Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress

Detalhes bibliográficos
Autor(a) principal: Avelar, Lívia das Graças Amaral
Data de Publicação: 2019
Outros Autores: Gava, Sandra Grossi, Neves, Renata Heisler, Silva, Mercedes Carolina Soares, Pereira, Neusa Araújo, Tavares, Naiara Clemente, El Khal, Assmaa, Mattos, Ana Carolina Alves de, Silva, José Roberto Machado, Oliveira, Guilherme Corrêa de, Mourão, Marina de Moraes
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/37197
Resumo: Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
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spelling Avelar, Lívia das Graças AmaralGava, Sandra GrossiNeves, Renata HeislerSilva, Mercedes Carolina SoaresPereira, Neusa AraújoTavares, Naiara ClementeEl Khal, AssmaaMattos, Ana Carolina Alves deSilva, José Roberto MachadoOliveira, Guilherme Corrêa deMourão, Marina de Moraes2019-11-20T14:04:25Z2019-11-20T14:04:25Z2019AVELAR, Lívia das Graças Amaral et al. Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress. Frontiers in Immunology, v. 10, p. 1-16, 2019.1664-3224https://www.arca.fiocruz.br/handle/icict/3719710.3389/fimmu.2019.000211664-3224engFrontiers Research FoundationSmp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stressinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Rio de Janeiro, RJ, Brasil.Instituto Tecnológico Vale. Belém, PA, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Eukaryotic protein kinases (ePKs) are good medical targets for drug development in different biological systems. ePKs participate in many cellular processes, including the p38 MAPK regulation of homeostasis upon oxidative stress. We propose to assess the role of Smp38 MAPK signaling pathway in Schistosoma mansoni development and protection against oxidative stress, parasite survival, and also to elucidate which target genes have their expression regulated by Smp38 MAPK. After a significant reduction of up to 84% in the transcription level by Smp38 MAPK gene knockdown, no visible phenotypic changes were reported in schistosomula in culture. The development of adult worms was tested in vivo in mice infected with the Smp38 knocked-down schistosomula. It was observed that Smp38 MAPK has an essential role in the transformation and survival of the parasites as a low number of adult worms was recovered. Smp38 knockdown also resulted in decreased egg production, damaged adult worm tegument, and underdeveloped ovaries in females. Furthermore, only ~13% of the eggs produced developed into mature eggs. Our results suggest that inhibition of the Smp38 MAPK activity interfere in parasites protection against reactive oxygen species. Smp38 knockdown in adult worms resulted in 80% reduction in transcription levels on the 10th day, with consequent reduction of 94.4% in oviposition in vitro. In order to search for Smp38 MAPK pathway regulated genes, we used an RNASeq approach and identified 1,154 DEGs in Smp38 knockdown schistosomula. A substantial proportion of DEGs encode proteins with unknown function. The results indicate that Smp38 regulates essential signaling pathways for the establishment of parasite homeostasis, including genes related to antioxidant defense, structural composition of ribosomes, spliceosomes, cytoskeleton, as well as, purine and pyrimidine metabolism pathways. Our data show that the Smp38 MAPK signaling pathway is a critical route for parasite development and may present attractive therapeutic targets for the treatment and control of schistosomiasis.Schistosoma mansoniDevelopmentGene expressionOvipositionOxidative stressp38 MAPKSignaling pathwaysinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/37197/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALSmp38 MAP Kinase Regulation in.pdfSmp38 MAP Kinase Regulation in.pdfapplication/pdf3524567https://www.arca.fiocruz.br/bitstream/icict/37197/2/Smp38%20MAP%20Kinase%20Regulation%20in.pdfb006a303b3f1cc9b4d0990aae232e38aMD52TEXTSmp38 MAP Kinase Regulation in.pdf.txtSmp38 MAP Kinase Regulation in.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress
title Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress
spellingShingle Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress
Avelar, Lívia das Graças Amaral
Schistosoma mansoni
Development
Gene expression
Oviposition
Oxidative stress
p38 MAPK
Signaling pathways
title_short Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress
title_full Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress
title_fullStr Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress
title_full_unstemmed Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress
title_sort Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress
author Avelar, Lívia das Graças Amaral
author_facet Avelar, Lívia das Graças Amaral
Gava, Sandra Grossi
Neves, Renata Heisler
Silva, Mercedes Carolina Soares
Pereira, Neusa Araújo
Tavares, Naiara Clemente
El Khal, Assmaa
Mattos, Ana Carolina Alves de
Silva, José Roberto Machado
Oliveira, Guilherme Corrêa de
Mourão, Marina de Moraes
author_role author
author2 Gava, Sandra Grossi
Neves, Renata Heisler
Silva, Mercedes Carolina Soares
Pereira, Neusa Araújo
Tavares, Naiara Clemente
El Khal, Assmaa
Mattos, Ana Carolina Alves de
Silva, José Roberto Machado
Oliveira, Guilherme Corrêa de
Mourão, Marina de Moraes
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Avelar, Lívia das Graças Amaral
Gava, Sandra Grossi
Neves, Renata Heisler
Silva, Mercedes Carolina Soares
Pereira, Neusa Araújo
Tavares, Naiara Clemente
El Khal, Assmaa
Mattos, Ana Carolina Alves de
Silva, José Roberto Machado
Oliveira, Guilherme Corrêa de
Mourão, Marina de Moraes
dc.subject.en.pt_BR.fl_str_mv Schistosoma mansoni
Development
Gene expression
Oviposition
Oxidative stress
p38 MAPK
Signaling pathways
topic Schistosoma mansoni
Development
Gene expression
Oviposition
Oxidative stress
p38 MAPK
Signaling pathways
description Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-11-20T14:04:25Z
dc.date.available.fl_str_mv 2019-11-20T14:04:25Z
dc.date.issued.fl_str_mv 2019
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.citation.fl_str_mv AVELAR, Lívia das Graças Amaral et al. Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress. Frontiers in Immunology, v. 10, p. 1-16, 2019.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/37197
dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
dc.identifier.doi.pt_BR.fl_str_mv 10.3389/fimmu.2019.00021
dc.identifier.eissn.none.fl_str_mv 1664-3224
identifier_str_mv AVELAR, Lívia das Graças Amaral et al. Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress. Frontiers in Immunology, v. 10, p. 1-16, 2019.
1664-3224
10.3389/fimmu.2019.00021
url https://www.arca.fiocruz.br/handle/icict/37197
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/37197/1/license.txt
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