Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets

Detalhes bibliográficos
Autor(a) principal: Lancelot, Julien
Data de Publicação: 2013
Outros Autores: Caby, Stephanie, Dubois-Abdesselem, Florence, Vanderstraete, Mathieu, Trolet, Jacques, Oliveira, Guilherme Corrêa de, Bracher, Franz, Jung, Manfred, Pierce, Raymond John
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/29916
Resumo: Center for Infection and Immunity of Lille. Universite Lille Nord de France. Institut Pasteur de Lille. Lille, France
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spelling Lancelot, JulienCaby, StephanieDubois-Abdesselem, FlorenceVanderstraete, MathieuTrolet, JacquesOliveira, Guilherme Corrêa deBracher, FranzJung, ManfredPierce, Raymond John2018-11-07T12:36:09Z2018-11-07T12:36:09Z2013LANCELOT, Julien et al. Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets. PLoS Negl Trop Dis., v. 7, n. 9, e2428, 2013.1935-2727https://www.arca.fiocruz.br/handle/icict/2991610.1371/journal.pntd.0002428engPublic Library of ScienceEsquistossomosedrogasschistosomiasisdrugsSchistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targetsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCenter for Infection and Immunity of Lille. Universite Lille Nord de France. Institut Pasteur de Lille. Lille, FranceCenter for Infection and Immunity of Lille. Universite Lille Nord de France. Institut Pasteur de Lille. Lille, FranceCenter for Infection and Immunity of Lille. Universite Lille Nord de France. Institut Pasteur de Lille. Lille, FranceCenter for Infection and Immunity of Lille. Universite Lille Nord de France. Institut Pasteur de Lille. Lille, FranceCenter for Infection and Immunity of Lille. Universite Lille Nord de France. Institut Pasteur de Lille. Lille, FranceFundacao Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Grupo de Genômica e Biologia Computacional. Centro de Excelência em Bioinformática. Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, BrazilDepartment fur Pharmazie. Zentrum fur Pharmaforschung. Ludwig-Maximilians-Universitat. Munchen, GermanyInstitut fur Pharmazeutische Wissenschaften. Albert-Ludwigs-Universitat Freiburg. Freiburg, GermanyCenter for Infection and Immunity of Lille. Universite Lille Nord de France. Institut Pasteur de Lille. Lille, FranceBackground: The chemotherapy of schistosomiasis currently depends on the use of a single drug, praziquantel. In order to develop novel chemotherapeutic agents we are investigating enzymes involved in the epigenetic modification of chromatin. Sirtuins are dependent lysine deacetylases that are involved in a wide variety of cellular processes including histone deacetylation, and have been demonstrated to be therapeutic targets in various pathologies, including cancer. Methodology, Principal Findings: In order to determine whether Schistosoma mansoni sirtuins are potential therapeutic targets we first identified and characterized their protein sequences. Five sirtuins (SmSirt) are encoded in the S. mansoni genome and phylogenetic analysis showed that they are orthologues of mammalian Sirt1, Sirt2, Sirt5, Sirt6 and Sirt7. Both SmSirt1 and SmSirt7 have large insertion in the catalytic domain compared to their mammalian orthologues. SmSirt5 is the only mitochondrial sirtuin encoded in the parasite genome (orthologues of Sirt3 and Sirt4 are absent) and transcripts corresponding to at least five splicing isoforms were identified. All five sirtuins are expressed throughout the parasite life-cycle, but with distinct patterns of expression. Sirtuin inhibitors were used to treat both schistosomula and adult worms maintained in culture. Three inhibitors in particular, Sirtinol, Salermide and MS3 induced apoptosis and death of schistosomula, the separation of adult worm pairs, and a reduction in egg laying. Moreover, Salermide treatment led to a marked disruption of the morphology of ovaries and testes. Transcriptional knockdown of SmSirt1 by RNA interference in adult worms led to morphological changes in the ovaries characterized by a marked increase in mature oocytes, reiterating the effects of sirtuin inhibitors and suggesting that SmSirt1 is their principal target. Conclusion, Significance: Our data demonstrate the potential of schistosome sirtuins as therapeutic targets and validate screening for selective sirtuin inhibitors as a strategy for developing new drugs against schistosomiasisinfo: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/29916/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALSchistosoma mansoni Sirtuins.pdfSchistosoma mansoni Sirtuins.pdfapplication/pdf9468646https://www.arca.fiocruz.br/bitstream/icict/29916/2/Schistosoma%20mansoni%20Sirtuins.pdfa30207edd683e4a22a178acff32f9666MD52TEXTSchistosoma mansoni Sirtuins.pdf.txtSchistosoma mansoni Sirtuins.pdf.txtExtracted texttext/plain97https://www.arca.fiocruz.br/bitstream/icict/29916/3/Schistosoma%20mansoni%20Sirtuins.pdf.txta09249b5294a2f8a123bc4660aec3130MD53icict/299162022-02-01 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dc.title.pt_BR.fl_str_mv Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
title Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
spellingShingle Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
Lancelot, Julien
Esquistossomose
drogas
schistosomiasis
drugs
title_short Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
title_full Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
title_fullStr Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
title_full_unstemmed Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
title_sort Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
author Lancelot, Julien
author_facet Lancelot, Julien
Caby, Stephanie
Dubois-Abdesselem, Florence
Vanderstraete, Mathieu
Trolet, Jacques
Oliveira, Guilherme Corrêa de
Bracher, Franz
Jung, Manfred
Pierce, Raymond John
author_role author
author2 Caby, Stephanie
Dubois-Abdesselem, Florence
Vanderstraete, Mathieu
Trolet, Jacques
Oliveira, Guilherme Corrêa de
Bracher, Franz
Jung, Manfred
Pierce, Raymond John
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Lancelot, Julien
Caby, Stephanie
Dubois-Abdesselem, Florence
Vanderstraete, Mathieu
Trolet, Jacques
Oliveira, Guilherme Corrêa de
Bracher, Franz
Jung, Manfred
Pierce, Raymond John
dc.subject.other.pt_BR.fl_str_mv Esquistossomose
drogas
topic Esquistossomose
drogas
schistosomiasis
drugs
dc.subject.en.pt_BR.fl_str_mv schistosomiasis
drugs
description Center for Infection and Immunity of Lille. Universite Lille Nord de France. Institut Pasteur de Lille. Lille, France
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2018-11-07T12:36:09Z
dc.date.available.fl_str_mv 2018-11-07T12:36:09Z
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 LANCELOT, Julien et al. Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets. PLoS Negl Trop Dis., v. 7, n. 9, e2428, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/29916
dc.identifier.issn.pt_BR.fl_str_mv 1935-2727
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0002428
identifier_str_mv LANCELOT, Julien et al. Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets. PLoS Negl Trop Dis., v. 7, n. 9, e2428, 2013.
1935-2727
10.1371/journal.pntd.0002428
url https://www.arca.fiocruz.br/handle/icict/29916
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 Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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/29916/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/29916/2/Schistosoma%20mansoni%20Sirtuins.pdf
https://www.arca.fiocruz.br/bitstream/icict/29916/3/Schistosoma%20mansoni%20Sirtuins.pdf.txt
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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