The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform
A Hartwig - One of the best experts on this subject based on the ideXlab platform.
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interaction of selenium compounds with zinc finger proteins involved in dna repair
FEBS Journal, 2004Co-Authors: Holger Blessing, Silke Kraus, Philipp Heindl, A HartwigAbstract:As an essential element, selenium is present in enzymes from several families, including Glutathione peroxidases, and is thought to exert anticarcinogenic properties. A remarkable feature of selenium consists of its ability to oxidize thiols under reducing conditions. Thus, one mode of action recently suggested is the oxidation of thiol groups of metallothionein, thereby providing zinc for essential reactions. However, tetrahedral zinc ion complexation to four thiolates, similar to that found in metallothionein, is present in one of the major classes of transcription factors and other so-called zinc finger proteins. Within this study we investigated the effect of selenium compounds on the activity of the formamidopyrimidine-DNA glycosylase (Fpg), a zinc finger protein involved in base excision repair, and on the DNAbinding capacity and integrity of xeroderma pigmentosum group A protein (XPA), a zinc finger protein essential for nucleotide excision repair. The reducible selenium compounds phenylseleninic acid, phenylselenyl chloride, selenocystine, ebselen, and 2-nitrophenylselenocyanate caused a concentration-dependent decrease of Fpg activity, while no inhibition was detected with fully reduced selenomethionine, methylselenocysteine or some sulfurcontaining analogs. Furthermore, reducible selenium compounds interfered with XPA–DNA binding and released zinc from the zinc finger motif, XPAzf. Zinc release was even evident at high Glutathione/oxidised glutathine ratios prevailing under cellular conditions. Finally, comparative studies with metallothionein and XPAzf revealed similar or even accelerated zinc release from XPAzf. Altogether, the results indicate that zinc finger motifs are highly reactive towards oxidizing selenium compounds. This could affect gene expression, DNA repair and, thus, genomic stability.
Antonios M Makris - One of the best experts on this subject based on the ideXlab platform.
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a novel plant Glutathione s transferase peroxidase suppresses bax lethality in yeast
Journal of Biological Chemistry, 2000Co-Authors: Sotirios C Kampranis, Radostina Damianova, Mirna Atallah, Garabet G Toby, Greta Kondi, Philip N Tsichlis, Antonios M MakrisAbstract:Abstract The mammalian inducer of apoptosis Bax is lethal when expressed in yeast and plant cells. To identify potential inhibitors of Bax in plants we transformed yeast cells expressing Bax with a tomato cDNA library and we selected for cells surviving after the induction of Bax. This genetic screen allows for the identification of plant genes, which inhibit either directly or indirectly the lethal phenotype of Bax. Using this method a number of cDNA clones were isolated, the more potent of which encodes a protein homologous to the class θ GlutathioneS-transferases. This Bax-inhibiting (BI) protein was expressed in Escherichia coli and found to possess Glutathione S-transferase (GST) and weak Glutathione peroxidase (GPX) activity. Expression of Bax in yeast decreases the intracellular levels of total Glutathione, causes a substantial reduction of total cellular phospholipids, diminishes the mitochondrial membrane potential, and alters the intracellular redox potential. Co-expression of the BI-GST/GPX protein brought the total Glutathione levels back to normal and re-established the mitochondrial membrane potential but had no effect on the phospholipid alterations. Moreover, expression of BI-GST/GPX in yeast was found to significantly enhance resistance to H2O2-induced stress. These results underline the relationship between oxidative stress and Bax-induced death in yeast cells and demonstrate that the yeast-based genetic strategy described here is a powerful tool for the isolation of novel antioxidant and antiapoptotic genes.
Ken Ng - One of the best experts on this subject based on the ideXlab platform.
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selenium enriched agaricus bisporus increases expression and activity of Glutathione peroxidase 1 and expression of Glutathione peroxidase 2 in rat colon
Food Chemistry, 2014Co-Authors: Tebo Maseko, Kate Howell, F R Dunshea, Ken NgAbstract:Abstract The effect of dietary supplementation with Se-enriched Agaricus bisporus on cytosolic gluthathione peroxidase-1 (GPx-1), gastrointestinal specific Glutathione peroxidase-2 (GPx-2), thioredoxin reductase-1 (TrxR-1) and selenoprotein P (SeP) mRNA expression and GPx-1 enzyme activity in rat colon was examined. Rats were fed for 5 weeks with control diet (0.15 μg Se/g feed) or Se-enriched diet fortified with selenised mushroom (1 μg Se/g feed). The mRNA expression levels were found to be significantly ( P P A. bisporus can positively increase GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon.
