Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Auranofin, an oral chrysotherapeutic agent effective in the treatment of rheumatoid arthritis (RA), was found to be a potent, noncytotoxic inhibitor of IgG-RF immune complex-induced lysosomal enzyme release (LER) from human leukocytes. At a concentration of 1 microg Au/ml (5 microM), auranofin produced a marked reduction in beta-glucuronidase (100%), acid phosphatase (88%), and lysozyme (72%) release. In contrast, gold sodium thiosulfate (GST, an injectable gold compound) had no inhibitory activity on LER at equivalent gold concentrations (i.e., 1 microg Au/ml) and only modest activity (less than 36% inhibition) at concentrations as high as 40 microg Au/ml. The 50% inhibitory dose (LD50) of auranofin on LER was calculated to be 3-4 microM (0.6-0.8 microg Au/ml). Blood gold levels in auranofin-treated RA patients were found to be within the range required for in vitro inhibition of LER, and correlated with decreases in IgG, RF titers, and IgG-RF immune-complex formation in vitro. These results suggest that the therapeutic action of auranofin may be caused, at least in part, by inhibition of LER and/or decreases in immune-complex formation.
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PMID:Effect of auranofin, a new antiarthritic agent, on immune complex-induced release of lysosomal enzymes from human leukocytes. 10 28

Gold sodium thiomalate added to peripheral blood mononuclear (PBM) cell cultures inhibits the mixed leukocyte reaction (MLR), and cell-mediated cytotoxicity (CMC). The addition of GST to MLR was inhibitory only if the compound was added at the beginning of culture; late addition of GST did not inhibit MLR, or CMC. In a different set of experiments the number of stimulating cells added to MLR was varied. The inhibitory effects of GST decreased markedly as the number of stimulating cells added to culture was increased. The effects of gold in vivo may be modulated by a number of immunologically competent cells that are already antigenically stimulated, as well as by the amount of available stimulating antigen.
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PMID:Inhibition of lymphocyte responses by gold: modulation by time of drug addition and antigen dose. 15 53

A vasomotor (nitritoid) reaction occurred following an initial injection of gold sodium thiomalate (GST; Myochrysine) in a 69-year-old man with rheumatoid arthritis (RA). An acute anterior wall myocardial infarction, documented by serial electrocardiographic and serum enzyme changes, developed immediately thereafter. A second patient, a 49-year-old man with RA and a history of GST-associated vasomotor reactions, was monitored clinically and electrocardiographically after GST administration. Sinus tachycardia developed and peripheral blood pressure fell within 2 minutes of injection, simultaneous with the onset of vasomotor symptoms. Vasomotor reactions from GST may compromise myocardial perfusion by their action on arteriolar smooth muscle, and thus result in peripheral vasodilatation, or they may act by adrenergic discharge initiated by such a reaction, and thus increase myocardial work and oxygen demand. Aurothioglucose (Solganal), rarely produces vasomotor reactions, and may be preferred to GST in elderly RA patients with concomitant cardiovascular disease or atherosclerosis.
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PMID:Acute myocardial infarction following gold sodium thiomalate induced vasomotor (nitritoid) reaction. 40 17

The full length cDNA of the immunodominant Ov33 protein of Onchocerca volvulus was expressed in E. coli using various vector constructs. Expression was best with the vectors pGEX2T and pCG808fx, yielding fusion protein Ov33-GST and Ov33-MBP, respectively. Purified fusion protein Ov33-GST and O. volvulus antigen extracts (OvAg) were used to compare antibody responses (IgM and IgG-subclasses) of patients infected with O. volvulus, Brugia malayi, Wuchereria bancrofti, Mansonella perstans/Loa loa and of Sudanese control sera. Sera of all groups contained IgM reacting with Ov33-GST and with OvAg. There was no IgG1 response to Ov33-GST. IgG1 responses to OvAg were only detected in filariasis sera. IgG2 and IgG3 responses were not detectable or marginal in all groups. The IgG4 reaction of onchocerciasis patients to Ov33-GST and to OvAg was high, whereas few other filariasis sera contained IgG4 antibodies to Ov33-GST and to OvAg. A serodiagnostic test for onchocerciasis based on detection of IgG4 to Ov33-GST had a sensitivity of 93.3% and a specificity of 96%. An epitope common to Ov33 and to the homologous proteins of other filarial species was demonstrated with a monoclonal antibody. Purified Ov33-MBP fusion protein was used to follow the development of the antibody response of four chimpanzees experimentally infected with O. volvulus. The data indicates that antibodies to Ov33 are induced by developing worms and later parasite stages.
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PMID:Specific and sensitive IgG4 immunodiagnosis of onchocerciasis with a recombinant 33 kD Onchocerca volvulus protein (Ov33). 128 26

