The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes

Detalhes bibliográficos
Autor(a) principal: Marinho, Fernanda A
Data de Publicação: 2014
Outros Autores: Gonçalves, Keyla C. S, Oliveira, Simone S. C, Gonçalves, Diego S, Matteoli, Filipe P, Seabra, Sergio H., Oliveira, Ana Carolina S, Belllo, Maria, Oliveira, Selma S, Padrón, Thaís Souto, Levy, Claudia Masini d'Avila, Santos, André L. S, Branquinha, Marta H
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/10175
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.
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spelling Marinho, Fernanda AGonçalves, Keyla C. SOliveira, Simone S. CGonçalves, Diego SMatteoli, Filipe PSeabra, Sergio H.Oliveira, Ana Carolina SBelllo, MariaOliveira, Selma SPadrón, Thaís SoutoLevy, Claudia Masini d'AvilaSantos, André L. SBranquinha, Marta H2015-05-04T16:34:34Z2015-05-04T16:34:34Z2014MARINHO, Fernanda A. et al. The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes. Plos One, v.9, n.1, 11p, 2014.https://www.arca.fiocruz.br/handle/icict/1017510.1371/journal.pone.0087659engPlos OneThe Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.Centro Universitário Estadual da Zona Oeste (UEZO). Laboratório de Tecnologia em Cultura de Cèlulas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro.Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. IMPG. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Cieˆncia e Tecnologia de Biologia Estrutural e Bioimagem (INBEB). Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.Background Human cutaneous leishmaniasis is caused by distinct species, including Leishmania amazonensis. Treatment of cutaneous leishmaniasis is far from satisfactory due to increases in drug resistance and relapses, and toxicity of compounds to the host. As a consequence for this situation, the development of new leishmanicidal drugs and the search of new targets in the parasite biology are important goals. Methodology/Principal Findings In this study, we investigated the mechanism of death pathway induced by the calpain inhibitor MDL28170 on Leishmania amazonensis promastigote forms. The combined use of different techniques was applied to contemplate this goal. MDL28170 treatment with IC50 (15 µM) and two times the IC50 doses induced loss of parasite viability, as verified by resazurin assay, as well as depolarization of the mitochondrial membrane, which was quantified by JC-1 staining. Scanning and transmission electron microscopic images revealed drastic alterations on the parasite morphology, some of them resembling apoptotic-like death, including cell shrinking, surface membrane blebs and altered chromatin condensation pattern. The lipid rearrangement of the plasma membrane was detected by Annexin-V labeling. The inhibitor also induced a significant increase in the proportion of cells in the sub-G0/G1 phase, as quantified by propidium iodide staining, as well as genomic DNA fragmentation, detected by TUNEL assay. In cells treated with MDL28170 at two times the IC50 dose, it was also possible to observe an oligonucleossomal DNA fragmentation by agarose gel electrophoresis. Conclusions/Significance The data presented in the current study suggest that MDL28170 induces apoptotic marker expression in promastigotes of L. amazonensis. Altogether, the results described in the present work not only provide a rationale for further exploration of the mechanism of action of calpain inhibitors against trypanosomatids, but may also widen the investigation of the potential clinical utility of calpain inhibitors in the chemotherapy of leishmaniases.LeishmaniaCalpain Inhibitor MDL28170Ciências Biológicasinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/10175/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALkeyla_gonçalvesetal_IOC_2014.pdfapplication/pdf1280138https://www.arca.fiocruz.br/bitstream/icict/10175/2/keyla_gon%c3%a7alvesetal_IOC_2014.pdffce894fdf3a60fb0c49b1591c0307201MD52TEXTkeyla_gonçalvesetal_IOC_2014.pdf.txtkeyla_gonçalvesetal_IOC_2014.pdf.txtExtracted texttext/plain59223https://www.arca.fiocruz.br/bitstream/icict/10175/3/keyla_gon%c3%a7alvesetal_IOC_2014.pdf.txte73974e3e6f0879bafc9085843de3c37MD53icict/101752022-06-24 13:04:24.454oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T16:04:24Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
title The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
spellingShingle The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
Marinho, Fernanda A
Leishmania
Calpain Inhibitor MDL28170
Ciências Biológicas
title_short The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
title_full The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
title_fullStr The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
title_full_unstemmed The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
title_sort The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
author Marinho, Fernanda A
author_facet Marinho, Fernanda A
Gonçalves, Keyla C. S
Oliveira, Simone S. C
Gonçalves, Diego S
Matteoli, Filipe P
Seabra, Sergio H.
Oliveira, Ana Carolina S
Belllo, Maria
Oliveira, Selma S
Padrón, Thaís Souto
Levy, Claudia Masini d'Avila
Santos, André L. S
Branquinha, Marta H
author_role author
author2 Gonçalves, Keyla C. S
Oliveira, Simone S. C
Gonçalves, Diego S
Matteoli, Filipe P
Seabra, Sergio H.
Oliveira, Ana Carolina S
Belllo, Maria
Oliveira, Selma S
Padrón, Thaís Souto
Levy, Claudia Masini d'Avila
Santos, André L. S
Branquinha, Marta H
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Marinho, Fernanda A
Gonçalves, Keyla C. S
Oliveira, Simone S. C
Gonçalves, Diego S
Matteoli, Filipe P
Seabra, Sergio H.
Oliveira, Ana Carolina S
Belllo, Maria
Oliveira, Selma S
Padrón, Thaís Souto
Levy, Claudia Masini d'Avila
Santos, André L. S
Branquinha, Marta H
dc.subject.en.pt_BR.fl_str_mv Leishmania
Calpain Inhibitor MDL28170
topic Leishmania
Calpain Inhibitor MDL28170
Ciências Biológicas
dc.subject.decs.pt_BR.fl_str_mv Ciências Biológicas
description Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2015-05-04T16:34:34Z
dc.date.available.fl_str_mv 2015-05-04T16:34:34Z
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 MARINHO, Fernanda A. et al. The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes. Plos One, v.9, n.1, 11p, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/10175
dc.identifier.doi.pt_BR.fl_str_mv 10.1371/journal.pone.0087659
identifier_str_mv MARINHO, Fernanda A. et al. The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes. Plos One, v.9, n.1, 11p, 2014.
10.1371/journal.pone.0087659
url https://www.arca.fiocruz.br/handle/icict/10175
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 Plos One
publisher.none.fl_str_mv Plos One
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)
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