Clomipramine kills Trypanosoma brucei by apoptosis

Autores
de Silva Rodrigues, Jean Hernrique; Stein, Jasmin; Strauss, Mariana; Rivarola, Hector Walter; Ueda Nakamura, Tania; Nakamura, Celso Vaturu; Duszenko, Michael
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Drug repositioning, i.e. use of existing medicals to treat a different illness, is especially rewarding for neglected tropical diseases (NTD), since in this field the pharmaceutical industry is rather reluctant to spend vast investments for drug development. NTDs afflict primarily poor populations in under-developed countries, which minimizes financial profit. Here we investigated the trypanocidal effect of clomipramine, a commercial antipsychotic drug, on Trypanosoma brucei. The data showed that this drug killed the parasite with an IC50 of about 5 μM. Analysis of the involved cell death mechanism revealed furthermore an initial autophagic stress response and finally the induction of apoptosis. The latter was substantiated by a set of respective markers such as phosphatidylserine exposition, DNA degradation, loss of the inner mitochondrial membrane potential and characteristic morphological changes. Clomipramine was described as a trypanothione inhibitor, but as judged from our results it also showed DNA binding capacities and induced substantial morphological changes. We thus consider it likely that the drug induces a multifold adverse interaction with the parasite?s physiology and induces stress in a way that trypanosomes cannot cope with.
Fil: de Silva Rodrigues, Jean Hernrique. Universidade Estadual de Maringá; Brasil. University of Tübingen. Interfaculty Institute of Biochemistry; Alemania
Fil: Stein, Jasmin. University Of Tübingen, Interfaculty Institute Of Bioch; Alemania
Fil: Strauss, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Rivarola, Hector Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Ueda Nakamura, Tania. Universidade Estadual de Maringa; Brasil
Fil: Nakamura, Celso Vaturu. Universidade Estadual de Maringa; Brasil
Fil: Duszenko, Michael. University Of Tübingen, Interfaculty Institute Of Bioch; Alemania
Materia
Apoptosis
Clomipramine
Sleeping Sickness
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/58264
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/58264
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Clomipramine kills Trypanosoma brucei by apoptosisde Silva Rodrigues, Jean HernriqueStein, JasminStrauss, MarianaRivarola, Hector WalterUeda Nakamura, TaniaNakamura, Celso VaturuDuszenko, MichaelApoptosisClomipramineSleeping Sicknesshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Drug repositioning, i.e. use of existing medicals to treat a different illness, is especially rewarding for neglected tropical diseases (NTD), since in this field the pharmaceutical industry is rather reluctant to spend vast investments for drug development. NTDs afflict primarily poor populations in under-developed countries, which minimizes financial profit. Here we investigated the trypanocidal effect of clomipramine, a commercial antipsychotic drug, on Trypanosoma brucei. The data showed that this drug killed the parasite with an IC50 of about 5 μM. Analysis of the involved cell death mechanism revealed furthermore an initial autophagic stress response and finally the induction of apoptosis. The latter was substantiated by a set of respective markers such as phosphatidylserine exposition, DNA degradation, loss of the inner mitochondrial membrane potential and characteristic morphological changes. Clomipramine was described as a trypanothione inhibitor, but as judged from our results it also showed DNA binding capacities and induced substantial morphological changes. We thus consider it likely that the drug induces a multifold adverse interaction with the parasite?s physiology and induces stress in a way that trypanosomes cannot cope with.Fil: de Silva Rodrigues, Jean Hernrique. Universidade Estadual de Maringá; Brasil. University of Tübingen. Interfaculty Institute of Biochemistry; AlemaniaFil: Stein, Jasmin. University Of Tübingen, Interfaculty Institute Of Bioch; AlemaniaFil: Strauss, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Rivarola, Hector Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Ueda Nakamura, Tania. Universidade Estadual de Maringa; BrasilFil: Nakamura, Celso Vaturu. Universidade Estadual de Maringa; BrasilFil: Duszenko, Michael. University Of Tübingen, Interfaculty Institute Of Bioch; AlemaniaElsevier Gmbh2016-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/58264de Silva Rodrigues, Jean Hernrique; Stein, Jasmin; Strauss, Mariana; Rivarola, Hector Walter; Ueda Nakamura, Tania; et al.; Clomipramine kills Trypanosoma brucei by apoptosis; Elsevier Gmbh; International Journal of Medical Microbiology (print); 16; 4; 4-2016; 1438-42211438-4221CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijmm.2016.03.009info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1438422116300297info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:03:54Zoai:ri.conicet.gov.ar:11336/58264instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:03:54.797CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Clomipramine kills Trypanosoma brucei by apoptosis
