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

---

Query: KEGG:D00031 (Glutathione)
5,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione S-transferases are involved in the detoxification of carcinogens and xenobiotics and are potentially associated with the development of drug-resistance. Forty-six testicular germ cell tumors and 33 adjacent normal testicular tissue specimens were analyzed at the RNA level for the expression of glutathione S-transferase alpha and pi. Glutathione S-transferase alpha was expressed in 31 of the 33 normal testicular tissues (94%) but in only three of the 46 germ cell tumors (7%). Glutathione S-transferase pi mRNA was detected in all normal and malignant testicular tissue samples. Thirteen testicular germ cell tumors and eight normal testicular tissue samples were analyzed at the protein level. The mean specific activity of total cytosolic glutathione S-transferase in tumor tissue was decreased by about 80% as compared to normal testicular tissue. Protein analysis of the glutathione S-transferase subunits of normal testicular tissue demonstrated the presence of the glutathione S-transferase classes alpha, mu and pi, with a predominance of the mu class. In testicular germ cell tumors the glutathione S-transferase subunit pattern showed a predominance of glutathione S-transferase pi representing 88% +/- 3% of total glutathione S-transferase. Since all three glutathione S-transferase isoenzyme classes contribute to the resistance to antineoplastic drugs, the altered glutathione S-transferase isoenzyme pattern and the decrease of glutathione S-transferase activity may play a role in the high inherent drug sensitivity of human testicular germ cell tumors.
...
PMID:Glutathione S-transferases in human testicular germ cell tumors: changes of expression and activity. 131 14

Glutathione S-transferases (GSTs) play an important role in the detoxification of diverse electrophilic chemicals, including anticancer drugs. Gene-specific oligonucleotide probes were developed to monitor the expression of individual GST mRNAs in livers of adult male rats treated with drugs and other chemical modulators of GST expression. Northern blot analysis of total liver RNA using probes specific for individual GSTs belonging to classes alpha (GSTs Ya1, Ya2, Yc), mu (GSTs Yb1, Yb2, Yb3), pi (GST Yp), and GSTms demonstrated the expression in liver of all but Yp mRNA. Kidney GST expression was at least as high as that in liver for GSTs Ya1, Yc, and Yp, while it was substantially lower but still detectable for GSTs Ya2, Yb2, and GSTms. Several of the liver GST class alpha mRNAs, in particular Ya2, were inducible by pretreatment of rats with phenobarbital or isosafrole. In contrast, dexamethasone preferentially induced Yb1, Yb2, and Ya2, while two other inducers of liver drug metabolism, isoniazid and clofibrate, were less effective with respect to GST induction. GSTms mRNA was induced to a small extent or not at all by the agents tested. Treatment of adult male rats with the anticancer drug cisplatin increased liver expression of GST Yc mRNA and suppressed Ya1 mRNA levels with little or no major effect on several other GST mRNAs. Western blot analysis of liver cytosols prepared from the cisplatin-treated rats revealed corresponding changes in GST Yc and Ya protein levels. Comparable changes in liver GST Ya1 and Yc expression were effected by the cisplatin analogue iproplatin but not by carboplatin or transplatin. This pattern of response to these platinum drugs is comparable to that seen with respect to platinum drug-induced gonadal toxicity and modulation of liver cytochrome P450 expression, suggesting a common mechanistic basis for these diverse effects of platinum anticancer drugs on hepatic enzymes of drug metabolism. Together, these studies demonstrate the utility of oligonucleotide probes for phenotyping liver tissue for the expression of GST enzymes that can contribute to anticancer drug metabolism and resistance. They also raise the possibility of drug-drug interactions involving cisplatin and alkylating agent anticancer drugs that can be metabolized in liver by alpha-class GSTs.
...
PMID:Gene-specific oligonucleotide probes for alpha, mu, pi, and microsomal rat glutathione S-transferases: analysis of liver transferase expression and its modulation by hepatic enzyme inducers and platinum anticancer drugs. 139 5

