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)

Glutathione transferases (GSTs) are often upregulated in tumors and have been suggested to play an important role in multiple drug resistance in cancer chemotherapy. As a consequence GST-dependent pro-drugs and inhibitors are being developed. Little is known, however, on the potential role of membrane-bound GSTs in drug resistance despite the fact that detoxication of cytostatic drugs and upregulation in tumors has been demonstrated. Therefore, we have studied the involvement of membrane-bound microsomal GST1 (MGST1) in cellular resistance to anticancer drugs. As a tool we have developed a cell system utilizing MCF7 cells stably overexpressing MGST1. Here, we show for the first time that MGST1 can protect cells from several cytostatic drugs, chlorambucil, melphalan and cisplatin in an acute toxicity test (MTT assay) as well as a long-term colony forming efficiency cytotoxicity test. It is of note that these cells do not overexpress multidrug transporters, a prerequisite for protection with certain other GSTs investigated in this system. The cytostatic drugs used comprise both those that are known/predicted to be substrates as well as non-substrates. Thus, the mechanism most probably entails both direct detoxication and downstream protection of the cells from oxidative stress.
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PMID:Microsomal glutathione transferase 1 in anticancer drug resistance. 1692 Jul 37

Caffeic acid (CA) and Trolox are phenolic acids that have beneficial antioxidant effect, but the underlying mechanisms involved are not fully understood. The extent to which CA and Trolox protect against sodium nitroprusside (SNP)-induced oxidative cell injury was investigated in cultured rainbow trout gill cells. The cells exposed to SNP for 24 h displayed a dose-dependent leakage of lactate dehydrogenase (LDH) and decreased cell viability as indicated by the MTT assay (mitochondrial dehydrogenase activity). Both effects were prevented by treatment with 50 microM CA or Trolox. CA or Trolox, protected against SNP-induced caspase-3 activation and DNA fragmentation, indicating a reduction of apoptosis. Thus, the results indicate that SNP induced cell death is caspase-3 related apoptosis and the treatment with CA inhibited the apoptotic pathway. In addition, we studied the effect of CA and Trolox on expression of zinc-responsive antioxidant genes such as metallothioneins (MT), glutathione-S-transferase (GST Class pi) and glucose-6-phosphate dehydrogenase (G6PD) in cultured gill cells. CA, 100 microM, increased accumulation of mRNA for MTA, MTB, GST and G6PD in cells. Thus, in addition to its ability to sequester free radicals, CA may protect against oxidative stress through expression of zinc-induced antioxidant proteins. Because of these properties we suggest that CA could be a beneficial additive to fish feeds in aquaculture.
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PMID:Dietary phenolic antioxidants, caffeic acid and Trolox, protect rainbow trout gill cells from nitric oxide-induced apoptosis. 1711 65

Tolerance to clinically important organic nitrates such as nitroglycerin (NTG) has been experimentally related to endothelial dysfunction and vascular oxidative stress. Anti-oxidant enzymes such as the glutathione-S-transferases GSTs) could potentially play a protective role in NTG tolerance. Our previous work showed that an alpha-class glutathione-S-transferase (GSTA4-4) defends against oxidative damage in the vascular wall; therefore, we asked whether overexpression of GSTA4-4 in endothelial cells and smooth muscle cells might alter the development of tolerance to NTG. Stable transfections of mouse pancreatic islet endothelial cells (MS1) with cDNA of mGSTA4-4, and human fetal aortic vascular smooth muscle cells (FLTR) with cDNA of hGSTA4-4 were established. MTT cytotoxicity, apoptosis, nitric oxide (NO) synthases, both endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) and cyclic guanosine mono-phosphate (cGMP) were measured. Endothelial cells overexpressing mGSTA4-4, and smooth muscle cells overexpressing hGSTA4-4 were more resistant to cytotoxic injury by NTG, assessed at 24 h (p < 0.05). In both endothelial and smooth muscle cells, NTG-induced apoptosis was inhibited by GST overexpression. Following dosing in a relevant tolerance-inducing NTG protocol, we found that GSTA4-4-overexpressing cells demonstrated significant downregulation of NOS enzymes; NO release, unchanged by the tolerance protocol in both wild-type and vector-transfected cells, was augmented in GST-overexpressing cells (p < 0.01); cGMP levels in control cells fell, whereas it rose in GSTA4-4-overexpressing cells (p < 0.05). Our results demonstrate that overexpression of GST isozymes can protect endothelial cells and smooth muscle cells against oxidative stress associated with NTG, and markedly alter cellular responses to repeated doses, or tolerance. By manipulating GSTs, physiological tolerance to NTG may be diminished or eliminated.
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PMID:Manipulating glutathione-S-transferases may prevent the development of tolerance to nitroglycerin. 1730 20

