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)

This work characterized the putative quinone oxidoreductase gene (qorA) from Staphylococcus aureus. The deduced amino acid sequence indicated that the 333 aa protein contains an NAD(P)H-binding motif. A Northern blot analysis revealed that 2.6 kb and 1.4 kb signals were detected by using a qorA probe. Both the signals were enhanced under the presence of a redox-cycling agent, 9,10-phenanthrenequinone (PQ). It was also revealed that the expression of three genes, SA1988, SA1989 (qorA) and SA1990, was enhanced at the transcriptional level by PQ exposure. The results suggested that the 2.6 kb signal detected by the qorA probe was in two co-transcripts, i.e. SA1990-qorA and qorA-SA1988 were transcribed. Besides, primer extension analyses confirmed the enhancement of qorA and SA1990 transcripts. The GST (glutathione S-transferase)-tagged QorA protein was expressed in Escherichia coli and purified using a glutathione affinity column. In purification steps, a 36 kDa band co-purified with the GST-QorA, and it was detected even in the thrombin-cleaved fraction. N-terminal amino acid sequences for the 36 kDa protein revealed that it was an intact QorA. They showed that QorA formed a multimer under physiological conditions. The purified recombinant GST-QorA catalysed NADPH consumption in the presence of PQ as a substrate, but not NADH. To characterize the catalytic activity of QorA, superoxide anion that was generated through one-electron reduction of PQ and hydroquinone that was produced by two-electron reduction of PQ were measured. During reduction of PQ by GST-QorA, superoxide anion was generated, whereas a small amount of 9,10-dihydroxyphenanthrene (hydroquinone of PQ) was produced. These results suggest that the activity of QorA is similar to zeta-Crystallin, catalysing an NADPH-dependent one-electron reduction of quinone.
...
PMID:Oxidative-stress-inducible qorA encodes an NADPH-dependent quinone oxidoreductase catalysing a one-electron reduction in Staphylococcus aureus. 1262 1

The effects of two doses (50 and 100 mg/kg body wt given orally for 14 days) of an ethanol-water (80%-20%) extract of Urtica dioica L. and butylated hydroxyanisole (BHA) were investigated, for phase I and phase II enzymes, antioxidant enzymes, lactate dehydrogenase, lipid peroxidation and sulfhydryl groups in the liver of Swiss albino mice (8-9 weeks old). A modulatory effect of two doses and BHA was also observed for the activities of glutathione S-transferase, DT-diaphorase, superoxide dismutase and catalase in the kidney, lung and forestomach, as compared with the control group. The activities of cytochrome b5 (cyt b5), NADH-cytochrome b5 reductase (cyt b5 R), glutathione S-transferase (GST), DT-diaphorase (DTD), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) showed a significant increase in the liver at both dose levels of extract. Both extract-treated showed significantly lower activity of cytochrome P450 (cyt P450), lactate dehydrogenase (LDH), NADPH-cytochrome P450 reductase (cyt P450 R), total sulfhydryl groups (T-SH), nonprotein sulfhydryl groups (NP-SH) and protein-bound sulfhydryl groups (PB-SH). BHA-treated Swiss albino mice showed a notable increase in levels of cyt b5, DTD, T-SH, PB-SH, GPx, GR, and SOD in the liver while, LDH, cyt P450, cyt P450 R, Cyt b5 R, GST, NP-SH, and CAT levels were reduced significantly as compared to control values. The extract was effective in inducing GST, DTD, SOD and CAT activity in the forestomach and SOD and CAT activity in the lung at both dose levels. BHA-treated Swiss albino mice induced DTD, GST and all antioxidative parameters in the kidney, lung and forestomach.
...
PMID:Modulatory effect of Urtica dioica L. (Urticaceae) leaf extract on biotransformation enzyme systems, antioxidant enzymes, lactate dehydrogenase and lipid peroxidation in mice. 1283 6

