Pedroso, NunoGomes Alves, PatriciaMarinho, H. SusanaBrito, VeronicaBoada, CristinaAntunes, FernandoHerrero, EnriquePenque, DeborahCyrne, Luísa2013-02-122013-02-122012-10Free Radic Res. 2012 Oct;46(10):1267-79. Epub 2012 Jul 161071-5762doi: 10.3109/10715762.2012.704997http://hdl.handle.net/10400.18/1283n Saccharomyces cerevisiae, adaptation to hydrogen peroxide (H₂O₂) decreases plasma membrane permeability to H₂O₂, changes its lipid composition and reorganizes ergosterol-rich microdomains by a still unknown mechanism. Here we show, by a quantitative analysis of the H₂O₂-induced adaptation effect on the S. cerevisiae plasma membrane-enriched fraction proteome, using two-dimensional gel electrophoresis, that 44 proteins are differentially expressed. Most of these proteins were regulated at a post-transcriptional level. Fourteen of these proteins contain redox-sensitive cysteine residues and nine proteins are associated with lipid and vesicle traffic. In particular, three proteins found in eisosomes and in the eisosome-associated membrane compartment occupied by Can1p were up-regulated (Pil1p, Rfs1p and Pst2p) during adaptation to H₂O₂. Survival studies after exposure to lethal H₂O₂ doses using yeast strains bearing a gene deletion corresponding to proteins associated to lipid and vesicle traffic demonstrated for the first time that down-regulation of Kes1p, Vps4p and Ynl010wp and up-regulation of Atp1 and Atp2 increases resistance to H₂O₂. Moreover, for the pil1Δ strain, H₂O₂ at low levels produces a hormetic effect by increasing proliferation. In conclusion, these data further confirms the plasma membrane as an active cellular site during adaptation to H₂O₂ and shows that proteins involved in lipid and vesicle traffic are important mediators of H₂O₂ adaptation.engProteomicsGenómica Funcional e EstruturalEisosomesMembrane Compartment of Can1pOxidative StressPlasma Membrane PermeabilityLipid Trafficjournal article