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: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosolic class-3 aldehyde dehydrogenase (ALDH-3) may help to protect organisms from certain environmental aldehydes by catalysing their detoxification. Consistent with this notion are the reports that relatively high levels of this enzyme are present in tissues, e.g. stomach mucosa and lung, that are so-called ports of entry for such agents. Further, it is found in human saliva. The present investigation revealed that small amounts of this enzyme are also present in human salivary glands; mean values for ALDH-3 activities (NADP-dependent enzyme-catalysed oxidation of benzaldehyde) in cytosolic fractions prepared from submandibular and parotid glands were 52 (range: 29-92) and 44 (range: 13-73) mIU/g tissue, respectively. Essentially identical or slightly lower levels of this enzyme activity were found in pleomorphic adenomas, an undifferentiated carcinoma, and an adenocystic carcinomas, of the parotid gland. On the other hand, Warthin tumours, and mucoepidermoid carcinomas of the parotid gland exhibited relatively elevated levels of ALDH-3 activity; mean values were 1200 (range: 780-1880) and 810 (range: 580-1200) mIU/g tissue, respectively. The ALDH-3 found in normal salivary glands was, as judged by physical, immunological and kinetic criteria, identical to human stomach mucosa ALDH-3 whereas the ALDH-3 present in Warthin tumours, and mucoepidermoid carcinomas, of the parotid gland appeared to be a subtle variant thereof. Qualitatively paralleling the relatively elevated ALDH-3 levels in mucoepidermoid carcinomas and Warthin tumours were relatively elevated levels of glutathione S-transferase (alpha and pi) and DT-diaphorase. As was the case with ALDH-3 levels, glutathione S-transferase (alpha and pi) and DT-diaphorase levels were not elevated in pleomorphic adenomas. Glutathione S-transferase mu was not detected in the two normal parotid gland samples, or in the single pleomorphic adenoma sample, tested. It was found in the single mucoepidermoid carcinoma sample, and in one of the two Warthin tumour samples tested. Cellular levels of ALDH-3, glutathione S-transferases and/or DT-diaphorase could be useful criteria when the decision to be made is whether a salivary gland tumour is a mucoepidermoid carcinoma. ALDH-3 and glutathione S-transferases are known to catalyse the detoxification of two agents that are used to treat salivary gland tumours, viz. cyclophosphamide and cisplatin, respectively. Thus, elevated levels of these enzymes in the mucoepidermoid carcinomas must account for, or at least contribute to, the relative ineffectiveness of these agents when used to treat this tumour.
...
PMID:Over-expression of glutathione S-transferases, DT-diaphorase and an apparently tumour-specific cytosolic class-3 aldehyde dehydrogenase by Warthin tumours and mucoepidermoid carcinomas of the human parotid gland. 893 51

A resistant subline (AH130/5A) selected from rat hepatoma AH130 cells after exposure to adriamycin (ADM) showed remarkable resistance to multiple antitumor drugs, including mitomycin C (MMC) and porfiromycin (PFM). PFM, vinblastine (VLB), and ADM accumulated in AH130/5A far less than in the parent AH130 (AH130/P) cells. AH130/5A cells showed overexpression of P-glycoprotein (PGP), an increase in glutathione S-transferase activity, and a decrease in DT-diaphorase and glutathione peroxidase activity. The resistance to MMC and VLB of AH130/5A cells was partly reversed by H-87, an inhibitor of PGP. Buthionine sulfoximine, an inhibitor of glutathione synthase, did not affect the action of MMC. tert-Butylhydroquinone induced DT-diaphorase activity, increased PFM uptake, and enhanced the growth-inhibitory action of MMC in AH130/5A cells. Dicumarol, an inhibitor of DT-diaphorase, decreased PFM uptake and reduced the growth-inhibitory action of MMC in AH130/P cells. These results indicated that the adriamycin treatment of hepatoma cells caused multifactorial multidrug resistance involving a decrease in DT-diaphorase activity.
...
PMID:Establishment by adriamycin exposure of multidrug-resistant rat ascites hepatoma AH130 cells showing low DT-diaphorase activity and high cross resistance to mitomycins. 904 1

