Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)

Detalhes bibliográficos
Autor(a) principal: Sandes, Jana M.
Data de Publicação: 2014
Outros Autores: Fontes, Adriana, Regis-da-Silva, Carlos G., Castro, Maria C. A. Brelaz de, Lima-Junior, Claudio G., Silva, Fábio P. L., Vasconcellos, Mário L. A. A., Figueiredo, Regina C. B. Q.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/23357
Resumo: Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Microbiologia. Recife, PE, Brasil.
id CRUZ_05e1abf8ff2d0908c26187634e9c2eee
oai_identifier_str oai:www.arca.fiocruz.br:icict/23357
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Sandes, Jana M.Fontes, AdrianaRegis-da-Silva, Carlos G.Castro, Maria C. A. Brelaz deLima-Junior, Claudio G.Silva, Fábio P. L.Vasconcellos, Mário L. A. A.Figueiredo, Regina C. B. Q.2017-11-27T11:57:20Z2017-11-27T11:57:20Z2014SANDES, J. M. et al. Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile). PloS One, v. 9, n. 4, p. e93936, 2014.1932-6203https://www.arca.fiocruz.br/handle/icict/2335710.1371/journal.pone.0093936engPublic Library of ScienceTrypanosoma cruziDoença de ChagasTrypanosoma cruziChagas DiseaseAcrilonitrilaanálogos & derivadosÁlcoois BenzílicosfarmacologiaMorte Celularefeitos de drogasDoença de Chagastratamento farmacológicoTrypanosoma cruzicitoplasmaMembrana CelularparasitologiaMicroscopia ConfocalPotencial da Membrana MitocondriaTrypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Microbiologia. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Biofísica e Radiobiologia. Recife, PE, Brazil.Fundação Oswaldo Cruz. Centro Pesquisas Gonçalo Moniz. Laboratório de Biologia Parasitaria. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Recife, PE, Brasil.Universidade Federal da Paraíba. Departamento de Química. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Departamento de Química. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Departamento de Química. João Pessoa, PB, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Microbiologia. Recife, PE, Brasil.Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a serious health concern due to the lack of effective vaccines or satisfactory treatment. In the search for new compounds against this neglected disease, we have previously demonstrated that the compound 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile) (MBHA3), derived from the Morita-Baylis-Hillman reaction, effectively caused a loss of viability in both the epimastigote and trypomastigote forms. However, the mechanisms of parasite death elicited by MBHA3 remain unknown. The aim of this study was to better understand the morphophysiological changes and the mechanism of cell death induced by MBHA3 treatment on T. cruzi. To perform this analysis, we used confocal microscopy and flow cytometry to monitor the fluorescent probes such as annexin-V/propidium iodide (AV/PI), calcein-AM/ethidium homodimer (CA/EH), acridine orange (AO) and rhodamine 123 (Rho 123). Lower concentrations of MBHA3 led to alterations in the mitochondrial membrane potential and AO labeling, but did not decrease the viability of the epimastiogote forms, as determined by the CA/EH and AV/PI assays. Conversely, treatment with higher concentrations of MBHA3 led to extensive plasma membrane damage, loss of mitochondrion membrane potential, DNA fragmentation and acidification of the cytoplasm. Our findings suggest that at higher concentrations, MBHA3 induces T. cruzi epimastigote death by necrosis in a mitochondrion-dependent manner.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83092https://www.arca.fiocruz.br/bitstream/icict/23357/1/license.txt447f2497af1ef5cf99b5c07f6fa18dceMD51ORIGINALart. Trypanosoma cruzi - sandes.pdfart. Trypanosoma cruzi - sandes.pdfapplication/pdf5943676https://www.arca.fiocruz.br/bitstream/icict/23357/2/art.%20Trypanosoma%20cruzi%20-%20sandes.pdfc33130d68adc83b9c57c45ec2b59ed34MD52TEXTart. Trypanosoma cruzi - sandes.pdf.txtart. Trypanosoma cruzi - sandes.pdf.txtExtracted texttext/plain40305https://www.arca.fiocruz.br/bitstream/icict/23357/3/art.%20Trypanosoma%20cruzi%20-%20sandes.pdf.txtd82290936f594ef1f3ebe78491b14074MD53icict/233572018-12-21 09:29:18.648oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352018-12-21T11:29:18Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)
title Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)
spellingShingle Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)
Sandes, Jana M.
