title: The glutathione system of Aspergillus nidulans involves a fungus-specific glutathione S-transferase.
abstract: The tripeptide glutathione is involved in cellular defense mechanisms for xenobiotics and reactive oxygen species. This study investigated glutathione-dependent mechanisms in the model organism Aspergillus nidulans. A recombinant dimeric protein of A. nidulans glutathione reductase (GR) contained FAD and reduced oxidized glutathione (GSSG) using NADPH as an electron donor. A deletion strain of the GR gene (glrA) accumulated less intracellular reduced glutathione (GSH), indicating that the fungal GR contributes to GSSG reduction in vivo. Growth of the deletion strain of glrA was temperature-sensitive, and this phenotype was suppressed by adding GSH to the medium. The strain subsequently accumulated more intracellular superoxide, and cell-free respiration activity was partly defective. Growth of the strain decreased in the presence of oxidants, which induced glrA expression 1.5-6-fold. These results indicated that the fungal glutathione system functions as an antioxidant mechanism in A. nidulans. Our findings further revealed an initial proteomic differential display on GR-depleted and wild type strains. Up-regulation of thioredoxin reductase, peroxiredoxins, catalases, and cytochrome c peroxidase in the glrA-deletion strain revealed interplay between the glutathione system and both the thioredoxin system and hydrogen peroxide defense mechanisms. We also identified a hypothetical, up-regulated protein in the GR-depleted strains as glutathione S-transferase, which is unique among Ascomycetes fungi.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sato
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Shimizu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Naoki
authors.initials: N
authors.lastname: Takaya
mesh_terms: D001233:Aspergillus nidulans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000502:physiology*; D005800:Genes, Fungal; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009249:NADP / Q000737:chemistry / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010088:Oxidoreductases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D015262:Xenobiotics; D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D005982:Glutathione Transferase; D005978:Glutathione