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)

The membrane-bound NADH dehydrogenase of an alkaliphilic Bacillus YN-1 involved in the respiratory chain exhibits reductase activity for hydrogen peroxide and cumene hydroperoxide in the presence of the 22-kDa component (AhpC) from Amphibacillus xylanus (Koyama et al. Biochem. Biophys. Res. Commun. 247, 659-662). In this study, AhpC-like polypeptide with an apparent molecular mass of 20 kDa was isolated from the cell-free extract of YN-1. The NADH dehydrogenase exhibited reductase activity for cumene hydroperoxide in the presence of the purified AhpC-like component from YN-1. It is likely that the NADH dehydrogenase is not only involved in the respiratory chain, but also functions for scavenging peroxide in the presence of its own endogenous AhpC component. The enzyme expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST) showed the NADH dehydrogenase activity as high as the native enzyme from YN-1. While the fusion protein was unable to reduce cumene hydroperoxide in the presence of AhpC-like protein from YN-1, the protein obtained by the cleavage treatment of the fusion protein to release GST exhibited the reductase activity as much as the native enzyme.
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PMID:Peroxide reductase activity of NADH dehydrogenase in the presence of an endogenous 20-kDa component of an alkaliphilic Bacillus. 1108 Mar 86

Previously, we reported that the yeast cytoplasmic thiol peroxidase type II isoform (cTPx II), a member of the TSA/AhpC family, showed a very low peroxidase activity when compared with other cytoplasmic yeast isoforms, and that cTPx II mutant (cTPx II Delta) showed a severe growth retardation compared with that of the wild-type cells. To reveal the physiological function of cTPx II in yeast cell growth, we searched for proteins which react with cTPx II. In this study, we identified a novel interaction between cTPx II and CSR1p using the yeast two-hybrid system. CSR1p (SFH2p) has been known to be one member of Sec14 homologous (SFH2) proteins. SFH2p exhibits phosphatidylinositol transfer protein activity. Interestingly, we found that cTPx II selectively bound to SFH2p among the five types of SFH proteins and Sec14p. The interaction required the dimerization of cTPx II. In addition, SFH2p also specifically bound to cTPx II among the yeast thiol peroxidase isoforms. The selective interaction of the dimer form of cTPx II (the oxidized form) with SFH2p was also confirmed by glutathione S-transferase pull-down and immunoprecipitation assays. The growth retardation, clearly reflected by the length of the lag phase, of cTPx II Delta was rescued by deleting SFH2p in the cTPx II Delta strain. The SFH2 Delta strain did not show any growth retardation. In addition, the double mutant showed a higher susceptibility to oxidative stress. This finding provides the first in vivo demonstration of the specific interaction of cTPx II with SFH2p in an oxidative stress-sensitive manner and a novel physiological function of the complex of cTPx II and SFH2p.
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PMID:The protein interaction of Saccharomyces cerevisiae cytoplasmic thiol peroxidase II with SFH2p and its in vivo function. 1282 82