This study is to clone the gene of staphylococcal enterotoxins O, obtain recombinant protein (rSEO) and investigate its activity on mice lymphocyte. Staphylococcus aureus O gene is cloned into GST gene fusion vector pGEX-4T-1. The resultant plasmid pGEX-4T-SEO was used to transform E. coLi BL21, where the GST-SEO fusion protein was expressed efficiently. Then SEO was purified by Glutathione Sepharose 4B affinity column and digested with thrombin. The bioactivity of SEO was analyzed by MTT assay on mice lymphocyte and tumor cells. The nucleotide sequence was confirmed to code for the protein correctly, and soluble SEO was expressed efficiently in E. coli BL21 with pGEX-4T-SEO. The protein purified by affinity chromatography resulted to be one single band by SDS-PAGE detection. The MTT assay of the purified rSEO demonstrated that its abilities of stimulating T cells and inhibiting the proliferation of K562, K562-ADM and B16 cells were equivalent to that of SEC in vitro. The expression plasmid pGEX-4T-SEO was constructed and the recombinant superantigen was expressed successfully, which may provide a foundation for the further research of the anticancer activity of SEO.
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PMID:[Expression and bioactivity of the cloned staphylococcal enterotoxin O]. 1805 Jul 35

The purpose of this study is to investigate the reversal effect and its mechanism of arsenic trioxide (As2O3) on multidrug resistance of gastric carcinoma cells. The concentration of vincristine (VCR) increased gradually to induce the drug resistance of gastric carcinoma cell SGC7901. MTT assay was used to determine the lethal effect of anticarcinogens on tumor cells and Western blotting assay was applied to determine the expression of P-glucoprotein (P-gp) and glutathione S-transferase (GST-s) in tumor cells. As a result, the resistance of SGC7901/VCR cells to VCR, fluorouracil and epirubicin was 16.56, 2.69 and 13.05 times, respectively, more than that of SGC7901 cells. After 24 h precondition with As2O3, RI of vincristine, fluorouracil and epirubicin decreased significantly (P < 0.05). Expression of P-gp and GST-s in resting SGC7901/VCR cells was significantly higher than that in carcinogen-sensitive SGC7901 cells. As2O3 decreased the expression of P-gp and GST-s in SGC7901/VCR cells significantly, while it showed no significant effect on carcinogen-sensitive SGC7901 cells. The result suggested that As2O3 could partly reverse drug resistance of SGC7901/VCR cells by probably the mechanism of decreasing the expression of P-gp and GST-s.
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PMID:[Reversal effect and mechanism of arsenic trioxide on multidrug resistance of gastric carcinoma cells SGC7901]. 1805 Jul 36