Trypanosoma cruzi
Doença de Chagas
Trypanosoma cruzi
Chagas Disease
Acrilonitrila
análogos & derivados
Álcoois Benzílicos
farmacologia
Morte Celular
efeitos de drogas
Doença de Chagas
tratamento farmacológico
Trypanosoma cruzi
citoplasma
Membrana Celular
parasitologia
Microscopia Confocal
Potencial da Membrana Mitocondria
title_short Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)
title_full Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)
title_fullStr Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)
title_full_unstemmed Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)
title_sort Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile)
author Sandes, Jana M.
author_facet Sandes, Jana M.
Fontes, Adriana
Regis-da-Silva, Carlos G.
Castro, Maria C. A. Brelaz de
Lima-Junior, Claudio G.
Silva, Fábio P. L.
Vasconcellos, Mário L. A. A.
Figueiredo, Regina C. B. Q.
author_role author
author2 Fontes, Adriana
Regis-da-Silva, Carlos G.
Castro, Maria C. A. Brelaz de
Lima-Junior, Claudio G.
Silva, Fábio P. L.
Vasconcellos, Mário L. A. A.
Figueiredo, Regina C. B. Q.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Sandes, Jana M.
Fontes, Adriana
Regis-da-Silva, Carlos G.
Castro, Maria C. A. Brelaz de
Lima-Junior, Claudio G.
Silva, Fábio P. L.
Vasconcellos, Mário L. A. A.
Figueiredo, Regina C. B. Q.
dc.subject.other.pt_BR.fl_str_mv Trypanosoma cruzi
Doença de Chagas
topic Trypanosoma cruzi
Doença de Chagas
Trypanosoma cruzi
Chagas Disease
Acrilonitrila
análogos & derivados
Álcoois Benzílicos
farmacologia
Morte Celular
efeitos de drogas
Doença de Chagas
tratamento farmacológico
Trypanosoma cruzi
citoplasma
Membrana Celular
parasitologia
Microscopia Confocal
Potencial da Membrana Mitocondria
dc.subject.en.pt_BR.fl_str_mv Trypanosoma cruzi
Chagas Disease
dc.subject.decs.pt_BR.fl_str_mv Acrilonitrila
análogos & derivados
Álcoois Benzílicos
farmacologia
Morte Celular
efeitos de drogas
Doença de Chagas
tratamento farmacológico
Trypanosoma cruzi
citoplasma
Membrana Celular
parasitologia
Microscopia Confocal
Potencial da Membrana Mitocondria
description Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Microbiologia. Recife, PE, Brasil.
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2017-11-27T11:57:20Z
dc.date.available.fl_str_mv 2017-11-27T11:57:20Z
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 SANDES, J. M. et al. Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile). PloS One, v. 9, n. 4, p. e93936, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/23357
dc.identifier.issn.pt_BR.fl_str_mv 1932-6203
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pone.0093936
identifier_str_mv SANDES, J. M. et al. Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile). PloS One, v. 9, n. 4, p. e93936, 2014.
1932-6203
10.1371/journal.pone.0093936
url https://www.arca.fiocruz.br/handle/icict/23357
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/23357/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/23357/2/art.%20Trypanosoma%20cruzi%20-%20sandes.pdf
https://www.arca.fiocruz.br/bitstream/icict/23357/3/art.%20Trypanosoma%20cruzi%20-%20sandes.pdf.txt
bitstream.checksum.fl_str_mv 447f2497af1ef5cf99b5c07f6fa18dce
c33130d68adc83b9c57c45ec2b59ed34
d82290936f594ef1f3ebe78491b14074
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1813009018856144896