The chemopreventive effects of kolaviron, a natural antioxidant bioflavonoid from the seeds of Garcinia kola, on aflatoxin B1 (AFB1)-induced genotoxicity and hepatic oxidative damage was investigated in rats. Kolaviron administered orally at a dose of 200 mg/kg once a day for the first 2 weeks and then 100 mg/kg twice a day for the last 4 weeks of AFB1 (2 mg/kg, single dose, intraperitoneal) treatment reduced the AFB1-increased activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and gamma glutamyltransferase (gamma-GT) by 62%, 56% and 72% respectively. Malondialdehyde (MDA) formation and lipid hydroperoxide (LHP) accumulation were observed in the livers of AFB1-treated rats. Kolaviron significantly reduced the AFB1-induced MDA and LHP formation. Vitamins C and E were protective in reducing the increase in the activities of AST, ALT and gamma-GT as well as lipid peroxidation caused by AFB1 (P<0.01). Administration of rats with kolaviron alone resulted in significant elevation in the activities of glutathione S-transferase, uridyl glucuronosyl transferase and NADH:quinone oxidoreductase by 2.45-, 1.62- and 1.38-folds respectively. In addition, kolaviron attenuated the AFB1-mediated decrease in the activities of these enzymes (P<0.01). Pretreatment of rats with kolaviron, vitamins C and E alone did not exert genotoxicity assessed by the formation of micronucleated polychromatic erythrocytes (MNPCEs) (P>0.05). Co-treatment of rats intraperitoneally with kolaviron (500 mg/kg) 30 min before and 30 min after AFB1 (1 mg/kg) administration inhibited the induction of MNPCEs by AFB1 (P<0.001) after 72 h. While vitamin C was effective in reducing AFB1-induced MNPCEs formation, vitamin E did not elicit any antigenotoxic response. These results indicate kolaviron as effective chemopreventive agent against AFB1-induced genotoxicity and hepatic oxidative stress. Thus kolaviron may qualify for clinical trial in combating the menace of aflatoxicosis in endemic areas of aflatoxin contamination of foods.
...
PMID:Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural bioflavonoid of Garcinia kola seeds. 1590 88

To target malignant cells residing in hypoxic regions of solid tumors, we have designed and synthesized prodrugs generating the cytotoxic alkylating species 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE) after bioreductive activation. We postulate that one of these agents, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119), requires enzymatic nitro reduction to produce 90CE, whereas another agent, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(4-nitrobenzyloxy)carbonyl]hydrazine (PNBC), can also be activated by nucleophilic attack by thiols such as glutathione (GSH)/GST. We demonstrated that these agents selectively kill hypoxic EMT6 mouse mammary carcinoma and CHO cells. In hypoxia, 50 microM KS119 produced 5 logs of kill of EMT6 cells without discernable cytotoxicity in air; similar effects were observed with CHO cells. PNBC was less efficacious against hypoxic tumor cells and also had some toxicity to aerobic cells, presumably because of GST/thiol activation, making PNBC less interesting as a selective hypoxic-cell cytotoxin. BALB/c mice with established EMT6 solid tumors were used to demonstrate that KS119 could reach and kill hypoxic cells in solid tumors. To gain information on bioreductive enzymes involved in the activation of KS119, cytotoxicity was measured in CHO cell lines overexpressing NADH:cytochrome b5 reductase (NBR), NADPH:cytochrome P450 reductase (NPR), or NADPH: quinone oxidoreductase 1 (NQO1). Increased cytotoxicity occurred in cells overexpressing NBR and NPR, whereas overexpressed NQO1 had no effect. These findings were supported by enzymatic studies using purified NPR and xanthine oxidase to activate KS119. KS119 has significant potential as a hypoxia-selective tumor-cell cytotoxin and is unlikely to cause major toxicity to well oxygenated normal tissues.
...
PMID:1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine: an anticancer agent targeting hypoxic cells. 1596 88