Polyclonal antisera to manganese and copper-zinc superoxide dismutases, catalase, glutathione peroxidase (GPx), and isozymes of glutathione S-transferase (liver and placental isolates, GST-L and GST-P, respectively) were used to localize these enzymes in normal rat lung by immunostaining. Light-microscopic results, using an immunoperoxidase technique, were expanded on by electron-microscopic immunogold localization. The findings were consistent with previous biochemical work. However, both GPx and GST-P were predominantly localized to extracellular connective tissue of the lung. These findings demonstrate the basal antioxidant enzyme phenotypes for parenchymal lung tissue at light- and electron-microscopic levels. Significant components of enzymatic defense to oxidant stress are heterogeneously distributed throughout rat lung tissue including both epithelial cell surfaces and the extracellular matrix.
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PMID:Immunolocalization of antioxidant enzymes and isozymes of glutathione S-transferase in normal rat lung. 128 3

The use of discordant xenografts may solve some of donor shortage problems. The beneficial effects of treatment with total lymphoid irradiation (TLI) and classical drugs on this discordant model of transplantation rejection was evaluated. Twenty-four lamb hearts were transplanted heterotopically in the abdomen of 24 pigs. Group I received no treatment (control). Group II received continuous intravenous medical treatment cyclosporin A (CyA) (5 mg/kg) and azathioprine (3 mg/kg) 3 days prior to transplantation. Group III received the same medical treatment and simultaneously 12 grays of irradiation in 5 equal fractions with a high rate (100 cGy/min) or a low rate (1.6 cGy/min) prior to transplantation. Group IV also received 12 grays in 5 fractions at a high rate followed by the medical treatment started 5 days after TLI and continued until the day of transplantation. Antibody and serum cyclosporine levels were monitored. Histology specimen were analyzed at the end of the experiment. Mean GST (graft survival time) in group I and II was 140 +/- 35 min and 117 +/- 27.4 min respectively. The histological features of these hearts suggested acute humoral rejection (hemorrhage, thrombosis, and edema) without cellular infiltration. In group III, one heart functioned 4.5 days with pathological features of cellular rejection and a second animal died at 6 hours with a functioning graft with no evidence of an acute rejection. Both had been treated with the low rate TLI protocol (1.6 cGy/min). The mean GST in this group was 1080 +/- 794 min. In Group IV, one graft functioned for 6.5 days and another for 3.25 days. Mean GST was significantly increased in this group to 4800 +/- 2647 min (p < 0.05). A cellular infiltration was seen in this two grafts. The remaining graft was rejected in 6 hours with histological lesions typical of acute humoral rejection. Antibodies levels at the time of transplantation were lowest (40%) in group IV and in the low rate irradiation group. The ability of TLI to induce tolerance and to prolong survival in a discordant xenograft model depends upon cumulative dose, rate of irradiation, delay between TLI and graft placement, and combined treatment with immunosuppressive drugs. A high rate of TLI and graft placement is delayed. Low rates of irradiation may be beneficial when there is a very short period between treatment and transplantation. These findings highlight the potential usefulness of TLI in combination with immunosuppressive drug therapy when antibody-mediated rejection occurs, such as with xenograft and in sensitized patient.
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PMID:[Discordant heart xenografts. Experimental study in pigs conditioned by total lymphoid irradiation and cyclosporine A]. 129 45

