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

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

Fibrates are hypolipidemic pharmaceuticals that have been detected as contaminants in wastewaters and surface waters. In this work, the possible effects of two fibrates, Bezafibrate (BEZA) and Gemfibrozil (GEM) in the bivalve mollusc Mytilus spp were investigated. In the immune cells, the hemocytes, addition of both compounds in vitro induced rapid lysosomal membrane destabilization, extracellular lysozyme release, NO production and decreased phagocytic activity. The effect of fibrates were partly mediated by activation of ERK and p38 MAPKs (Mitogen Activated Protein Kinases), as demonstrated by the use of specific inhibitors of different kinases. The effects of fibrates on hemocyte function were confirmed in vivo, in the hemocytes of mussels injected with 0.01, 0.1 and 1 nmol/animal (corresponding to nominal concentrations of 3.61, 36.18 and 361.8ng/g dry weight for BEZA and of 2.50, 25.03 and 250.35 ng/g dry weight for GEM, respectively) and sampled at 24h post-injection. Both compounds induced a concentration-dependent lysosomal destabilization and extracellular lysozyme release; an increase in phagocytosis was observed at the highest concentration. In vivo exposure to fibrates also induced significant effects on mussel digestive gland, the key metabolic organ in bivalves. Both BEZA and GEM increased the activity of the glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK), and of Glutathione transferase (GST) glutathione reductase (GSR), and total glutathione content. A significant increase in the peroxisomal enzyme catalase was observed; however, BEZA exposure decreased Palmytoyl CoA oxidase activity, whereas GEM was ineffective. The results indicate that in mussels environmental concentrations of hypolipidemic drugs can affect the immune function, as well as glycolysis, redox balance and peroxisomal function.
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PMID:Effects of blood lipid lowering pharmaceuticals (bezafibrate and gemfibrozil) on immune and digestive gland functions of the bivalve mollusc, Mytilus galloprovincialis. 1757 95

The Oct-4 gene encodes a transcription factor that plays an important role in maintaining the pluripotent state of embryonic stem cells and may prevent expression of genes activated during differentiation. Although its role in maintaining embryonic stem cell pluripotency is well established, there is still little known about the binding partners that regulate its function. To identify proteins that control Oct-4 function, we used affinity chromatography on immobilized Oct-4 (POU) together with MALDI-TOF (matrix-assisted laser-desorption ionization-time-of-flight) MS (mass spectrometry) and isolated a novel Oct-4-interacting protein, pyruvate kinase type M2 (PKM2 or M2-PK). PKM2 is an isozyme of pyruvate kinase that is specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells. Oct-4 and PKM2 were co-affinity precipitated from cell extracts, and glutathione S-transferase pull-down assays revealed that the POU DNA binding domain of Oct-4 was required for interaction with PKM2. In addition, the C-terminal domain of PKM2 (amino acids 307-531) was involved in binding to Oct-4. Moreover, ectopic expression of the PKM2 enhanced Oct-4-mediated transcription. These observations indicate that the transactivation potential of the Oct-4 transcription factor is positively modulated by PKM2.
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PMID:Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription. 1819 11

Endocrine disrupting compounds (EDCs), including both natural estrogens and estrogenic chemicals, are almost ubiquitous in the aquatic environment. In the marine bivalve Mytilus galloprovincialis different estrogenic compounds, both individually and in mixtures, were shown to affect the immune function both in vitro and in vivo. Moreover, individual estrogens, the natural estrogen 17beta-estradiol (E(2)) and the xenoestrogen bisphenol A (BPA), have been recently demonstrated to alter functional parameters and gene expression in mussel digestive gland, a tissue that plays a central role in metabolism and in nutrient distribution to the gonad during gamete maturation, with possible consequences on gametogenesis. In this work, the possible effects of a synthetic mixture of EDCs on the digestive gland were evaluated. The mixture contained seven estrogenic chemicals (17beta-estradiol, 17alpha-ethynyl estradiol, mestranol (MES), nonylphenol, nonylphenol monoethoxylate carboxylate (NP1EC), BPA, benzophenone (BP)), in proportions similar to those previously found in water samples of a coastal lagoon. Mussels were injected with different concentrations of the mixture (approximate nominal concentrations of total EDCs: 0.0177, 0.177, 1.77 and 177 ng/g dw) and tissues sampled 24 h post-injection. The mixture induced significant changes in lysosomal biomarkers (lysosomal membrane stability (LMS), neutral lipid (NL) and lipofuscin (LF) accumulation) as well as in the activities of catalase, glutathione transferase (GST), and of the glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK). Moreover, downregulation of the gene transcription for the Mytilus estrogen receptor MeER1 isoform and for catalase, as evaluated by quantitative RT-PCR, were observed. Significant changes in lysosomal biomarkers, enzyme activities and gene transcription were also recorded at 72 h post-injection. The results demonstrate that short-term exposure to environmentally relevant concentrations of EDC mixtures can interfere with the lysosomal function, redox-related enzyme activities and gene transcription of mussel digestive gland.
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PMID:Short-term effects of environmentally relevant concentrations of EDC mixtures on Mytilus galloprovincialis digestive gland. 1837 27