Glutathione S-transferase pi (GST pi) has been shown to reactivate oxidized 1-cysteine peroxiredoxin (1-Cys Prx, Prx VI, Prdx6, and AOP2). We now demonstrate that a heterodimer complex is formed between 1-Cys Prx with a C-terminal His6 tag and GST pi upon incubation of the two proteins at pH 8.0 in buffer containing 20% 1,6-hexanediol to dissociate the homodimers, followed by dialysis against buffer containing 2.5 mM glutathione (GSH) but lacking 1,6-hexanediol. The heterodimer can be purified by chromatography on nickel-nitriloacetic acid agarose in the presence of GSH. N-Terminal sequencing showed that equimolar amounts of the two proteins are present in the isolated complex. In the heterodimer, 1-Cys Prx is fully active toward either H2O2 or phospholipid hydroperoxide, while the GST pi activity is approximately 25% of that of the GST pi homodimer. In contrast, the 1-Cys Prx homodimer lacks peroxidase activity even in the presence of free GSH. The heterodimer is also formed in the presence of S-methylglutathione, but no 1-Cys Prx activity is found under these conditions. The yield of heterodimer is decreased in the absence of 1,6-hexanediol or GSH. Rapid glutathionylation of 1-Cys Prx in the heterodimer is detected by immunoblotting. Subsequently, a disulfide-linked dimer is observed on SDS-PAGE, and the free cysteine content is decreased by 2 per heterodimer. The involvement of particular binding sites in heterodimer formation was tested by site-directed mutagenesis of the two proteins. For 1-Cys Prx, neither Cys47 nor Ser32 is required for heterodimer formation but Cys47 is essential for 1-Cys Prx activation. For GST pi, Cys47 and Tyr7 (at or near the GSH-binding site) are needed for heterodimer formation but three other cysteines are not. We conclude that reactivation of oxidized 1-Cys Prx by GST pi occurs by heterodimerization of 1-Cys Prx and GST pi harboring bound GSH, followed by glutathionylation of 1-Cys Prx and then formation of an intersubunit disulfide. Finally, the GSH-mediated reduction of the disulfide regenerates the reduced active-site sulfhydryl of 1-Cys Prx.
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PMID:Direct evidence for the formation of a complex between 1-cysteine peroxiredoxin and glutathione S-transferase pi with activity changes in both enzymes. 1640 Oct 67

Sclerosing hemangioma (SH) is a rare benign pulmonary tumor derived from the primitive respiratory epithelium. However, the pathogenesis of SH has not yet been clear. Surfactant protein, thyroid transcription factor-1, epithelial membrane antigen, cytokeratin, and vimentin have been identified in SH by immunohistochemistry and electron microscopy. To identify proteins specifically regulated in SH, 2-D PAGE was performed using SH and paired normal tissues. Ten selected differentially expressed protein spots were identified by PMF, MALDI-TOF-MS, and database searching. Apolipoprotein A-1, antizyme inhibitor, heat shock 27-kDa protein 1, and antioxidant proteins, such as peroxiredoxin II (Prx II) and GST, were identified among the down-regulated proteins in SH. Western blot and immunohistochemistry confirmed reduced expressions of Prx II and GST in SH versus normal lung tissue. This study is the first report on the reduced expressions of Prx II and GST in SH.
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PMID:Proteomic analysis of pulmonary sclerosing hemangioma. 1689 84

1-Cys peroxiredoxins (1-Cys Prxs) are antioxidant enzymes that catalyze the reduction of hydroperoxides into alcohols using a strictly conserved cysteine. 1-Cys B-Prxs, homologous to human PrxVI, were recently shown to be reactivated by glutathione S-transferase (GST) pi via the formation of a GST-Prx heterodimer and Prx glutathionylation. In contrast, 1-Cys D-Prxs, homologous to human PrxV, are reactivated by the glutaredoxin-glutathione system through an unknown mechanism. To investigate the mechanistic events that mediate the 1-Cys D-Prx regeneration, interaction of the Prx with glutathione was studied by mass spectrometry and NMR. This work reveals that the Prx can be glutathionylated on its active site cysteine. Evidences are reported that the glutathionylation of 1-Cys D-Prx induces the dissociation of the Prx non-covalent homodimer, which can be recovered by reduction with dithiothreitol. This work demonstrates for the first time the existence of a redox-dependent dimer-monomer switch in the Prx family, similar to the decamer-dimer switch for the 2-Cys Prxs.
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PMID:Glutathionylation induces the dissociation of 1-Cys D-peroxiredoxin non-covalent homodimer. 1691 1