The aim of our study was to investigate the suitability of Fao cells, derived from the Reuber H35 rat hepatoma as a tool for studying regulation of drug-metabolizing enzymes and drug metabolism. Fao cells express P450 2B, 2E, 3A and GST pi and were used to study the effects different inducers on these enzymes. Ethanol considerably increased the amounts of P450 2E and, to a lesser extent, P450 2B and GST pi mRNA and protein. Dexamethasone decreased the amounts of P450 2B, 3A and GST pi mRNAs, but had no appreciable effect per se upon the protein concentration of these enzymes. However, it antagonized the induction of P450 2E, 2B and GST pi by ethanol, even at the protein level. RU 486 decreased P450 2B protein and P450 2E mRNA and protein levels without effecting P450 3A and GST pi expression. RU 486 did not antagonize the dexamethasone effects, suggesting that at least some of these effects are not mediated by the glucocorticoid receptor. These data indicate that these cells constitute a suitable tool for studying the regulation of drug-metabolizing enzyme expression and drug metabolism.
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PMID:Effects of ethanol, dexamethasone and RU 486 on expression of cytochromes P450 2B, 2E, 3A and glutathione transferase pi in a rat hepatoma cell line (Fao). 130 37

Kinetic parameters of 9 substrates interaction with glutathione transferase (GST) from spring grain aphid and rat were studied. The most significant difference in Vmax values was noticed for 4-nitropyridine-N-oxide (6 times higher for aphid) and ethacrynic acid (7 times higher for rat). Km values were practically in all cases higher for aphid GST as compared to rat GST. New class of effectors of GST suggested by us, that is azimines (2 series), was used for the inhibitor analysis. GST interaction with these inhibitors was appreciated by three types of activity: nucleophilic replacement, thiolysis and N-deoxygenation. It has been shown that the degree of GST inhibition depended considerably both on the GST source and the substrate used. New high-effective inhibitors of GST were found among azimines and their higher specificity to rat GST as compared to aphid GST was demonstrated especially in thiolysis reaction.
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PMID:[A comparative study of the substrate and inhibitor specificity of the glutathione transferase from the spring grain aphid (Schizaphis gramina Rond.) and from rat liver]. 130 16

Glutathione transferase P (GST-P) is expressed at high levels in precancerous lesions and hepatocellular carcinomas from a very early stage of chemically-induced hepatocarcinogenesis in the rat. To explore the molecular mechanisms of its specific activation, we are investigating the regulation mechanisms of the GST-P gene expression. By using gene technology, we have identified a strong enhancer, GPEI, at 2.5 Kb and a silencer region at about 400 bp upstream from the transcription start site. GPEI has a palindromic structure composed of two TPA-responsive element (TRE)-like sequences and binds at least three proteins including AP-1 (c-jun/c-fos). The silencer is composed of several sequences resembling each other and binds at least three proteins including SF-B/LAP/LIP. To determine whether the GST-P gene is activated together with a putative hepato-oncogene because they are located close to each other (cis-mechanism), or because they share a trans-acting factor that can activate both genes simultaneously (trans-mechanism), transgenic rats were produced with GST-P control region connected to the CAT reporter. The results unequivocally demonstrate that GST-P gene is activated position-independently by a trans-mechanism.
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PMID:Complex regulation of a tumor marker expression. Enhancer and silencer of the GST-P gene. 130 2

The detection of preneoplastic cells is very important for the analysis of carcinogenic processes and for developing strategies for prevention and treatment of cancer. We have been investigating enzyme alterations occurring during rat chemical hepatocarcinogenesis, especially to find more specific enzyme markers for preneoplastic hepatic lesions. We identified the placental form of glutathione S-transferase (GST-P; GST 7-7) as a new marker enzyme for preneoplastic hepatocytes. We also found human placental form, GST-pi, to be a possible tumor marker for various human tissues except liver. In this article, their properties and possible functions are reviewed on basis of our recent investigations. A peroxisomal enzyme, enoyl CoA hydratase, in also described as a possible negative marker for rat preneoplastic hepatic foci/nodules and hepatomas induced by peroxisome proliferators.
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PMID:Specific expression of glutathione S-transferase Pi forms in (pre)neoplastic tissues: their properties and functions. 130 37


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