The dioxin-inducible mouse [Ah] battery contains at least six genes that "cross-talk" with one another and are believed to play important roles in reproduction and development, and in environmental toxicity, cancer, and oxidative stress. In addition to two P450 genes, Cyp1a1 and Cyp1a2, this laboratory has shown that the four Phase II [Ah] genes include: NAD(P)H:menadione oxidoreductase (Nmo1); a cytosolic "class 3" aldehyde dehydrogenase (Ahd4); a UDP glucuronosyltransferase having 4-methylumbelliferone as substrate (Ugt1a6); and a glutathione transferase having 2,4-dinitro-1-chlorobenzene as substrate (Gsta1, Ya). The Ah receptor-mediated coordinate induction is controlled positively in all six [Ah] battery genes. Oxidative stress up-regulates the four Phase II [Ah] genes. This laboratory is generating conventional, plus inducible, knockout mouse lines having homozygous disruptions in the above-mentioned genes; this novel methodology is described herein. If the conventional knockout is healthy and viable, the mouse line would be useful for studies involving environmental agents. If the conventional knockout is lethal during development, this model would be important for developmental biology, but the inducible (also called conditional) knockout can still be used--at selected ages and even in selected tissue or cell types--for studies designed to understand the mechanisms involved in reproduction and development, and in environmental toxicity, cancer, and oxidative stress.
...
PMID:How knockout mouse lines will be used to study the role of drug-metabolizing enzymes and their receptors during reproduction and development, and in environmental toxicity, cancer, and oxidative stress. 906 27

MX100 is an Escherichia coli K12 genotoxicity tester strain, especially developed for mechanistic studies of chemical mutagens and carcinogens. For the study of the role of specific enzymes in the bioactivation and bioinactivation of carcinogens, it is necessary to characterize MX100 as far as its metabolic bio(in)activation capacities are concerned. In this study such a characterization is performed in two types of cell-free lysates, one derived from stationary phase cells, grown in rich medium (SR-lysates) and one from exponentially growing cells (log phase), cultured in minimal medium (LM-lysates). Six Phase I enzyme activities of aromatic NADPH hydroxylase, NADH hydroxylase, flavin-containing monooxygenase (FMO), nitroreductase, DT-diaphorase and NADPH ferredoxin:oxidoreductase were determined. Activities of six Phase II enzymes glutathione S-transferases (GSTs), N-aryl acetyltransferase (NAT), arylamine sulphotransferase, UDP-glucuronyltransferase and epoxide hydratase and of the Phase III enzyme cysteine conjugate beta-lyase were subsequently assessed. In addition, five antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione (GSH)-reductase, GSH-peroxidase and alkyl hydroperoxide reductase; as well as concentrations of glutathione (GSH) and its disulphide (GSSG), were measured. The activity parameters of all enzymes were compared with those obtained in similar lysates of the Salmonella strain TA100 and in rat liver preparations. The results indicate that MX100 as well as TA100 contain relatively low oxidative but high reductase Phase I activities. Both strains demonstrated low activities for the Phase II conjugation enzymes except for GSTs. In MX100, relatively high activities were detected for all antioxidative enzymes, activities which were lower in TA100. Significant differences in activities were observed between the SR-lysates derived from stationary phase/rich medium and LM-lysates from log phase/minimal medium cells for nitroreductase, GST, SOD, catalase, NADPH ferredoxin:oxidoreductase as well as in GSH content. In general, we described for the first time a metabolic characterization of the E.coli tester strain MX100 and the Salmonella typhimurium strain TA100 and discussed the results in terms of its significance for carcinogen bioactivation and bioinactivation capacities.
...
PMID:Characterization of enzyme activities and cofactors involved in bioactivation and bioinactivation of chemical carcinogens in the tester strains Escherichia coli K12 MX100 and Salmonella typhimurium LT2 TA100. 923 69