Glutathione (GSH) and Glutathione S-transferase (GST) plays an important role in the protection of cells against damage from free radicals and also influences cytotoxicity to some kinds of chemotherapeutic agents. GST comprises a group of abundant and widely distributed catalytic and binding proteins that facilitate the conjugation of GSH with the electrophilic center of a large spectrum of hydrophilic molecules. Multiple GST isozymes in mammalian tissues arise from dimeric combination of a number of distinct subunits grouped into three major classes: alpha (alpha), mu (mu), and pi (p). We report the total GST, GST-p activity and GSH content of human brain tumors, C6 rat glioma cells and drug resistant C6 cells. The values of total GST activity in 42 normal brain and brain tumors were quantitatively analyzed. Total GST activity was 92.6 +/- 25.1 units (mean +/- standard deviation) in 8 samples of normal brain tissues, 126 +/- 58.8 units in five grade II or III astrocytomas (154 +/- 63.3 units in grade II astrocytomas, 84.4 +/- 2.7 units in 2 grade III astrocytoma), 66.2 +/- 29.3 in 5 glioblastoma cases, 94.7 +/- 47.7 units in 3 metastatic tumors, 302 +/- 114 unit in 8 meningiomas and 213 +/- 90.4 units in 3 neurinomas. Differences of GST activity between glioblastomas and meningiomas, grade II or III astrocytomas and meningioma, in normal brain tissues and meningioma were statistically significant (p < 0.01). The difference between normal brain tissues and benign tumors (meningiomas and neurinomas), gliomas and benign tumors were also statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Quantitative analysis of glutathione and glutathione S-transferase in human brain tumors, C6 rat glioma cells and drug resistant C6 cells]. 140 41

Mammals have separate enzymatic and cellularly mediated detoxification systems. Glutathione S-transferases (GSTs) protect against xenobiotic chemicals which continuously enter the body, largely through mucous membranes. These enzymes catalyse the conjugation of glutathione with a wide variety of electrophilic compounds rendering them non-toxic. Mammals also mount a cellular immunological response on entry of foreign cells, viruses or macromolecules into the body. T lymphocytes mobilize at the site of foreign body entry and secrete protein messengers called lymphokines. Secondary to T lymphocytes, macrophages concentrate at the infection site and function in antigen processing and phagocytosis. In vitro, macrophage movement is arrested by one class of lymphokines known as macrophage migration inhibitory factors (MIFs). We report here the purification of milligram quantities of a unique multifunctional protein from rat liver which links enzymatic and immunological detoxification systems. This protein actuates both GST and MIF activity and matches the primary structure of a human MIF in 25 out of 26 amino-terminal amino acids. Primary structure comparisons revealed significant similarity between GSTs and MIF. The glutathione affinity chromatography purification described here yields a 100-fold increase in obtaining MIF and will aid understanding of its precise biological function.
...
PMID:Rat liver protein linking chemical and immunological detoxification systems. 143 9