To find a new preventive strategy for the infection of Schistosoma japonica, plasmid pIRES-Sj97-Sj14-Sj26 that contains fatty binding protein (Sj14), GST (Sj26) and paramyocin (Sj97) that are expressed on the membrane, was constructed. RT-PCR was used to detect the expression of Sj14 mRNA, Sj26 mRNA and Sj97 mRNA in the Hela cells, the indirect immunofluorescent test was employed for the detection of the expression of trans-membrane Sj26 after the plasmid was transfected into Hela cells. Fifty BALB/c mice were randomly divided into 5 groups and pIRES-Sj97-Sj14-Sj26 plasmid DNA, pIRES-Sj14-Sj26 plasmid DNA, pIRES-Sj26 plasmid DNA, pIRES blank vector and normal saline were respectively injected into the quadriceps muscles of thigh. Eight weeks after the immunization the mice were killed and significantly higher level of IgG was detected in the pIRES-Sj97-Sj14-Sj26 group as compared with the pIRES blank vector, normal saline and pIRES-Sj26 groups (P<0.01) and the pIRES-Sj14-Sj26(P<0.05). Single splenocyte suspension was prepared to detected the level of IFN-gamma by ELISA and the lymphocyte stimulating index (SI) by MTT. SI was significantly higher of in the pIRES-Sj97-Sj14-Sj26 group than in other groups (P<0.01), while the IFN-gamma level was significantly higher the pIRES-Sj97-Sj14-Sj26 group than in pIRES blank vector and normal saline groups (P<0.01), but no significant differences were found when compared with pIRES-Sj14-Sj26 and pIRES-Sj26 groups. Flow cytometery showed that the percent-ages of CD4+ and CD8+ T cells were much higher in the pIRES-Sj97-Sj14-Sj26 group (P< 0.01, P<0.05). It was concluded that pIRES-Sj97-Sj14-Sj26 vaccine may induce stronger immune response in BALB/c mice.
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PMID:Construction and expression of DNA vaccine pIRES-Sj97-Sj14-Sj26 and its immunogenicity in mice. 1823 27

The protective effect of methanol extracts of Cassia fistula (flowers, leaves and bark) was examined in vitro in human umbilical vein endothelial cells (HUVEC) against toxicity induced by glycated protein (GFBS) in vitro. The experiments consisted of eight groups of HUVEC with five flasks in each group. Group I was treated with 15% FBS, group II with GFBS (70 microM) alone, and the other six groups were treated with GFBS plus 25 and 50 microg of each of the three types of C. fistula extracts. After 72 h of incubation, cells were collected and tested for lipid peroxidation, antioxidant enzyme activities and glutathione S-transferase (GST). The protective effect of C. fistula extracts against GFBS-induced cytotoxicity was examined in HUVEC by using trypan blue exclusion and MTT assays. Results showed that HUVEC incubated with GFBS alone showed a significant (P < 0.001) elevation of lipid peroxidation accompanied by depletion of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to decreased cytosolic GST. Treatment of HUVEC with C. fistula extracts at a concentration of 25 and 50 microg significantly decreased lipid peroxidation and normalized the activities of the antioxidant enzymes and GST levels in a concentration-dependent manner. Morphological changes of HUVEC were compared with respective controls; in addition, the C. fistula extracts increased the viability of HUVEC damaged by GFBS. A protective effect of C. fistula extracts on HUVEC against GFBS-induced toxicity suggested a potential beneficial effect of the extract in preventing diabetic angiopathies.
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PMID:Protective effect of different parts of Cassia fistula on human umbilical vein endothelial cells against glycated protein-induced toxicity in vitro. 1908 44

The aim of this study was to establish a stable, drug-resistant esophageal squamous cell carcinoma (ESCC) cell line. The human ESCC cell line EC109 was exposed to cisplatin (CDDP) by pulse treatment to select for the drug-resistant subline, EC109/CDDP cells. The MTT assay was used to test the drug resistance of EC109 and EC109/CDDP cells. In addition, cellular morphological changes were observed using microscopy and the growth curves of the two cell lines were drawn to calculate the doubling time. Furthermore, cell cycle distribution was analyzed by flow cytometry. Finally, RT-PCR was performed to determine the mRNA expression levels of drug-resistant-related genes, multidrug resistance 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), ATP-binding cassette, sub-family G, member 2 (ABCG2), lung resistance protein (LRP), and glutathione S-transferase (GST)-pi in both cell lines. EC109/CDDP cells exhibited increased resistance to CDDP, carboplatin, 5-fluorouracil, taxol, navelbine, irinotecan and etoposide, and changes in morphology, doubling time, and cell cycle distribution were detected as compared with EC109 cells. Although there was no significant difference in MRP1, ABCG2, LRP, and GST-pi expression, MDR1 expression in EC109/CDDP cells was lower than that of EC109 cells. EC109/CDDP cells are a stable, multidrug-resistant ESCC cell line and could serve as an important tool for further research concerning ESCC drug resistance.
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PMID:Establishment and biological analysis of the EC109/CDDP multidrug-resistant esophageal squamous cell carcinoma cell line. 1951 6