Hepatitis C virus (HCV) replication and pathogenesis involve both virus-encoded proteins and cellular factors. In our study, we showed that NS5B, the HCV RNA-dependent RNA polymerase, interacted with M2 type pyruvate kinase (M2PK) but not L type pyruvate kinase. We confirmed the interaction by GST pull down, coimmunoprecipitation and confocal immunofluorescence analysis in cells with transient expression of NS5B and M2PK as well as in a HCV replicon-bearing cell line. Furthermore shRNA which specifically down-regulated M2PK expression could inhibit the replication of HCV in HCV replicon 9B cells.
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PMID:Isoform-specific interaction of pyruvate kinase with hepatitis C virus NS5B. 1851 40

Neuroprotein changes in the spinal cord of rodents with aliphatic gamma-diketone axonopathy induced by 2,5-hexanedione (2,5-HD) are compared with those reported previously in aromatic gamma-diketone-like axonopathy induced by 1,2-diacetylbenzene (1,2-DAB). Sprague-Dawley rats were treated intraperitoneally with 500 mg/kg/day 2,5-HD, equimolar doses of 2,3-hexanedione (negative control), or an equivalent amount of saline containing 50% dimethyl sulfoxide (vehicle), 5 days a week, for 3 weeks. Analysis of the lumbosacral proteome by 2-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight/tandem mass spectrometry revealed 34 proteins markedly modified by 2,5-HD of which neurofilament triplet L, gelsolin, protein disulfide isomerase, glutathione S-transferase, nicotinamide adenine dinucleotide (reduced) dehydrogenase 1 alpha, pyruvate kinase, and fatty acid synthase were also modified by 1,2-DAB. The expression of proteins involved in maintaining the physical integrity of the cytoskeleton or controlling the redox and protein-folding mechanisms was reduced, whereas that of proteins supporting energy metabolism was mainly increased. The similarity of the neuroproteomic patterns of 2,5-HD and 1,2-DAB axonopathy suggests common biomarkers and/or mechanisms of neurotoxicity associated with exposure to their parent chemicals, namely the industrial solvents n-hexane and 1,2-diethylbenzene, respectively.
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PMID:Probing mechanisms of axonopathy. Part II: Protein targets of 2,5-hexanedione, the neurotoxic metabolite of the aliphatic solvent n-hexane. 1903 94

Our previous studies demonstrated that retinoic acid (RA)-induced reduction of both, the key glycolytic enzyme ENO1 and proliferation-promoting c-Myc, resulted in decreased vitality and invasiveness of the follicular thyroid carcinoma cell lines FTC-133 and FTC-238. By employing two-dimensional electrophoresis and mass spectrometry, we identified proteins affected by RA treatment. In addition to previously reported decrease in ENO1 expression, we found that RA led to significantly reduced levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase isoenzymes M1/M2 (PKM1/M2), peptidyl-prolyl cis-trans isomerase A (PPIA), transketolase (TKT), annexin A2 (ANXA2), glutathione S-transferase P (GSTP1) and peroxiredoxin 2 (PRDX2) as compared to untreated control. The same proteins investigated on thyroid tissues were found to be significantly up-regulated in follicular, papillary and undifferentiated thyroid carcinomas when compared with goiter and adenoma tissues. These findings identify new target proteins for RA-mediated anti-tumor and re-differentiation therapies and provide novel insights into treatments for thyroid carcinoma.
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PMID:Proteomic approach reveals novel targets for retinoic acid-mediated therapy of thyroid carcinoma. 2053 39