In 10 human cancer cell lines, the activity of mitomycin C (MMC) was found to be determined by an interplay between activation by DT-diaphorase (DTD) and inactivation by glutathione S-transferase (GST). NADPH/cytochrome P-450 reductase was not responsible for MMC activation and expression of MDRI (Mr 170,000 P-glycoprotein), and MRP (multidrug resistance-associated protein) genes did not relate to MMC resistance. Gene expression analysis for NQO1 (DTD gene) and GSTpi predicted which enzyme activity predominated in a cell line, except K562 and K562/DOX. For tumors with DTD activity only, MMC given by itself was most active. In cell lines in which DTD action was predominant, tumor selectivity was achieved by enhancing DTD-mediated activation with m-iodobenzylguanidine and hyperglycemia, which reduced the intra-tumoral pH. KW2149, a novel MMC analogue activated by glutathione, was most active against tumors in which GSTpi predominated. These various enzyme-specific effects could be observed even in cell lines derived from tumors with multidrug resistance. Such MMC treatment based on cell enzymology may enhance significantly MMC efficacy, helping to overcome multidrug resistance.
...
PMID:Molecular targeting of mitomycin C chemotherapy. 925 6

The ability of soy to induce phase II detoxification enzymes was evaluated in male Sprague-Dawley rats. Soybeans contain biologically active compounds that are known inducers of phase II enzyme activity. Rats were fed soy flour (SF) or soy protein isolate (SPI) to provide 75% of total protein as soy. Rats were given free access to food for one- and two-week periods before enzyme activity was compared with that of casein control groups (AIN-93G). Hepatic glutathione S-transferase (GST) activity was significantly greater in rats fed SF for one and two weeks and in rats fed SPI for two weeks than in controls. Quinone reductase activity was significantly greater (12- to 14-fold) in the colon of rats fed SF and SPI for two weeks and in serum (1.8- to 2-fold) in the SF group at one and two weeks. Liver, kidney, and small intestine uridine 5'-diphosphate-glucuronosyl transferase activity was significantly increased in the SPI and SF groups at two weeks. A time dependence in induction of phase II enzymes was observed in several tissues. There was no significant difference in total liver glutathione in either diet group compared with controls. The data indicate that dietary soy enhances phase II enzyme activity, especially quinone reductase and uridine 5'-diphosphate-glucuronosyl transferase, which could lead to protection from potentially harmful xenobiotics.
...
PMID:Soy feeding induces phase II enzymes in rat tissues. 934 36

Maintenance of cellular homeostasis is a critical survival trait in tumors when exposed to anticancer drugs. Because conjugation and elimination of drugs and their metabolites is dependent upon sequential and coordinated pathways, acquired drug resistance through a gradual adaptive response would rarely be expected to be the consequence of changes in the expression of one gene product. We have used a number of drug-resistant human cell lines to characterize those genes that are implicated in maintaining a resistant phenotype. Human HT29 colon cancer cells chronically exposed to ethacrynic acid (EA) [a glutathione (GSH) and glutathione S-transferase (GST) modulator] have acquired resistance to the drug. Commensurate with resistance, EA is more effectively conjugated to GSH and effluxed from the resistant cells. Using directed and random (differential display) approaches, a number of detoxification and/or protective gene products have been shown to be expressed at elevated levels. These include: gamma-glutamyl cysteine synthetase (gamma-GCS, the rate-limiting enzyme in GSH biosynthesis); GST pi (the enzyme catalyzing the conjugation reaction); multidrug resistance associated protein (MRP) (the membrane pump responsible for effluxing the conjugate from the cell interior). In addition, other gene products not directly linked with EA metabolism were induced, including dihydrodiol dehydrogenase (an alpha-ketoreductase) (30-fold), DT-diaphorase (threefold), and a transcriptional regulator SSP 3521 (threefold). HL60 cells resistant to a GSH paralog Ter199 also show increased expression of some of these gene products. Furthermore, an adriamycin-resistant human HL60 cell line also shows overexpression of GST pi, gamma-GCS, and MRP, but in addition has approximately 20-fold more DNA-dependent protein kinase catalytic subunit (DNA-PKcs). This enzyme is an early stress response gene that can phosphorylate and activate downstream transcription factors. Such overexpression could impact on the transcriptional control of the other detoxification gene products. Both adriamycin and a typical drug-GSH conjugate (APA-SG) are inhibitors of DNA-PK. Because cellular levels of these conjugates would presumably be a good indicator of stress, it would seem reasonable to speculate that DNA-PK may act as a receiver and transmitter of signals that are crucial to the drug-resistant phenotype. Additionally, this enzyme may prove to be a potentially important target for drug design based upon the inhibitory activity of GSH conjugates.
...
PMID:Importance of glutathione and associated enzymes in drug response. 940 35

