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

Detalhes bibliográficos
Autor(a) principal: Valério, Elisabete
Data de Publicação: 2020
Outros Autores: Barreiros, Sara, Rodrigues, Sara, Turkina, Maria V., Vasconcelos, Vitor M., Campos, Alexandre
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/7666
Resumo: This article belongs to the Special Issue Advances in the Toxicity Mechanisms of Microcystins Revealed by Omics Approaches
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spelling New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene ExpressionBER GenesMTT Assays; Microcystin-LRReal-Time RT-qPCRSaccharomyces cerevisiaeShotgun ProteomicsAgentes Microbianos e AmbienteThis article belongs to the Special Issue Advances in the Toxicity Mechanisms of Microcystins Revealed by Omics ApproachesMicrocystins (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.Key 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.This 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).MDPIRepositório Científico do Instituto Nacional de SaúdeValério, ElisabeteBarreiros, SaraRodrigues, SaraTurkina, Maria V.Vasconcelos, Vitor M.Campos, Alexandre2021-04-08T10:31:45Z2020-10-212020-10-21T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/7666engToxins (Basel). 2020 Oct 21;12(10):667. doi: 10.3390/toxins12100667.2072-665110.3390/toxins12100667info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:42:08Zoai:repositorio.insa.pt:10400.18/7666Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:42:18.708933Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression
title New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression
spellingShingle New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression
Valério, Elisabete
BER Genes
MTT Assays; Microcystin-LR
Real-Time RT-qPCR
Saccharomyces cerevisiae
Shotgun Proteomics
Agentes Microbianos e Ambiente
title_short New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression
title_full New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression
title_fullStr New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression
title_full_unstemmed New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression
title_sort New Insights in Saccharomyces cerevisiae Response to the Cyanotoxin Microcystin-LR, Revealed by Proteomics and Gene Expression
author Valério, Elisabete
author_facet Valério, Elisabete
Barreiros, Sara
Rodrigues, Sara
Turkina, Maria V.
Vasconcelos, Vitor M.
Campos, Alexandre
author_role author
author2 Barreiros, Sara
Rodrigues, Sara
Turkina, Maria V.
Vasconcelos, Vitor M.
Campos, Alexandre
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Valério, Elisabete
Barreiros, Sara
Rodrigues, Sara
Turkina, Maria V.
Vasconcelos, Vitor M.
Campos, Alexandre
dc.subject.por.fl_str_mv BER Genes
MTT Assays; Microcystin-LR
Real-Time RT-qPCR
Saccharomyces cerevisiae
Shotgun Proteomics
Agentes Microbianos e Ambiente
topic BER Genes
MTT Assays; Microcystin-LR
Real-Time RT-qPCR
Saccharomyces cerevisiae
Shotgun Proteomics
Agentes Microbianos e Ambiente
description This article belongs to the Special Issue Advances in the Toxicity Mechanisms of Microcystins Revealed by Omics Approaches
publishDate 2020
dc.date.none.fl_str_mv 2020-10-21
2020-10-21T00:00:00Z
2021-04-08T10:31:45Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/7666
url http://hdl.handle.net/10400.18/7666
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxins (Basel). 2020 Oct 21;12(10):667. doi: 10.3390/toxins12100667.
2072-6651
10.3390/toxins12100667
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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