Being gated by high-energy nucleotides, cardiac ATP-sensitive potassium (K(ATP)) channels are exquisitely sensitive to changes in cellular energy metabolism. An emerging view is that proteins associated with the K(ATP) channel provide an additional layer of regulation. Using putative sulfonylurea receptor (SUR) coiled-coil domains as baits in a 2-hybrid screen against a rat cardiac cDNA library, we identified glycolytic enzymes (GAPDH and aldolase A) as putative interacting proteins. Interaction between aldolase and SUR was confirmed using GST pulldown assays and coimmunoprecipitation assays. Mass spectrometry of proteins from K(ATP) channel immunoprecipitates of rat cardiac membranes identified glycolysis as the most enriched biological process. Coimmunoprecipitation assays confirmed interaction for several glycolytic enzymes throughout the glycolytic pathway. Immunocytochemistry colocalized many of these enzymes with K(ATP) channel subunits in rat cardiac myocytes. The catalytic activities of aldolase and pyruvate kinase functionally modulate K(ATP) channels in patch-clamp experiments, whereas D-glucose was without effect. Overall, our data demonstrate close physical association and functional interaction of the glycolytic process (particularly the distal ATP-generating steps) with cardiac K(ATP) channels.
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PMID:Cardiac ATP-sensitive K+ channel associates with the glycolytic enzyme complex. 2148 59

The glutathione S-transferase (GST) system is useful for increasing protein solubility and purifying soluble GST fusion proteins. However, purifying half of the GST fusion proteins is still difficult, because they are virtually insoluble under non-denaturing conditions. To optimize a simple and rapid purification condition for GST-pyruvate kinase muscle 2 (GST-PKM2) protein, we used 1% sarkosyl for lysis and a 1:200 ratio of sarkosyl to Triton X-100 (S-T) for purification. We purified the GST-PKM2 protein with a high yield, approximately 5 mg/L culture, which was 33 times higher than that prepared using a conventional method. Notably, the GST-high-temperature requirement A2 (GST-HtrA2) protein, used as a model protein for functional activity, fully maintained its proteolytic activity, even when purified under our S-T condition. This method may be useful to apply to other biologically important proteins that become highly insoluble in the prokaryotic expression system.
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PMID:Improved recovery of active GST-fusion proteins from insoluble aggregates: solubilization and purification conditions using PKM2 and HtrA2 as model proteins. 2152 55

The pathogenesis of SARS-CoV remains largely unknown. To study the function of the SARS-CoV nucleocapsid protein, we have conducted a yeast two-hybrid screening experiment to identify cellular proteins that may interact with the SARS-CoV nucleocapsid protein. Pyruvate kinase (liver) was found to interact with SARS-CoV nucleocapsid protein in this experiment. The binding domains of these two proteins were also determined using the yeast two-hybrid system. The physical interaction between the SARS-CoV nucleocapsid and cellular pyruvate kinase (liver) proteins was further confirmed by GST pull-down assay, co-immunoprecipitation assay and confocal microscopy. Cellular pyruvate kinase activity in hepatoma cells was repressed by SARS-CoV nucleocapsid protein in either transiently transfected or stably transfected cells. PK deficiency in red blood cells is known to result in human hereditary non-spherocytic hemolytic anemia. It is reasonable to assume that an inhibition of PKL activity due to interaction with SARS-CoV N protein is likely to cause the death of the hepatocytes, which results in the elevation of serum alanine aminotransferase and liver dysfunction noted in most SARS patients. Thus, our results suggest that SARS-CoV could reduce pyruvate kinase activity via its nucleocapsid protein, and this may in turn cause disease.
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PMID:SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity. 2222 84

There is a need for research studies into the molecular mechanisms underpinning the link between polycystic ovary syndrome (PCOS) and endometrial cancer (EC) to facilitate screening and to encourage the development of novel strategies to prevent disease progression. The objective of this review was to identify proteomic biomarkers of EC risk in women with PCOS. All eligible published studies on proteomic biomarkers for EC identified through the literature were evaluated. Proteomic biomarkers for EC were then integrated with an updated previously published database of all proteomic biomarkers identified so far in PCOS women. Nine protein biomarkers were similarly either under or over expressed in women with EC and PCOS in various tissues. These include transgelin, pyruvate kinase M1/M2, gelsolin-like capping protein (macrophage capping protein), glutathione S-transferase P, leucine aminopeptidase (cytosol aminopeptidase), peptidyl-prolyl cis-transisomerase, cyclophilin A, complement component C4A and manganese-superoxide dismutase. If validated, these biomarkers may provide a useful framework on which the knowledge base in this area could be developed and will facilitate future mathematical modelling to enhance screening and prevention of EC in women with PCOS who have been shown to be at increased risk.
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PMID:Proteomic biomarkers of endometrial cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration. 2352 52


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