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Kenan Gumustekin - One of the best experts on this subject based on the ideXlab platform.

  • effects of nicotine and vitamin e on Glutathione Reductase activity in some rat tissues in vivo and in vitro
    European Journal of Pharmacology, 2007
    Co-Authors: Mustafa Erat, Mehmet Ciftci, Kenan Gumustekin
    Abstract:

    Abstract Effects of nicotine, and nicotine + vitamin E on Glutathione Reductase (Glutathione: NADP+ oxidoReductase, EC 1.8.1.7) activity in the muscle, heart, lungs, testicles, kidney, stomach, brain and liver tissues were investigated in vivo and also in vitro. The groups were: nicotine [0.5 mg/kg/day, intraperitoneal (i.p.)]; nicotine + vitamin E [75 mg/kg/day, intragastric (i.g.)]; and control group (receiving only vehicles). There were eight rats per group and supplementation period was 3 weeks. The results showed that nicotine (0.5 mg/kg, i.p.) inhibited Glutathione Reductase activity significantly in the liver, lungs, heart, stomach, kidney, and testicles by ∼ 61.5%, ∼ 65%, ∼ 70.5%, ∼ 72.5%, ∼ 64% and ∼ 71.5%, respectively, while it had activated Glutathione Reductase activity in the brain by ∼ 11.8%, and had no effect on the muscle Glutathione Reductase activity. Vitamin E supplementation prevented this nicotine-induced decrease in Glutathione Reductase activity in liver, lungs, heart, stomach, and kidney. However, it did not prevent this nicotine-induced decrease in testicles. In vitro studies were also carried out to elucidate the effects of nicotine and vitamin E on Glutathione Reductase activity. In vitro results correlated well with in vivo experimental results in liver, lungs, heart, stomach, and testicular tissues. These results show that vitamin E administration generally restores the inactivation of Glutathione Reductase activity due to nicotine administration in various rat tissues in vivo, and also in vitro.

Anthony Cerami - One of the best experts on this subject based on the ideXlab platform.

  • engineering the substrate specificity of Glutathione Reductase toward that of trypanothione reduction
    Proceedings of the National Academy of Sciences of the United States of America, 1991
    Co-Authors: Graeme B Henderson, Nicholas J Murgolo, John Kuriyan, Klara Osapay, Dorothea Kominos, Alan Berry, Nigel S Scrutton, Nigel W Hinchliffe, Richard N Perham, Anthony Cerami
    Abstract:

    Abstract Glutathione Reductase (EC 1.6.4.2; CAS registry number 9001-48-3) and trypanothione Reductase (CAS registry number 102210-35-5), which are related flavoprotein disulfide oxidoReductases, have marked specificities for Glutathione and trypanothione, respectively. A combination of primary sequence alignments and molecular modeling, together with the high-resolution crystal structure of human Glutathione Reductase, identified certain residues as potentially being responsible for substrate discrimination. Site-directed mutagenesis of Escherichia coli Glutathione Reductase was used to test these predictions. The mutation of Asn-21 to Arg demonstrated that this single change was insufficient to generate the greater discrimination against trypanothione shown by human Glutathione Reductase compared with the E. coli enzyme. However, the mutation of Ala-18, Asn-21, and Arg-22 to the amino acid residues (Glu, Trp, and Asn, respectively) in corresponding positions in Trypanosoma congolense trypanothione Reductase confirmed that this region of polypeptide chain is intimately involved in substrate recognition. It led to a mutant form of E. coli Glutathione Reductase that possessed essentially no activity with Glutathione but that was able to catalyze trypanothione reduction with a kcat/Km value that was 10% of that measured for natural trypanothione Reductases. These results should be of considerable importance in the design of trypanocidal drugs targeted at the differences between Glutathione and trypanothione metabolism in trypanosomatids and their hosts.

Narciso Couto - One of the best experts on this subject based on the ideXlab platform.

  • the role of Glutathione Reductase and related enzymes on cellular redox homoeostasis network
    Free Radical Biology and Medicine, 2016
    Co-Authors: Narciso Couto, Jennifer Wood, Jill Barber
    Abstract:

    Abstract In this review article we examine the role of Glutathione Reductase in the regulation, modulation and maintenance of cellular redox homoeostasis. Glutathione Reductase is responsible for maintaining the supply of reduced Glutathione; one of the most abundant reducing thiols in the majority of cells. In its reduced form, Glutathione plays key roles in the cellular control of reactive oxygen species. Reactive oxygen species act as intracellular and extracellular signalling molecules and complex cross talk between levels of reactive oxygen species, levels of oxidised and reduced Glutathione and other thiols, and antioxidant enzymes such as Glutathione Reductase determine the most suitable conditions for redox control within a cell or for activation of programmed cell death. Additionally, we discuss the translation and expression of Glutathione Reductase in a number of organisms including yeast and humans. In yeast and human cells, a single gene expresses more than one form of Glutathione Reductase, destined for residence in the cytoplasm or for translocation to different organelles; in plants, however, two genes encoding this protein have been described. In general, insects and kinetoplastids (a group of protozoa, including Plasmodia and Trypanosoma) do not express Glutathione Reductase or Glutathione biosynthetic enzymes. Instead, they express either the thioredoxin system or the trypanothione system. The thioredoxin system is also present in organisms that have the Glutathione system and there may be overlapping functions with cross-talk between the two systems. Finally we evaluate therapeutic targets to overcome oxidative stress associated cellular disorders.