Eui Ju Choi - One of the best experts on this subject based on the ideXlab platform.
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Glutathione s transferase mu modulates the stress activated signals by suppressing apoptosis signal regulating kinase 1
Journal of Biological Chemistry, 2001Co-Authors: Hee Sae Park, Kanghyun Ryoo, Keonwook Kang, Ji Hyun Park, Tongshin Chang, Soo Yeon Choi, Jaekyung Shim, Mi Sook Dong, Hidenori Ichijo, Eui Ju ChoiAbstract:Abstract Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that can activate the c-Jun N-terminal kinase and the p38 signaling pathways. It plays a critical role in cytokine- and stress-induced apoptosis. To further characterize the mechanism of the regulation of the ASK1 signal, we searched for ASK1-interacting proteins employing the yeast two-hybrid method. The yeast two-hybrid assay indicated that mouse GlutathioneS-transferase Mu 1-1 (mGSTM1-1), an enzyme involved in the metabolism of drugs and xenobiotics, interacted with ASK1. We subsequently confirmed that mGSTM1-1 physically associated with ASK1 both in vivo and in vitro. The in vitro binding assay indicated that the C-terminal portion of mGSTM1-1 and the N-terminal region of ASK1 were crucial for binding one another. Furthermore, mGSTM1-1 suppressed stress-stimulated ASK1 activity in cultured cells. mGSTM1-1 also blocked ASK1 oligomerization. The ASK1 inhibition by mGSTM1-1 occurred independently of the Glutathione-conjugating activity of mGSTM1-1. Moreover, mGSTM1-1 repressed ASK1-dependent apoptotic cell death. Taken together, our findings suggest that mGSTM1-1 functions as an endogenous inhibitor of ASK1. This highlights a novel function for mGSTM1-1 insofar as mGSTM1-1 may modulate stress-mediated signals by repressing ASK1, and this activity occurs independently of its well-known catalytic activity in intracellular Glutathione metabolism.
Karl-dieter Entian - One of the best experts on this subject based on the ideXlab platform.
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Mutants of Saccharomyces cerevisiae sensitive to oxidative and osmotic stress
Current Genetics, 1995Co-Authors: B. Krems, C. Charizanis, Karl-dieter EntianAbstract:Although oxidative stress is involved in many human diseases, little is known of its molecular basis in eukaryotes. In a genetic approach, S. cerevisiae was used to identify elements involved in oxidative stress. By using hydrogen peroxide as an agent for oxidative stress, 34 mutants were identified. All mutants were recessive and fell into 16 complementation groups ( pos1 to pos16 for peroxide sensitivity). They corresponded to single mutations as shown by a 2:2 segregation pattern. Enzymes reportedly involved in oxidative stress, such as glucose-6-phosphate dehydrogenase, Glutathione reductase, superoxide dismutase, as well as Glutathione concentrations, were investigated in wild-type and mutant-cells. One complementation group lacked glucose-6-phosphate dehydrogenase and was shown to be allelic to the glucose-6-phosphate dehydrogenase structural gene ZWF1/MET19 . In other mutants all enzymes supposedly involved in oxidative-stress resistance were still present. However, several mutants showed strongly elevated levels of Glutathione reductase, gluconate-6-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase. One complementation group, pos9 , was highly sensitive to oxidative stress and revealed the same growth phenotype as the previously described yap1/par1 mutant coding for the yeast homologue of mammalian transcriptional activator protein, c-Jun, of the proto-oncogenic AP-1 complex. However, unlike par1 mutants, which showed diminished activities of oxidative-stress enzymes and glutathion level, the pos9 mutants did not reveal any such changes. In contrast to other recombinants between pos mutations and par1 , the sensitivity did not further increase in par1 pos9 recombinants, which may indicate that both mutations belong to the same regulating circuit. Interestingly, ten complementation groups were, in parallel, sensitive to osmotic stress, and one mutant allele revealed increased heat sensitivity. Our results indicate that a surprisingly large number of genes seem to be involved in oxidative-stress resistance and a possible overlap exists between osmotic stress and other stress reactions.
