title: The role of two putative nitroreductases, Frm2p and Hbn1p, in the oxidative stress response in Saccharomyces cerevisiae.
abstract: The nitroreductase family is comprised of a group of FMN- or FAD-dependent enzymes that are able to metabolize nitrosubstituted compounds using the reducing power of NAD(P)H. These nitroreductases can be found in bacterial species and, to a lesser extent, in eukaryotes. There is little information on the biochemical functions of nitroreductases. Some studies suggest their possible involvement in the oxidative stress response. In the yeast Saccharomyces cerevisiae, two nitroreductase proteins, Frm2p and Hbn1p, have been described. While Frm2p appears to act in the lipid signalling pathway, the function of Hbn1p is completely unknown. In order to elucidate the functions of Frm2p and Hbn1p, we evaluated the sensitivity of yeast strains, proficient and deficient in both oxidative stress proteins, for respiratory competence, antioxidant-enzyme activities, intracellular reactive oxygen species (ROS) production and lipid peroxidation. We found reduced basal activity of superoxide dismutase (SOD), ROS production, lipid peroxidation and petite induction and higher sensitivity to 4-nitroquinoline-oxide (4-NQO) and N-nitrosodiethylamine (NDEA), as well as higher basal activity of catalase (CAT) and glutathione peroxidase (GPx) and reduced glutathione (GSH) content in the single and double mutant strains frm2Delta and frm2Delta hbn1Delta. These strains exhibited less ROS accumulation and lipid peroxidation when exposed to peroxides, H(2)O(2) and t-BOOH. In summary, the Frm1p and Hbn1p nitroreductases influence the response to oxidative stress in S. cerevisae yeast by modulating the GSH contents and antioxidant enzymatic activities, such as SOD, CAT and GPx.
authors.affiliation: Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av Bento Gonçalves 9500, 91507-970 Porto Alegre, RS, Brazil.
authors.forename: Iuri Marques
authors.initials: IM
authors.lastname: de Oliveira
authors.forename: Alfeu
authors.initials: A
authors.lastname: Zanotto-Filho
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.forename: Diego
authors.initials: D
authors.lastname: Bonatto
authors.forename: João Antonio Pêgas
authors.initials: JA
authors.lastname: Henriques
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004052:Diethylnitrosamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation; D009154:Mutation; D009601:Nitroreductases / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D004052:Diethylnitrosamine; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C548067:FRM2 protein, S cerevisiae; C548068:HBN1 protein, S cerevisiae; D009601:Nitroreductases; D005978:Glutathione