title: Citrinin-induced fluidization of the plasma membrane of the fission yeast Schizosaccharomyces pombe.
abstract: Citrinin (CTN) is a toxic fungal metabolite that is a hazardous contaminant of foods and feeds. In the present study, its acute toxicity and effects on the plasma membrane of Schizosaccharomyces pombe were investigated. The minimum inhibitory concentration of CTN against the yeast cells proved to be 500 μM. Treatment with 0, 250, 500 or 1000 μM CTN for 60 min resulted in a 0%, 2%, 21% or 100% decrease, respectively, in the survival rate of the cell population. Treatment of cells with 0, 100, 500 or 1000 μM CTN for 20 min induced decrease in the phase-transition temperature of the 5-doxylstearic acid-labeled plasma membrane to 16.51, 16.04, 14.18 or 13.98°C, respectively as measured by electron paramagnetic resonance spectroscopy. This perturbation was accompanied by the efflux of essential K⁺ from the cells. The existence of an interaction between CTN and glutathione was detected for the first time by spectrofluorometry. Our observations may suggest a direct interaction of CTN with the free sulfhydryl groups of the integral proteins of the plasma membrane, leading to dose-dependent membrane fluidization. The change in fluidity disturbed the ionic homeostasis, contributing to the death of the cells, which is a novel aspect of CTN cytotoxicity.
authors.affiliation: Institute of Bioanalysis, Faculty of Medicine, University of Pécs, Pécs, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Blaskó
authors.forename: Nóra
authors.initials: N
authors.lastname: Mike
authors.forename: Pál
authors.initials: P
authors.lastname: Gróf
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Gazdag
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Czibulya
authors.forename: Lívia
authors.initials: L
authors.lastname: Nagy
authors.forename: Sándor
authors.initials: S
authors.lastname: Kunsági-Máté
authors.forename: Miklós
authors.initials: M
authors.lastname: Pesti
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D002463:Cell Membrane Permeability; D002953:Citrinin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D011188:Potassium / Q000032:analysis / Q000378:metabolism; D011523:Protoplasts / Q000737:chemistry / Q000187:drug effects; D012568:Schizosaccharomyces / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D013050:Spectrometry, Fluorescence; D044366:Transition Temperature / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D002953:Citrinin; D005978:Glutathione; D011188:Potassium
keywords: 5-SASL; 5-doxylstearic acid; CTN; Citrinin; EPR; GSH; Glutathione; MIC; OD; PAT; Plasma membrane; ROS; S; S. pombe; SM; Schizosaccharomyces pombe; citrinin; electron paramagnetic resonance; glutathione; hyperfine splitting constant; minimal liquid medium; minimum inhibitory concentration; optical density; order parameter; patulin; reactive oxygen species