Cellular redox metabolism is considered to be involved in the pathophysiology of diseases caused by protozoal parasites such as Toxoplasma, Trypanosoma, Leishmania, and Plasmodia. Redox reactions furthermore are thought to play a major role in the action of and the resistance to some clinically used antiparasitic drugs. Interestingly, in malarial parasites, the antioxidant enzymes catalase and glutathione peroxidase are absent which indicates a crucial role of the thioredoxin system in redox control. Besides a glutathione peroxidase-like thioredoxin peroxidase and a glutathione S-transferase with slight peroxidase activity, Plasmodium falciparum (the causative agent of tropical malaria) possesses four classical peroxiredoxins: Two peroxiredoxins of the typical 2-Cys Prx class, one 1-Cys peroxiredoxin with homology to the atypical 2-Cys Prx class, and a peroxiredoxin of the 1-Cys Prx class have been identified and partially characterized In our article we give an introduction to redox-based drug development strategies against protozoal parasites and summarize the present knowledge on peroxiredoxin systems in Plasmodium.
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PMID:Peroxiredoxin systems of protozoal parasites. 1808 96

All six mammalian peroxiredoxins are expressed in the lung. Peroxiredoxin (Prx) VI is the isoform expressed at the highest level and its lung expression exceeds that for other organs. The predominant location of Prx VI is the cytosol and acidic organelles of Clara cells of the conducting airways and type II epithelial cells and macrophages in the alveoli. Prx I and VI show developmental induction of transcription at birth. PrxVI shares structural homology with other peroxiredoxins exhibiting a thioredoxin fold and a conserved catalytic Cys residue in the N-terminus of the protein. This enzyme is highly inducible by oxidative stress in both the neonatal and adult lung consistent with a role in antioxidant defense. Prx VI has several properties that distinguish its peroxidase activity from other peroxiredoxins: it can reduce phospholipid hydroperoxides in addition to other organic hydroperoxides and H2O2; the electron donor that serves to reduce the oxidized peroxidatic cysteine is not thioredoxin but GSH; instead of homodimerization, heterodimerization with pi-glutathione S-transferase is required for regeneration of the active enzyme. Prx VI also expresses a phospholipase A2 activity that is Ca2+-independent, maximal at acidic pH, and dependent on a serine-based catalytic triad and nucleophilic elbow at the surface of the protein. Models of altered Prx VI expression at the cellular, organ and whole animal levels have demonstrated that Prx VI functions as an important anti-oxidant enzyme with levels of protection that exceed those ascribed to GSH peroxidase (GPx1). The phospholipase A2 activity plays an important role in lung surfactant homeostasis and is responsible for the bulk of the degradation of internalized phosphatidylcholine and its resynthesis by the reacylation pathway. Expression of peroxiredoxins is elevated in several lung diseases including lung cancer, mesothelioma and sarcoidosis, although the mechanism for these alterations is not known. The unique properties of Prx VI enable it to play an important role in lung cell function.
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PMID:Peroxiredoxins in the lung with emphasis on peroxiredoxin VI. 1808 1

Glutathione S-transferase pi has been shown to reactivate 1-cysteine peroxiredoxin (1-Cys Prx) by formation of a complex [L.A. Ralat, Y. Manevich, A.B. Fisher, R.F. Colman, Biochemistry 45 (2006) 360-372]. A model of the complex was proposed based on the crystal structures of the two enzymes. We have now characterized the complex of GST pi/1-Cys Prx by determining the M(w) of the complex, by measuring the catalytic activity of the GST pi monomer, and by identifying the interaction sites between GST pi and 1-Cys Prx. The M(w) of the purified GST pi/1-Cys Prx complex is 50,200 at pH 8.0 in the presence of 2.5mM glutathione, as measured by light scattering, providing direct evidence that the active complex is a heterodimer composed of equimolar amounts of the two proteins. In the presence of 4M KBr, GST pi is dissociated to monomer and retains catalytic activity, but the K(m) value for GSH is increased substantially. To identify the peptides of GST pi that interact with 1-Cys Prx, GST pi was digested with V8 protease and the peptides were purified. The binding by 1-Cys Prx of each of four pure GST pi peptides (residues 41-85, 115-124, 131-163, and 164-197) was investigated by protein fluorescence titration. An apparent stoichiometry of 1mol/subunit 1-Cys Prx was measured for each peptide and the formation of the heterodimer is decreased when these peptides are included in the incubation mixture. These results support our proposed model of the heterodimer.
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PMID:Characterization of the complex of glutathione S-transferase pi and 1-cysteine peroxiredoxin. 1835 25

