title: Regulation of cytotoxic, non-estrogenic, oxidative stress-induced processes of zearalenone in the fission yeast Schizosaccharomyces pombe.
abstract: This study investigates the non-estrogenic mode of zearalenone (ZEA) toxicity in a novel aspect via accumulation of reactive oxygen species (ROS) and the regulation of the activities of antioxidant enzymes in the Schizosaccharomyces pombe in acute toxicity tests. In comparison with the control, 500 μM ZEA treatment caused 66% decrease in the concentration of glutathione (GSH), which was a consequence, in the absence of ZEA-GSH interaction, of the GSH-consuming processes of the antioxidant system; this depletion of GSH initiated a 1.8- and 2.0-fold accumulation of the superoxide anion and hydrogen peroxide, but did not increase the concentration of the hydroxyl radical; ROS-induced adaptation processes via activation of the Pap1 transcription factor resulted in significantly increased activities of superoxide dismutases, catalase, glutathione reductase and glutathione S-transferase, and decreased activities of glutathione peroxidase and glucose-6-phosphate dehydrogenase. This treatment altered the sterol composition of the cells by inducing decreased concentrations of ergosterol, squalene and 24-methylene-24,25-hydrolanosterol, and also elevated the number of fragmented nuclei. Cells strived to correct the unbalanced redox state by regulation of the antioxidant system, but this was not enough to defend the cells from the disturbed sterol composition, the cell cycle arrest, and the fragmentation of nuclei.
authors.affiliation: Department of General and Environmental Microbiology, Faculty of Sciences, University of Pécs, P.O. Box 266, Pécs H-7602, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Mike
authors.forename: Gábor
authors.initials: G
authors.lastname: Papp
authors.forename: Milan
authors.initials: M
authors.lastname: Certik
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Czibulya
authors.forename: Sándor
authors.initials: S
authors.lastname: Kunsági-Máté
authors.forename: István
authors.initials: I
authors.lastname: Ember
authors.forename: Csaba
authors.initials: C
authors.lastname: Vágvölgyi
authors.forename: Miklós
authors.initials: M
authors.lastname: Pesti
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Gazdag
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D000073718:Pancreatitis-Associated Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D023382:Toxicity Tests, Acute; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D017382:Reactive Oxygen Species; D013261:Sterols; D013481:Superoxides; D015025:Zearalenone; D006861:Hydrogen Peroxide; D005978:Glutathione
keywords: 2,7-dichlorodihydrofluorescein diacetate; 4′,6-diamidino-2-phenylindole; C. albicans; CAT; Candida albicans; DAPI; DCHF-DA; EBP; EPR; ER; Ergosterol; G6PD; GPx; GR; GSH; GSSG; GST; Glutathione; H(2)O(2); MAPK; MIC; N-tert-butyl-α-phenylnitrone; O(2)(•−); OH; Oxidative stress; PAT; PBN; ROS; Regulation; S. cerevisiae; S. pombe; SOD; Saccharomyces cerevisiae; Schizosaccharomyces pombe; ZEA; Zearalenone; catalase; electron paramagnetic resonance; estrogen receptor; estrogen-binding protein; glucose-6-phosphate dehydrogenase; glutathione; glutathione S-transferase; glutathione disulfide; glutathione peroxidase; glutathione reductase; hydrogen peroxide; hydroxyl radical; minimal inhibitory concentration; mitogen-activated protein kinase; patulin; reactive oxygen species; superoxide anion; superoxide dismutase; zearalenone