Shewanella oneidensis contains four genes that encode proteins that have high sequence identity with yeast OYE (Old Yellow Enzyme, an NADPH oxidoreductase), the well-studied archetype of the OYE protein family. The present paper describes the first comparative study of OYEs that are present in a single bacterial species, performed to gain insight into their biochemical properties and physiological importance. The four proteins [named SYE1-SYE4 (Shewanella Yellow Enzyme 1-4)] were expressed as glutathione S-transferase fusion proteins in Escherichia coli. The yield of SYE2, however, was too low for further characterization, even after expression attempts in S. oneidensis. The SYE1, SYE3 and SYE4 proteins were found to have characteristics similar to those of other OYE family members. They were identified as flavoproteins that catalyse the reduction of different alpha,beta-unsaturated carbonyl compounds and form charge transfer complexes with a range of phenolic compounds. Whereas the properties of SYE1 and SYE3 were very similar, those of SYE4 were clearly different in terms of ligand binding, catalytic efficiency and substrate specificity. Also, the activity of SYE4 was found to be NADPH-dependent, whereas SYE1 and SYE3 had a preference for NADH. It has been suggested that yeast OYE protects the actin cytoskeleton from oxidative stress. There are indications that bacterial OYEs are also involved in the oxidative stress response, but their exact role is unclear. Induction studies in S. oneidensis revealed that yeast and bacterial OYEs may share a common physiological role, i.e. the protection of cellular components against oxidative damage. As only SYE4 was induced under oxidative stress conditions, however, a functional divergence between bacterial OYEs is likely to exist.
...
PMID:Comparative characterization and expression analysis of the four Old Yellow Enzyme homologues from Shewanella oneidensis indicate differences in physiological function. 1629 11

Cap1p, a transcription factor in Candida albicans, is thought to participate in oxidative stress tolerance, but the pathways involved are still unclear. The study was designed to reveal the possible pathways by examining changes in the transcription profile after H2O2 treatment with both the cap1-deleted strain CJD21 and its parental strain CAI4 using microarray analysis. Of the identified 89 genes differentially expressed in CAI4 after exposure to H2O2, 76 genes were in a Cap1p-dependent expression pattern. We have shown that Cap1p is involved in the oxidative stress response in C. albicans via multiple pathways, including the cellular antioxidant defense system (e.g., thioredoxin reductase, glutathione reductase, glutathione S-transferase), carbohydrate metabolism and energy metabolism (e.g., glucose-6-phosphate dehydrogenase, transaldolase, glyoxalase I, NADH-dependent flavin oxidoreductase), protein degradation (e.g., 26S proteasome regulatory subunit, ubiquitin-specific protease), ATP-dependent RNA helicase (e.g., DEAD box protein ATP-dependent RNA helicase), and resistance pathways (e.g., multidrug resistance protein, ABC transporter essential for cadmium resistance). Real-time reverse transcription-PCR analysis further confirmed the results of microarray. Collectively, this study provides new insight into the biological functions of Cap1p in oxidative stress response.
...
PMID:Cap1p is involved in multiple pathways of oxidative stress response in Candida albicans. 1654 88