Glutathione S-transferases (GSTs) were isolated from rat liver, lung, heart, kidney, testis and brain by coupled affinity chromatography and subunits were resolved by reverse-phase h.p.l.c. The reverse-phase h.p.l.c. technique was improved from our previously published work [Johnson, Neal, Collins & Siegel (1990) Biochem. J. 270, 483-489] by changing from a C4 to a C18 wide-pore reverse-phase column; this resulted in baseline or near-baseline resolution of all GST subunits. There were significant tissue-dependent differences in the expression of GST subunits and the level of GST subunits present was quantitatively determined for each of the tissues. The extent of methylation of GSTs in vitro and distribution of GST methyltransferase (GST-MT) was determined in cytosolic fractions from each of these tissues. Purified GST isoenzymes were methylated with partially purified liver GST-MT. Methylation of Mu class subunits 3 and 4, the preferred substrates of methylation in liver, was substoichiometric in all tissues. The extent of methylation of subunit 3 ranged from 0.13% to 0.94% and subunit 4 from 0.03% to 0.60%. Methylation of Alpha class subunits was either not detectable or 5-10-fold less than that of Mu class subunits 3 and 4. Pi class subunit 7 was methylated to a greater extent than the Alpha class subunits but less than Mu class isoenzymes. A notable exception to this low level of methylation was GST 11-11, found mainly in testis and brain. Methylation of subunit 11 reached 21.9% (219 pmol of methyl group/nmol of subunit 11) when this isoenzyme was incubated with partially purified liver GST methyltransferase. Methylation of GST 11-11 was found to inhibit the conjugating activity of this isoenzyme towards 1-chloro-2,4-dinitrobenzene; the degree of inhibition of conjugating activity correlated with the extent of methylation of GST 11-11. GST-MT activity toward GST subunits 3, 4 and 11 was present in kidney and liver, detectable in lung and heart, but absent from brain and testis. Anion-exchange chromatography of GST-MTs from liver and kidney suggested the presence of four different forms of GST-MT (I-IV) and indicated that GST-MT isoenzymes III and IV were present at significantly lower concentrations in kidney than liver. The present paper shows that methylation is an enzyme-catalysed reaction that differs in substrate-specificity with respect to different GST isoenzymes, that expression of GST-MT is tissue-dependent and multiple forms of the enzyme are present in liver and kidney, and that methylation inhibits GST activity.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Tissue distribution of enzymic methylation of glutathione S-transferase and its effects on catalytic activity. Methylation of glutathione S-transferase 11-11 inhibits conjugating activity towards 1-chloro-2,4-dinitrobenzene. 154 Jan 44

Glutathione (GSH) plays a primary role in protecting cells from oxidative stress and in detoxifying foreign compounds. The functions and regulations of GSH in nervous tissue have not been thoroughly investigated. This study examines the effects of styrene oxide, a reactive metabolite of the neurotoxic solvent styrene, on GSH metabolism in six regions of the rat brain (cortex, cerebellum, medulla-pons, hippocampus, striatum and hypothalamus). Control levels of GSH in brain regions ranged from 1.6 mM in medulla-pons to 2.7 mM in striatum. Styrene oxide (100-400 mg/kg, ip) depleted GSH in a dose- and time-dependent manner in all brain regions studied. Histochemical studies indicated a predominantly glial distribution of GSH and confirmed the depletion of GSH by styrene oxide in brain. Studies with [8(-14)C] styrene oxide revealed no differences in the distribution of styrene oxide/metabolites among brain regions. gamma-Glutamylcysteine synthetase, the rate-limiting enzyme in GSH biosynthesis, was not affected by styrene oxide in any brain region, either in vitro or following in vivo administration. Glutathione S-transferase activity in different brain regions, measured using p-nitrostyrene oxide as a substrate, correlated quantitatively with GSH depletion by styrene oxide. Depletion of brain GSH by styrene oxide may contribute to oxidative injury to neuronal and glial cells and may be involved in styrene neurotoxicity.
...
PMID:Effect of styrene oxide on rat brain glutathione. 168 76

Glutathione S-transferases (GSTs) from Fasciola hepatica have been purified by glutathione affinity chromatography. Two closely migrating species of Mr 26,000 and 26,500 were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and several species resolved by two-dimensional gel analysis, indicating substantial heterogeneity among the GSTs. N-terminal amino acid sequencing revealed one core sequence containing three polymorphisms, whereas the sequence of GST peptides implied a minimum of three different GSTs. The amino acid sequence data assigned the F. hepatica GSTs to the mu class of GSTs with high similarities to these proteins in other helminths and mammals. The native GSTs of F. hepatica appeared to behave as dimers as determined by molecular sieving chromatography. The observation that the GSTs of F. hepatica are heterogeneous in sequence and behave as dimers in the native state suggest that these isoenzymes may exhibit considerable functional heterogeneity which may be of importance to the parasite. Immunocytochemical studies suggest that the main source of GST in F. hepatica are the parenchymal cells and peripheral tissues of the parasite. Some extracellular GST is associated with the lamellae of the intestinal epithelium. The identification of an intestinal GST is unique among trematodes studied to date.
...
PMID:Primary sequence heterogeneity and tissue expression of glutathione S-transferases of Fasciola hepatica. 173 Feb 74

