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)

1. Six enzymes which collectively catalyze a number of glutathione-dependent synthetic, catabolic and detoxification reactions were examined along with glutathione status in liver, gills, and posterior kidney of channel catfish (Ictalurus punctatus). 2. Hepatic GSH concentrations were higher than those in kidney or gills. Oxidized glutathione (GSSG) concentrations were similar among the three tissues. 3. Specific (per unit protein) gamma-glutamylcysteine synthetase (GCS) activity was greater in the gills than in liver or posterior kidney. However, total organ GCS activity was greatest in the liver. 4. Specific and total hepatic glutathione peroxidase (GSH peroxidase) activities were substantially greater than those of gills or kidney. 5. Similar specific glutathione reductase (GSSG reductase) activities were observed among all three tissues. 6. All three tissues exhibited glutathione S-transferase (GST) activity towards 1-chloro-2,4-dinitrobenzene (CDNB). Specific and total organ GST activities were highest in the liver, followed by the posterior kidney and gills. 7. Gamma-glutamyltranspeptidase (GGT) activity was present in the posterior kidney, but was undetectable in the gills or liver.
 ...
PMID:A comparison of glutathione-dependent enzymes in liver, gills and posterior kidney of channel catfish (Ictalurus punctatus). 136 Mar 60

Buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis, showed variable growth-inhibitory activity in different tumor cell lines with a high degree of inhibitory activity against melanoma-derived cell lines. A correlation between BSO growth-inhibitory effects and cellular glutathione peroxidase activity was observed. In contrast, no correlation was demonstrated between the response to BSO and cellular tyrosinase, gamma-glutamylcysteine synthetase, glutathione transferase, gamma-glutamyl transpeptidase, or glutathione reductase activities. BSO enhanced 3,4-dihydroxybenzylamine (3,4-DHBA) (fourfold) and melphalan (threefold) in vitro cytotoxic activity as determined by inhibition of DNA synthesis in human melanoma cells and this enhancement was dependent on the duration of exposure to drug. BSO demonstrated in vivo antitumor activity in B16 melanoma-bearing mice prolonging survival by 29% and in combination with 3,4-DHBA resulted in a slight (48% versus 38%) increase in life span as compared to 3,4-DHBA alone. The combination of BSO and melphalan, however, increased the life span of B16 melanoma-bearing mice by 170%, as compared to melphalan alone (80%). These studies demonstrate a unique in vivo antimelanoma activity of BSO.
 ...
PMID:Melanoma cytotoxicity of buthionine sulfoximine (BSO) alone and in combination with 3,4-dihydroxybenzylamine and melphalan. 151 64

Metabolism of nitroglycerin (GTN) in the vascular smooth muscle is required for the drug to be effective in the treatment of angina pectoris and congestive heart failure. The usefulness of GTN is limited by the development of tolerance to the drug. The metabolism of GTN was studied in its target tissue, vascular smooth muscle. Inorganic nitrite was produced by cultured smooth muscle cells when GTN was added to the culture dish. Nitrite production increased with increasing GTN concentration and with incubation time. The enzymatic nature of GTN metabolism to nitrite was assessed by enzyme inhibition studies. Indocyanine green, a non-substrate inhibitor of glutathione S-transferase, inhibited GTN metabolism by smooth muscle cells. Cellular glutathione is also involved in GTN metabolism by the smooth muscle cell. Pretreatment with phorone, a glutathione S-transferase substrate, depleted cellular glutathione and decreased nitrite production from GTN. Pretreatment with buthionine sulfoximine, inhibitor of gamma-glutamylcysteine synthetase, decreased intracellular glutathione and caused decreased GTN metabolism in smooth muscle cells. Removal of cysteine from the smooth muscle cell incubation medium in combination with buthionine sulfoximine pretreatment decreased GTN metabolism to a lower level than buthionine sulfoximine pretreatment alone. This study shows that glutathione S-transferase and glutathione are involved in GTN metabolism by cultured smooth muscle cells.
 ...
PMID:Metabolism of nitroglycerin by smooth muscle cells. Involvement of glutathione and glutathione S-transferase. 154 Feb 13