Female adult bovine filarial worms Setaria digitata were extracted with phosphate-buffered saline (pH 7.4) and glutathione S-transferase (GST) activity and protein content were determined. The protein content, GST enzyme activity, and specific activity were 10.61 +/- 3.41 mg ml(-1), 0.09 +/- 0.019 micromol min(-1) ml(-1), and 0.009 +/- 0.002 micromol min(-1) mg(-1) protein, respectively. The GST inhibition studies were performed with and without the inhibitors resulted from earlier molecular docking studies viz., ethacrynic acid, plumbagin, and curcumin for which the IC(50) values were 19.42, 51.41, and 114.86 microM, respectively. The in vitro macrofilaricidal activity of these molecules was studied by worm motility and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay at 24- and 48-h incubation. Plumbagin and ethacrynic acid showed 100% inhibition in worm motility at lower concentrations of 3.19 and 6.6 microM, respectively, at 48-h incubation while curcumin was effective at 54.29 microM. In MTT reduction assay, the ED(50) values (50% inhibition in formazan formation) for plumbagin, ethacrynic acid, and curcumin at 48-h incubation were 1.20, 2.48, and 19.86 microM, respectively. MTT reduction assay showed that plumbagin was the most effective in killing the adult S. digitata worms followed by ethacrynic acid and curcumin. In conclusion, all the three molecules selected by molecular modeling and docking studies inhibited the GST enzyme isolated from S. digitata and exhibited macrofilaricidal activity in vitro.
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PMID:In vitro antifilarial activity of glutathione S-transferase inhibitors. 1956 76

The aim of this study was to evaluate the potential anticancer properties and modulatory effect of selected Aloe vera (A. vera) active principles on antioxidant enzyme activities. Thus, three anthraquinones (Namely: aloesin, aloe-emodin and barbaloin) were extracted from A. vera leaves by supercritical fluid extraction and subsequently purified by high performance liquid chromatography. Additionally, the N-terminal octapeptide derived from verectin, a biologically active 14 kDa glycoprotein present in A. vera, was also tested. In vivo, active principles exhibited significant prolongation of the life span of tumor-transplanted animals in the following order: barbaloin> octapeptide> aloesin > aloe-emodin. A. vera active principles exhibited significant inhibition on Ehrlich ascite carcinoma cell (EACC) number, when compared to positive control group, in the following order: barbaloin> aloe-emodin > octapeptide > aloesin. Moreover, in trypan blue cell viability assay, active principles showed a significant concentration-dependent cytotoxicity against acute myeloid leukemia (AML) and acute lymphocytes leukemia (ALL) cancerous cells. Furthermore, in MTT cell viability test, aloe-emodin was found to be active against two human colon cancer cell lines (i.e. DLD-1 and HT2), with IC(50) values of 8.94 and 10.78 microM, respectively. Treatments of human AML leukemic cells with active principles (100 microg ml(-1)) resulted in varying intensities of internucleosomal DNA fragmentation, hallmark of cells undergoing apoptosis, in the following order: aloe-emodin> aloesin> barbaloin> octapeptide. Intererstingly, treatment of EACC tumors with active principles resulted in a significant elevation activity of key antioxidant enzymes (SOD, GST, tGPx, and LDH). Our data suggest that the tested A. vera compounds may exert their chemo-preventive effect through modulating antioxidant and detoxification enzyme activity levels, as they are one of the indicators of tumorigenesis. These findings are discussed in the light of the potential of A. vera plant extracts for developing efficient, specific and non-toxic anticancer drugs that are affordable for developing countries.
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PMID:Antitumor properties and modulation of antioxidant enzymes' activity by Aloe vera leaf active principles isolated via supercritical carbon dioxide extraction. 1994 74


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