J Barrett - One of the best experts on this subject based on the ideXlab platform.

  • the purification and properties of Glutathione Reductase from the cestode moniezia expansa
    The International Journal of Biochemistry & Cell Biology, 1995
    Co-Authors: Mora J Mccallum, J Barrett
    Abstract:

    Abstract Glutathione Reductase has a central role in Glutathione metabolism and as such is a potential target for chemotherapy. The aim of the work was to purify and characterise Glutathione Reductase from the cestode Moniezia expansa and to compare the properties of the helminth enzyme with its mammalian counterpart. The enzyme was purified by a combination of anion exchange and affinity chromatography and further characterized by chromatofocusing and gel electrophoresis. Analysis revealed a single isoenzyme of Glutathione Reductase in Moniezia expansa, with a pI of 5.8. The enzyme was a homodimer of native molecular weight 114 kDa, subunit weight 63 kDa. Enzyme activity was affected by buffer concentration and the presence of monovalent sodium salts. The pH optimum was 7.4 with NADPH as cofactor and 5 with NADH. The Kma for oxidized Glutathione was 76 μM and for NADPH and NADH, 21 and 350 μM respectively. In addition to oxidized Glutathione only the mixed disulphide between CoA and Glutathione (CoASSG) showed any significant activity as substrate. The cestode enzyme was inhibited by a variety of compounds including arsonic derivatives, 2,4,6 trinitrobenzene sulfonate 1,3-bis (2-chlorethyl)-1-nitrosourea and oxidized Glutathione. In conclusion the Glutathione Reductase of M. expansa resembles the mammalian enzyme in its general physical properties and its substrate and inhibitor profile. However, the parasite enzyme shows an unusually high activity with the mixed disulphide of coenzyme A and Glutathione (CoASSG) and appears to be more sensitive to inhibition by sodium ions.

Rajindar S. Sohal - One of the best experts on this subject based on the ideXlab platform.

  • overexpression of Glutathione Reductase extends survival in transgenic drosophila melanogaster under hyperoxia but not normoxia
    The FASEB Journal, 1999
    Co-Authors: Robin J Mockett, Rajindar S. Sohal
    Abstract:

    The purpose of this study was to test the hypothesis that overexpression of Glutathione Reductase in transgenic Drosophila melanogaster increases resistance to oxidative stress and retards the aging process. Transgenic flies were generated by microinjection and subsequent mobilization of a P element construct containing the genomic Glutathione Reductase gene of Drosophila, with 4 kb upstream and 1.5 kb downstream of the coding region. Transgenic animals stably overexpressed Glutathione Reductase by up to 100% throughout adult life and under continuous exposure to 100% oxygen or air. Under hyperoxic conditions, overexpressors had increased longevity, decreased accrual of protein carbonyls, and dramatically increased survival rates after recovery from a semi-lethal dose of 100% oxygen. Under normoxic conditions, overexpression of Glutathione Reductase had no effect on longevity, protein carbonyl content, reduced Glutathione, or Glutathione disulfide content, although the total consumption of oxygen was slig...

  • Molecular Organization of the Glutathione Reductase Gene inDrosophila melanogaster
    Archives of Biochemistry and Biophysics, 1997
    Co-Authors: Mehmet Candas, Rajindar S. Sohal, Svetlana N. Radyuk, Vladimir I. Klichko
    Abstract:

    Glutathione Reductase catalyzes the conversion of the oxidized form of Glutathione to regenerate reduced Glutathione, which acts as a versatile intracellular reductant. The present study provides initial characterization of the Glutathione Reductase gene inDrosophila melanogasterand its response to experimentally induced oxidative stress.DrosophilacDNA clones were isolated, based on cross-hybridization to theMusca domesticaGlutathione Reductase cDNA. Genomic clones were isolated by cross-hybridization with theDrosophilacDNA as hybridization probe. Northern analysis of adultDrosophilapoly(A)+RNA, utilizing theDrosophilacDNA probe, revealed a hybridization signal in the 2-kb range. The entire sequence of one cDNA was determined. In addition to a coding domain of 1431 bases, the sequence included 206 bases upstream of a putative start codon and 355 bases downstream of a putative stop codon. Based on the cDNA sequence, the 476 amino acid sequence of theDrosophilaGlutathione Reductase gene was deduced and was found to have extensive similarities with the Glutathione Reductase gene from other species. Gene mapping of a 13-kb genomic fragment revealed that the Glutathione Reductase gene consists of at least two exons spanning approximately 5 kb. A first exon contains sequence for only the first 5 amino acids and the first base of the sixth and appears to be separated by a ca. 2.5-kb intron from the remainder of the coding region, which is confined to