Studies were undertaken to investigate the effect of t-butylated hydroxytoluene (BHT) on reduced glutathione (GSH) levels and related enzymes in rat ocular tissues. GSH levels were significantly enhanced when 1 microM BHT was included in the medium of rat lens cultures. BHT had a dose-dependent effect on GSH levels of lenses in cultures. Inclusion of 10 microM BHT in the culture medium resulted in a twofold increase in GSH levels of the lens within 24 hr. Increased gamma-glutamylcysteine synthetase activity concomitant with the increased amount of [35S]methionine incorporation in GSH strongly suggested that BHT caused enhanced levels of GSH in lenses by increasing de novo biosynthesis. A significant increase was also observed in glutathione S-transferase (GST) levels of lenses in culture containing BHT in the medium. Present studies also demonstrated that rat lens expresses only the mu and pi class GST isoenzymes and both these classes of isoenzymes were elevated by BHT. Oral administration of BHT to rats also resulted in enhanced in vivo levels of GSH in lens, retina and cornea. In addition, a significant in vivo increase in the levels of GST, GSH-peroxidase, GSH-reductase, gamma-glutamylcysteine synthetase, and glucose 6-phosphate dehydrogenase was observed in the lens, retina, and cornea of BHT-fed rats.
 ...
PMID:t-butylated hydroxytoluene enhances intracellular levels of glutathione and related enzymes of rat lens in vitro organ culture. 154 39

Chronic exposure of humans to toxic levels of fluoride in drinking water resulted in significant increase in blood GSH content with significant increase in the activities of erythrocyte glutathione metabolising enzymes viz., gamma-glutamylcysteine synthetase (E.C. 6.3.2.2), gamma-glutamyltranspeptidase (E.C. 2.3.2.2), GST (E.C. 2.5.1.18), GSH-Px (E.C. 1.11.1.9) and GR (E.C. 1.6.4.2). The data suggested a form of adaptation on the part of the erythrocytes to counteract the oxidative stress in red blood cells of fluorotic patients.
 ...
PMID:Erythrocyte glutathione metabolism in human chronic fluoride toxicity. 167 68

The effects of geniposide pretreatment on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1 hepatotoxicity in rats has been examined. For these studies, male Sprague-Dawley rats were treated with AFB1 (2 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate aminotransferase (AST), alanine amino-transferase (ALT) and gamma-glutamyltranspeptidase (gamma-GT). After pretreatment of animals with geniposide (10 mg/kg) daily for 3 consecutive days, the enzyme elevations were significantly suppressed. This suggested that the geniposide possessed chemopreventive effects on the early acute hepatic damage induced by AFB1. Under these experimental conditions, consistent elevation of the activities of glutathione S-transferase (GST) and gamma-glutamylcysteine synthetase but not glutathione peroxidase (GSH-Px) and gamma-glutamyltranspeptidase were observed. Treatment of rats with geniposide significantly lowered hepatic GSH and GSSG levels, but the ratio of GSH to GSSG was not changed. Geniposide treatment also decreased AFB1-DNA adduct formation in AFB1-treated animals. From these results, we suggest that the protective effect of geniposide on AFB1 hepatotoxicity in rats might be due to the hepatic tissues' defense mechanisms that involve the enhanced GST activity for AFB1 detoxication and induction gamma-glutamylcysteine synthetase for GSH biosynthesis.
 ...
PMID:Suppressive effect of geniposide on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats. 168 34

The effects of GSH depletion in a human breast cancer cell line and a multi-drug resistant subline (ADRr) were determined in a number of experimental conditions. The ADRr cells contained lower GSH concentration which cannot be explained solely on the basis of differences in cell kinetics, and yet the rate-limiting synthetic enzyme gamma-glutamylcysteine synthetase was increased 2-fold. Inhibition of GSH synthesis by BSO resulted in more rapid and more pronounced GSH depletion in ADRr compared to the wild-type cells, suggesting that enhanced GSH utilization and efflux in the resistant cells account for the lowered basal concentration. In addition, the gamma-glutamyl moiety salvage enzyme gamma-glutamyltranspeptidase was reduced markedly in the ADRr cell line. Since these cells have overexpression of the efflux pump protein P-glycoprotein, we examined the effects on cellular GSH of inhibition of the pump's function by verapamil. We found that verapamil significantly depleted cellular GSH. In a rat mammary carcinoma cell line selected in Adriamycin for multi-drug resistance, a similar molecular phenotype has been described including diminished cellular GSH concentration. Verapamil treatment of these cells also resulted in significant depletion of cellular GSH. These results are consistent with the recent report that combined treatment of BSO and verapamil has an additive effect on cytotoxicity. It is likely that decreased basal GSH concentration is due to oxidation and conjugation of it in reactions catalyzed by the enhanced peroxidase and GST found in these cells.
 ...
PMID:Glutathione depletion in human and in rat multi-drug resistant breast cancer cell lines. 199 9