Subcellular fractions (mitochondrial, cytosolic and microsomal) prepared from the tissues (hepatopancreas, muscle and gill) of freshwater prawns Macrobrachium malcolmsonii and Macrobrachium lamarrei lamarrei were scrutinized to investigate the presence of mixed function oxygenase (MFO) and conjugating enzymes (glutathione-S-transferase, GST). Cytochrome P450 (CYP) and other components (cytochrome b(5); NADPH-cytochrome c (CYP) reductase and NADH-cytochrome c-reductase activities) of the MFO system were predominantly present in the hepatic microsomal fraction of M. malcolmsonii and M. lamarrei lamarrei. The results are in agreement with the notion that monooxygenase system is mainly membrane bound in the endoplasmic reticulum, and that the hepatopancreas is the major metabolic tissue for production of biotransformation enzymes in crustaceans. Further, the prawns were exposed to two sublethal (0.9 ppt (parts per thousand) and 2.3 ppt) concentrations of oil effluent. At the end of 30th day, hydrocarbons and detoxifying enzymes were analysed in the hepatopancreas. The accumulations of hydrocarbon in the tissues gradually increased when exposed to sublethal concentrations of oil effluent and were associated with significantly enhanced levels of cytochrome P450 (180.6+/-6.34 pmol mg(-1) protein (P<0.05 versus control, 136.5+/-7.1 pmol mg(-1) protein) for 2.3 ppt and 305.6+/-8.5 pmol mg(-1) protein (P<0.001 versus control, 132.3+/-6.8 pmol mg(-1) protein] for 0.9 ppt of oil exposed M. malcolmsonii; 150+/-6.5 pmol mg(-1 )protein (P<0.01 versus control, 84.6+/-5.2 pmol mg(-1) protein) for 2.3 ppt and 175+/-5.5 pmol mg(-1) protein (P<0.01 versus control, 87.6+/-5.4 pmol mg(-1) protein) for 0.9 ppt of oil exposed M. lamarrei lamarrei), NADPH cytochrome c-reductase activity (14.7+/-0.6 nmol min(-1 )mg(-1) protein (P<0.05 versus control, 6.8+/-0.55 nmol min(-1 )mg(-1) protein) for 2.3 ppt and 12.1+/-0.45 nmol min(-1 )mg(-1) protein (P<0.01 versus control, 6.9+/-0.42 nmol min(-1 )mg(-1) protein) for 0.9 ppt of oil exposed M. malcolmsonii; 12.5+/-0.31 nmol min(-1 )mg(-1) protein (P<0.001 versus control, 4.6+/-0.45 nmol min(-1 )mg(-1) protein) for 2.3 ppt and 9.6+/-0.32 nmol min(-1 )mg(-1) protein (P<0.01 versus control, 4.9+/-0.41 nmol min(-1 )mg(-1) protein) for 0.9 ppt of oil exposed M. lamarrei lamarrei) and cytochrome b(5 )(124.8+/-3.73 pmol mg(-1) protein (P<0.01 versus control, 76.8+/-4.2 pmol mg(-1) protein) for 2.3 ppt and 115.3+/-3.86 pmol mg(-1) protein (P<0.01 versus control, 76.4+/-4.25 pmol mg(-1 )protein) for 0.9 ppt of oil exposed M. malcolmsonii and 110+/-3.11 pmol mg(-1) protein (P<0.01 versus control, 63.7+/-3.24 pmol mg(-1 )protein) for 2.3 ppt and 95.3+/-2.63 pmol mg(-1) protein (P<0.01 versus control, 61.4+/-2.82 pmol mg(-1) protein) for 0.9 ppt of oil exposed M. lamarrei lamarrei). The enhanced levels of biotransformation enzymes in oil-exposed prawns demonstrate a well-established detoxifying mechanism in crustaceans, and the response offers the possibility of use as a biomarker for the early detection of oil pollution.
...
PMID:Subcellular/tissue distribution and responses to oil exposure of the cytochrome P450-dependent monooxygenase system and glutathione S-transferase in freshwater prawns (Macrobrachium malcolmsonii, M. lamarrei lamarrei). 1667 62

A brief period of ischemia followed by timely reperfusion may lead to prolonged, yet reversible, contractile dysfunction (myocardial stunning). Damage to the myocardium occurs not only during ischemia, but also during reperfusion, where a massive release of oxygen-free radicals (OFR) occurs. We have previously utilized 2-DE and MS to define 57 protein spot changes during brief ischemia/reperfusion (15 min ischemia, 60 min reperfusion; 15I/60R) injury in a rabbit model (White, M. Y., Cordwell, S. J., McCarron, H. C. K., Prasan, A. M. et al., Proteomics 2005, 5, 1395-1410) and shown that the majority of these occur because of physical and/or chemical PTMs. In this study, we subjected rabbit myocardium to 15I/60R in the presence of the OFR scavenger N-(2-mercaptopropionyl) glycine (MPG). Thirty-seven of 57 protein spots altered during 15I/60R remained at control levels in the presence of MPG (15I/60R + MPG). Changes to contractile proteins, including myosin light chain 2 (MLC-2) and troponin C (TnC), were prevented by the addition of MPG. To further investigate the individual effects of ischemia and reperfusion, we generated 2-DE gels from rabbit myocardium subjected to brief ischemia alone (15I/0R), and observed alterations of 33 protein spots, including 18/20 seen in both 15I/60R-treated and 15I/60R + MPG-treated tissue. The tissue was also subjected to ischemia in the presence of MPG (15I/0R + MPG), and 21 spot changes, representing 14 protein variants, remained altered despite the presence of the OFR scavenger. These ischemia-specific proteins comprised those involved in energy metabolism (lactate dehydrogenase and ATP synthase alpha), redox regulation (NADH ubiquinone oxidoreductase 51 kDa and GST Mu), and stress response (Hsp27 and 70, and deamidated alpha B-crystallin). We conclude that contractile dysfunction associated with myocardial stunning is predominantly caused by OFR damage at the onset of reperfusion, but that OFR-independent damage also occurs during ischemia. These ischemia-specific protein modifications may be indicative of early myocardial injury.
...
PMID:Proteomics of ischemia and reperfusion injuries in rabbit myocardium with and without intervention by an oxygen-free radical scavenger. 1713 70