The multifunctional, anti-Alzheimer drug, ladostigil (TV3326) [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate] combines the neuroprotective effects of the anti-Parkinson drug, rasagiline, a selective monoamine oxidase (MAO)-B inhibitor, with the cholinesterase (ChE) inhibitory activity of rivastigmine in a single molecule. Ladostigil has been shown to possess potent antiapoptotic and neuroprotective activities in various oxidative insults in vitro and in vivo, such as prevention of the fall in mitochondrial membrane potential and regulation of Bcl-2 family proteins. In the present study, we demonstrate that ladostigil (1 microM) increased cell viability, associated with the increase of catalase activity and decrease of intracellular reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells exposed to (hydrogen peroxide) H(2)O(2). Furthermore, ladostigil significantly elevated mRNA levels of the antioxidants enzymes, catalase, NAD(P)H quinone oxidoreductase 1 (NQO1) and peroxiredoxin 1 (Prx 1) in H(2)O(2)-treated SH-SY5Y cells. Chronic treatment with ladostigil (1 mg/kg gavage per day for 30 days) markedly up-regulated mRNA expression levels of various antioxidant enzymes in aged rat hippocampus (e.g. glutathione peroxidase precursor (GSHPX-P), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD)). These findings indicate that in addition to its multiple neuroprotective characteristics, ladostigil also possesses antioxidant properties, which might be beneficial for the treatment of oxidative stress (OS) in aging and age-associated neurodegenerative diseases.
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PMID:The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity. 1859 87

In this study, we compared royal jelly (RJ) produced by Apis mellifera ligustica and Apis cerana cerana in production, protein profiles, and abundances using proteomic approaches. The RJ proteome was displayed using two-dimensional gel electrophoresis (2DGE), and proteins were identified using MALDI-TOF MS and LC-Chip/ESI-QTOF MS. Differences in the RJ proteome between the two bee species were validated using western-blot analysis. RJ production by A. cerana cerana (3.21 +/- 0.43 g) is significantly lower than that of A. mellifera ligustica (80.5 +/- 7.83 g). The 2DGE based MS approach identified 52 and 60 proteins in the RJ of A. mellifera ligustica and A. cerana cerana, respectively. The majority of the identified proteins were major royal jelly proteins (MRJPs). Peroxiredoxin 2540, glutathione S-transferase S1, and MRJP5 were detected only in the RJ of A. mellifera ligustica, and MRJP1 was the most abundant MRJP. In contrast, MRJP7 was found only in the RJ of A. cerana cerana. But, similar to A. mellifera ligustica, MRJP1 was found most abundantly in this case too. In this study, glucose oxidase was identified for the first time in the A. cerana cerana RJ. Comparing the protein levels of MRJP1, 2, 3, 4, and 5 between the two species, they were significantly higher in the RJ of A. mellifera ligustica than in A. cerana cerana. This observation was supported by Western blot analysis using anti-MRJP1, 2, 3 antibodies. The result suggested that A. mellifera ligustica needs more nutrition to nurse the developing larvae and queens as compared to that of A. cerana cerana. This study improved our understanding of protein composition of RJ from Western and Eastern honeybees. RJ produced by A. mellifera ligustica exceeds the RJ from A. cerana cerana both in terms of production and health purposes.
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PMID:Royal jelly proteome comparison between A. mellifera ligustica and A. cerana cerana. 2030 72


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