Experiments were undertaken to examine the ability of selenium to protect against acetaminophen-induced hepatotoxicity and to examine possible mechanisms for this protective effect. Pretreatment of male, Sprague-Dawley rats with sodium selenite (12.5 mumol Se/kg, ip) 24 hr prior to acetaminophen administration produced a significant protection against the hepatotoxic effects of acetaminophen as assessed by a decrease in the plasma appearance of alanine aminotransferase and aspartate aminotransferase activities following acetaminophen. This was accompanied by an increase in the hepatic glutathione levels in selenium-treated animals and an inhibition in the decrease in hepatic glutathione content observed in animals receiving hepatotoxic doses of acetaminophen. Selenium pretreatment decreased the in vivo covalent binding of acetaminophen metabolites to hepatic protein, but did not alter hepatic microsomal cytochrome P-450 content or NADPH cytochrome c reductase activity, suggesting that selenium does not significantly alter the metabolism of acetaminophen to reactive electrophilic metabolites by the cytochrome P-450-dependent mixed-function oxidase enzyme system. Selenium produced an increase in the activity of gamma-glutamylcysteine synthetase which may account for the increased glutathione availability in selenium-treated animals and increased the activities of glutathione S-transferase and glucose-6-phosphate dehydrogenase. Examination of the urinary metabolite profile in selenium-treated animals revealed that the urinary excretion of acetaminophen and its metabolites was significantly increased over a 72-hr period. The increase occurred in the AAP-glucuronide metabolite while parent AAP and AAP-sulfate were actually decreased in selenium-treated rats. No change in recovery was observed in the AAP-glutathione or AAP-mercapturate urinary metabolites. While the glutathione conjugating system is enhanced by selenium treatment, amelioration of acetaminophen toxicity is most likely the result of enhanced glucuronidation which effectively diverts the amount of acetaminophen to be converted by the cytochrome P-450 system to the toxic metabolite.
 ...
PMID:Protective effects of selenium on acetaminophen-induced hepatotoxicity in the rat. 290 Nov 47

Total glutathione (GSH and GSSG) level, and the activities of gamma-glutamylcysteine synthetase, gamma-glutamyltranspeptidase (gamma-GTP), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in the liver were investigated in rats, mice, guinea pigs and hamsters. Hepatic GSH level in rats, mice, guinea pigs and hamsters were 7.1, 7.8, 3.5 and 5.4 mM, respectively. The lower level of GSH in guinea pigs seems to be in part attributed to the higher activity of hepatic gamma-GTP, an enzyme which catalyzes GSH breakdown. Moreover, a marked species difference in the activities of GST, GSH-Px and GR was also observed. A 48 h-fasting resulted in a decrease of GSH and GSSG levels in rats, mice and guinea pigs, but not in hamsters. In addition, both nicotineamide adenine dinucleotide phosphate- and ascorbate-dependent lipid peroxidation produced by 9000 X g supernatant fraction in fasted animal species occurred most highly in the rat followed by hamster and guinea pig, and almost undetectable in mice. Thus, it suggests that the occurrence of lipid peroxidation in fasted animals may not be related to the hepatic GSH level, and rather, a lack of occurrence of lipid peroxidation in fasted mice may be due to the increased activity of GSH-Px activity.
 ...
PMID:Species difference in glutathione level and glutathione related enzyme activities in rats, mice, guinea pigs and hamsters. 614 91

The significance of glutathione S-conjugate in the regulation of glutathione synthesis was studied using human erythrocyte gamma-glutamylcysteine synthetase. Feedback inhibition of the enzyme by reduced glutathione was released by the addition of the glutathione S-conjugate (S-2,4-dinitrophenyl glutathione). A half-maximal effect of glutathione S-conjugate on gamma-glutamylcysteine synthetase activity was obtained at approximately 1 microM; 50 microM glutathione S-conjugate in the presence of 10 mM glutathione actually increased the enzyme activity twofold above uninhibited levels. Glutathione S-conjugate had no effect on the enzyme activity in the absence of glutathione. When erythrocytes were exposed to the electrophile 1-chloro-2,4-dinitrobenzene, which forms a glutathione S-conjugate by the catalytic reaction of glutathione S-transferase, the level of glutathione synthesis increased. These data suggest that glutathione S-conjugate plays a role in stimulating the synthesis of glutathione.
 ...
PMID:Significance of glutathione S-conjugate for glutathione metabolism in human erythrocytes. 614 24


1 2 3 4 5 6 7 8 Next >>