induced by diamide, while parB conferred resistance to Cu and Na. Al content of Al-treated root tips was reduced in the four Al-resistant plant lines compared with wild-type Ler-0, as judged by morin staining. All four Al-resistant lines also showed reduced staining of roots with 2',7'-dichloro fluorescein diacetate (H(2)DCFDA), an indicator of oxidative stress. We conclude that Al-induced genes can serve to protect against Al toxicity, and also provide genetic evidence for a link between Al stress and oxidative stress in plants.
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PMID:Expression of aluminum-induced genes in transgenic arabidopsis plants can ameliorate aluminum stress and/or oxidative stress. 1071 28


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