The antischistosomal agent oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] has been shown to inhibit chemically induced carcinogenesis in a variety of animal models. Of greatest interest is its unique ability to protect several target organs from structurally diverse carcinogens. Molecular and biochemical studies suggest that oltipraz affords cellular protection by inducing the expression of a battery of Phase II detoxification enzymes. Induction of glutathione S-transferase, gamma-glutamylcysteine synthetase and DT-diaphorase has been observed in human tissues following the administration of a single oral dosage of oltipraz. Preclinical and clinical data continue to support the development of oltipraz as a chemopreventive agent for clinical usage.
...
PMID:Chemopreventive activity of oltipraz. 959 27

The critical role of the glutathione S-transferase (GST) multigene family in cellular protection in combination with the large interindividual variability in the expression of these enzymes has prompted an investigation of their importance in cancer prevention and susceptibility. Previous preclinical and clinical studies from this laboratory have established an association between decreased GST activity and increased risk for colorectal cancer. Based upon the increased incidence of colon malignancies among patients with ulcerative colitis, GST activity has been examined in a mouse model of induced colitis. Significant decreases (50% of controls) in the GST activity of colon tissue were observed during the establishment and progression of colitis. These data suggested that depletion of cellular protection may be an important event in the carcinogenic progression of ulcerative colitis. The ability of the dithiolthione oltipraz to induce GST expression within the murine colon has been demonstrated. Use of chemopreventive regimens to induce phase 2 detoxication enzyme expression represents a promising strategy for the prevention of cancer. Clinical studies revealed that the GST activity of blood lymphocytes from individuals with either a personal or family history of colorectal cancer or a personal history of colon polyps was decreased significantly when compared to that of healthy controls. Phase 1 clinical evaluation of oltipraz has demonstrated its ability to induce GST activity as well as the level of transcripts encoding gamma-glutamylcysteine synthetase (gamma-GCS) and DT-diaphorase in the colon mucosa of individuals at increased risk for colorectal cancer. The observed correlation between the posttreatment response in blood lymphocytes and colon mucosa suggested that blood lymphocytes may be used in future trials as a surrogate biomarker of the responsiveness of colon tissue to chemopreventive regimens.
...
PMID:Glutathione S-transferases--biomarkers of cancer risk and chemopreventive response. 967 68

1. A study of xenobiotic-metabolizing enzyme activity of the olfactory and respiratory epithelium in the pig was undertaken. The results indicated that porcine olfactory mucosa contains all the components of the P450 system. 2. Monooxygenase activities were much higher in olfactory than in respiratory microsomes, and the olfactory activities dependent on CYP2A were higher than those in the liver. By contrast, the olfactory monooxygenases associated with CYP2E1 were poorly or not detected, whereas CYP2G1 and a protein immunorelated to CYP1A2 were expressed in the olfactory epithelium. 3. The activities of several non oxidative enzymes (glutathione S-transferase, UDP-glucuronyl transferase, epoxide hydrolase, DT-diaphorase, benzaldehyde and propionaldehyde dehydrogenases, and various esterases) were also determined in porcine tissues and were found to be higher in the olfactory than in the respiratory mucosa, but lower or similar to those in liver. 4. An unexpected finding was a higher activity of olfactory UDP-GT compared with that of liver when 1-naphtol but not p-hydroxybiphenyl (a good substrate for a specific olfactory UDP-GT(olf) in bovine and rat) was used as substrate, suggesting a porcine specific expression of UDP-GT isoforms. 5. The results taken together indicate that the olfactory epithelium of mammals has a similar cytochrome P450 profile with the CYP2A and CYP2G1 as dominant isoforms, whereas the olfactory non-oxidative enzymes appear qualitatively and quantitatively expressed to different extents.
...
PMID:Xenobiotic-metabolizing enzymes in pig nasal and hepatic tissues. 984 40


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

---