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New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression

2020-10-21Journal article Open access
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dc.contributor.authorValério, Elisabete
dc.contributor.authorBarreiros, Sara
dc.contributor.authorRodrigues, Sara
dc.contributor.authorTurkina, Maria V.
dc.contributor.authorVasconcelos, Vitor M.
dc.contributor.authorCampos, Alexandre
dc.date.accessioned2021-04-08T10:31:45Z
dc.date.available2021-04-08T10:31:45Z
dc.date.issued2020-10-21
dc.descriptionThis article belongs to the Special Issue Advances in the Toxicity Mechanisms of Microcystins Revealed by Omics Approachespt_PT
dc.description.abstractMicrocystins (MCs) are hepatotoxins produced by some cyanobacteria. They are cyclic peptides that inhibit the serine/threonine protein phosphatases (PPs) PP1 and PP2A, especially PP2A. The inhibition of PP2A triggers a series of molecular events, which are responsible for most MC cytotoxic and genotoxic effects on animal cells. It is also known that MCs induce oxidative stress in cells due to the production of reactive oxygen species (ROS). However, a complete characterization of the toxic effects of MCs is still not accomplished. This study aimed to clarify additional molecular mechanisms involved in MC-LR toxicity, using Saccharomyces cerevisiae as eukaryotic model organism. First, a shotgun proteomic analysis of S. cerevisiae VL3 cells response to 1 nM, 10 nM, 100 nM, and 1 µM MC-LR was undertaken and compared to the control (cells not exposed to MC-LR). This analysis revealed a high number of proteins differentially expressed related with gene translation and DNA replication stress; oxidative stress; cell cycle regulation and carbohydrate metabolism. Inference of genotoxic effects of S. cerevisiae VL3 cells exposed to different concentrations of MC-LR were evaluated by analyzing the expression of genes Apn1, Apn2, Rad27, Ntg1, and Ntg2 (from the Base Excision Repair (BER) DNA repair system) using the Real-Time RT-qPCR technique. These genes displayed alterations after exposure to MC-LR, particularly the Apn1/Apn2/Rad27, pointing out effects of MC-LR in the Base Excision Repair system (BER). Overall, this study supports the role of oxidative stress and DNA replication stress as important molecular mechanisms of MC-LR toxicity. Moreover, this study showed that even at low-concentration, MC-LR can induce significant changes in the yeast proteome and in gene expression.pt_PT
dc.description.abstractKey Contribution: The results of this study reveal molecular mechanisms of MC-LR toxicity in yeast related with the production of ROS, oxidative stress, and genotoxicity.pt_PT
dc.description.sponsorshipThis research was funded by the European Regional Development Fund (ERDF) through the COMPETE e Operational Competitiveness Program and national funds through FCT (Foundation for Science and Technology) grant to E. Valerio (SFRH/BPD/75922/2011). It was also funded by the Strategic Funding UIDB/04423/2020 and UIDP/04423/2020 through national funds provided by FCT—Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the program PT2020. This work has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 823860 (TOXICROP).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationToxins (Basel). 2020 Oct 21;12(10):667. doi: 10.3390/toxins12100667.pt_PT
dc.identifier.doi10.3390/toxins12100667pt_PT
dc.identifier.issn2072-6651
dc.identifier.urihttp://hdl.handle.net/10400.18/7666
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation823860pt_PT
dc.relationMULTIDISCIPLINARY APPROACH FOR THE SEARCH OF BIOMARKERS TO DETECT CYTOTOXIC AND GENOTOXIC EFFECTS CAUSED BY MICROCYSTINS
dc.relationInterdisciplinary Centre of Marine and Environmental Research
dc.relationInterdisciplinary Centre of Marine and Environmental Research
dc.relation.publisherversionhttps://www.mdpi.com/2072-6651/12/10/667pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBER Genespt_PT
dc.subjectMTT Assays; Microcystin-LRpt_PT
dc.subjectReal-Time RT-qPCRpt_PT
dc.subjectSaccharomyces cerevisiaept_PT
dc.subjectShotgun Proteomicspt_PT
dc.subjectAgentes Microbianos e Ambiente
dc.titleNew Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expressionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMULTIDISCIPLINARY APPROACH FOR THE SEARCH OF BIOMARKERS TO DETECT CYTOTOXIC AND GENOTOXIC EFFECTS CAUSED BY MICROCYSTINS
oaire.awardTitleInterdisciplinary Centre of Marine and Environmental Research
oaire.awardTitleInterdisciplinary Centre of Marine and Environmental Research
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F75922%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04423%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04423%2F2020/PT
oaire.citation.issue10pt_PT
oaire.citation.startPage667pt_PT
oaire.citation.titleToxinspt_PT
oaire.citation.volume12pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationc3a27ebb-247c-4198-a83d-e8ca3e9af0f3
relation.isProjectOfPublicatione47e16ab-4259-4ce8-af09-551f7f31443a
relation.isProjectOfPublicationc3064e67-096b-442c-b636-ae0e2da784a3
relation.isProjectOfPublication.latestForDiscoverye47e16ab-4259-4ce8-af09-551f7f31443a

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