In this study, zebra mussels, D. polymorpha, were exposed to extracts of sediments obtained from two sites, a contaminated lake (Ketelmeer, Km) and a relatively clean lake (Drontenmeer, Dm). The main objective of this work was to investigate whether six selected biomarkers could discriminate between the two sediments. The selected biomarkers included phase I enzymes such as DT-diaphorase, NADPH-cytochrome c reductase, NADH-cytochrome c reductase, a phase II enzyme (glutathione S-transferase, GST), an antioxidant enzyme, catalase, and the total glutathione, reduced (GSH) and oxidized (GSSG). After a short (24 h) and a long-term (7 days) exposure, the levels of these biomarkers were measured in gills and the rest of soft mussel tissues (soft mussel tissue minus gills) and compared with control values. A decrease of GST level by 20% (P = 0.004) and a 4-fold decrease of total glutathione concentration relative to the control, were observed in the gills of mussels exposed to the more contaminated Km extract. No significant differences in the GST activities were observed in the gills of control and Dm extract-treated mussels (P = 0.23). Although the levels of catalase and NADH-cytochrome c reductase were, in the short-term exposure, unaffected, both activities were, in the long-term exposure, reduced in the gills of the mussels exposed to the contaminated Km extract, compared with control values, by 43% and 20%, respectively. The activities of DT-diaphorase and NADPH-cytochrome c reductase remained unaffected in all exposure conditions. However, the level of NADPH-cytochrome c reductase was found higher in gills than in the rest of soft mussel tissues. This difference in the ratio of the two reductases between the two tissues could account for the observed differential responses of the biomarkers.
...
PMID:Differential responses of biomarkers in tissues of a freshwater mussel, Dreissena polymorpha, to the exposure of sediment extracts with different levels of contamination. 1718 75

The present study was aimed to investigate the chemopreventive effects of Solanum trilobatum (ST) extract against diethylnitrosamine (DEN)-induced hepatocarcinogenesis promoted by Phenobarbital (PB) in Wistar rats. Hepatocarcinogenesis was initiated by a single intraperitoneal injection of DEN (200 mg/kg b.w.) and promoted with PB (0.05%) in basal diet. The experimental study extended for periods of 13 and 26 weeks. Alcoholic extract of ST was orally administered for the entire experimental period after initiation along with commencement of promotion. The chemopreventive effect of ST was assessed from the incidence of nodules, drug metabolizing phase I components such as contents of cytochrome P450, cytochrome b(5), activities of NADPH cytochrome c reductase, NADH - cytochrome b(5) reductase and phase II components such as levels of glutathione, activities of UDP-glucuronyl transferase, glutathione S-transferase and gamma-glutamyl transpeptidase in the liver. Lipid peroxidation at basal and prooxidants-induced (NADPH + ADP + Fe and Ascorbate + Fe) states was assessed in the microsomes. Animals administered with ST extract evidenced significant inhibition of tumor nodular incidence in DEN + PB + ST animals compared to DEN + PB animals, with favorable alterations in the hepatic drug-metabolizing phase I and phase II components. Administration of ST inhibited basal and pro-oxidant-induced lipid peroxidation. The present result suggests the probable mediation of chemoprevention by ST against DEN-induced carcinogenesis by the modulation of drug metabolizing components in the liver of treated animals.
...
PMID:Effect of Solanum trilobatum on hepatic drug metabolising enzymes during diethylnitrosamine-induced hepatocarcinogenesis promoted by Phenobarbital in rat. 1730 Jun 97


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

---