title: The role of glutathione reductase and related enzymes on cellular redox homoeostasis network.
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.
authors.affiliation: Michael Barber Centre for Mass Spectrometry, Manchester Institute of Biotechnology, University of Manchester, Princess Road, Manchester M1 7DN, UK; ChELSI Institute, Department of Chemical and Biological Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD, UK. Electronic address: n.couto@sheffield.ac.uk.
authors.forename: Narciso
authors.initials: N
authors.lastname: Couto
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wood
authors.affiliation: Michael Barber Centre for Mass Spectrometry, Manchester Institute of Biotechnology, University of Manchester, Princess Road, Manchester M1 7DN, UK; Manchester Pharmacy School, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Barber
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase
keywords: Glutathione; Glutathione reductase; Oxidative stress; Reactive oxygen species; Redox homoeostasis