Glutathione S-transferases (GSTs) of rat pancreas have been characterized and their interrelationship with fatty acid ethyl ester synthase (FAEES) has been studied. Seven GST isozymes with pI values of 9.2, 8.15, 7.8, 7.0, 6.3, 5.9 and 5.4 have been isolated and designated as rat pancreas GST suffixed by their pI values. Structural, immunological and kinetic properties of these isozymes indicated that GST 9.2 belonged to the alpha class, GST 7.8, 7.0, 6.3 and 5.9 belonged to the mu class, whereas GST 8.15 and 5.4 belong to pi class. The N-terminal sequences and pI values of the mu class isozymes suggested that rat GST subunits 3, 4 and 6 may be expressed in pancreas. N-Terminal sequences of both the pi class isozymes, GST 8.15 and 5.4, were similar to that of GST-P, but there were significant differences in the substrate specificities of these two enzymes. Results of peptide finger print studies also indicated minor structural differences between these two isozymes. None of the GST isozymes of rat pancreas expressed FAEES activity. Rat pancreas had a significant amount of FAEES activity, but it segregated independently during the purification of GST indicating that these two activities are expressed by different proteins and are not related as suggested previously.
...
PMID:Purification and characterization of glutathione S-transferases from rat pancreas. 191 52

Glutathione S-transferases (GSTs) have been reported to be elevated in some forms of hepatic carcinogenesis, in multidrug resistant (MDR) cells exhibiting elevated P-glycoprotein, and in cells resistant to alkylating agents independent of the MDR phenotype. The reported elevation of GST in association with the MDR phenotype and the overexpression of P-glycoprotein along with induction of GST in hepatic carcinogenesis suggest a correlation in the two mechanisms of cellular detoxification. To evaluate this hypothesis we examined the expression of GSTs in an MDR Chinese hamster fibroblast cell line overexpressing P-glycoprotein. We were unable to demonstrate concordant elevation of GST in these MDR cells. We conclude that GST expression is independent of P-glycoprotein expression in MDR Chinese hamster fibroblasts. The overexpression of GSTs in certain cells may provide an alternative mechanism for the development of drug resistance, either in association with or independent of P-glycoprotein overexpression, but is not essential for the MDR phenotype.
...
PMID:Glutathione S-transferase and P-glycoprotein in multidrug resistant Chinese hamster cells. 197 11

Glutathione S-transferases (GSTs), a family of isoenzymes that play an important role in protecting cells from cytotoxic and carcinogenic agents, can be separated by biochemical and immunologic characteristics into three distinct classes named alpha, mu, and pi. Previous studies have indicated that there is marked heterogeneity in the expression of different GST isoenzymes in different normal and malignant tissues. To better understand the regulation of the human pi class glutathione S-transferase isoenzyme (GST-pi), the tissue distribution of this protein wa studied by an immunohistochemical technique using an anti-GST-pi polyclonal antibody in normal paraffin-embedded human tissues. These studies indicate that there is a broad distribution of GST-pi in normal human tissues and establish a precise localization within the different organs studied. GST-pi was expressed predominantly in normal epithelial cells of the urinary, digestive, and respiratory tracts, suggesting a possible role for GST-pi in detoxication and elimination of toxic substances. Previous studies have indicated that GST-pi and the putative drug efflux pump P-glycoprotein are both overexpressed in multidrug-resistant human breast cancer cells and in xenobiotic resistant preneoplastic rat hyperplastic liver nodules. Results from this study indicate that there are also similarities between the normal tissue distribution GST-pi and that previously reported for mammalian P-glycoprotein, particularly in secretory epithelia. This finding suggests that these two gene products, which have been implicated in the development of resistance to cytotoxic drugs, may be coregulated in normal and malignant cells.
...
PMID:An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue. 197 19


1 2 3 4 5 6 7 8 9 10 Next >>

---