title Clomipramine kills Trypanosoma brucei by apoptosis
spellingShingle Clomipramine kills Trypanosoma brucei by apoptosis
de Silva Rodrigues, Jean Hernrique
Apoptosis
Clomipramine
Sleeping Sickness
title_short Clomipramine kills Trypanosoma brucei by apoptosis
title_full Clomipramine kills Trypanosoma brucei by apoptosis
title_fullStr Clomipramine kills Trypanosoma brucei by apoptosis
title_full_unstemmed Clomipramine kills Trypanosoma brucei by apoptosis
title_sort Clomipramine kills Trypanosoma brucei by apoptosis
dc.creator.none.fl_str_mv de Silva Rodrigues, Jean Hernrique
Stein, Jasmin
Strauss, Mariana
Rivarola, Hector Walter
Ueda Nakamura, Tania
Nakamura, Celso Vaturu
Duszenko, Michael
author de Silva Rodrigues, Jean Hernrique
author_facet de Silva Rodrigues, Jean Hernrique
Stein, Jasmin
Strauss, Mariana
Rivarola, Hector Walter
Ueda Nakamura, Tania
Nakamura, Celso Vaturu
Duszenko, Michael
author_role author
author2 Stein, Jasmin
Strauss, Mariana
Rivarola, Hector Walter
Ueda Nakamura, Tania
Nakamura, Celso Vaturu
Duszenko, Michael
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Clomipramine
Sleeping Sickness
topic Apoptosis
Clomipramine
Sleeping Sickness
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Drug repositioning, i.e. use of existing medicals to treat a different illness, is especially rewarding for neglected tropical diseases (NTD), since in this field the pharmaceutical industry is rather reluctant to spend vast investments for drug development. NTDs afflict primarily poor populations in under-developed countries, which minimizes financial profit. Here we investigated the trypanocidal effect of clomipramine, a commercial antipsychotic drug, on Trypanosoma brucei. The data showed that this drug killed the parasite with an IC50 of about 5 μM. Analysis of the involved cell death mechanism revealed furthermore an initial autophagic stress response and finally the induction of apoptosis. The latter was substantiated by a set of respective markers such as phosphatidylserine exposition, DNA degradation, loss of the inner mitochondrial membrane potential and characteristic morphological changes. Clomipramine was described as a trypanothione inhibitor, but as judged from our results it also showed DNA binding capacities and induced substantial morphological changes. We thus consider it likely that the drug induces a multifold adverse interaction with the parasite?s physiology and induces stress in a way that trypanosomes cannot cope with.
Fil: de Silva Rodrigues, Jean Hernrique. Universidade Estadual de Maringá; Brasil. University of Tübingen. Interfaculty Institute of Biochemistry; Alemania
Fil: Stein, Jasmin. University Of Tübingen, Interfaculty Institute Of Bioch; Alemania
Fil: Strauss, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Rivarola, Hector Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Ueda Nakamura, Tania. Universidade Estadual de Maringa; Brasil
Fil: Nakamura, Celso Vaturu. Universidade Estadual de Maringa; Brasil
Fil: Duszenko, Michael. University Of Tübingen, Interfaculty Institute Of Bioch; Alemania
description Drug repositioning, i.e. use of existing medicals to treat a different illness, is especially rewarding for neglected tropical diseases (NTD), since in this field the pharmaceutical industry is rather reluctant to spend vast investments for drug development. NTDs afflict primarily poor populations in under-developed countries, which minimizes financial profit. Here we investigated the trypanocidal effect of clomipramine, a commercial antipsychotic drug, on Trypanosoma brucei. The data showed that this drug killed the parasite with an IC50 of about 5 μM. Analysis of the involved cell death mechanism revealed furthermore an initial autophagic stress response and finally the induction of apoptosis. The latter was substantiated by a set of respective markers such as phosphatidylserine exposition, DNA degradation, loss of the inner mitochondrial membrane potential and characteristic morphological changes. Clomipramine was described as a trypanothione inhibitor, but as judged from our results it also showed DNA binding capacities and induced substantial morphological changes. We thus consider it likely that the drug induces a multifold adverse interaction with the parasite?s physiology and induces stress in a way that trypanosomes cannot cope with.
publishDate 2016
dc.date.none.fl_str_mv 2016-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/58264
de Silva Rodrigues, Jean Hernrique; Stein, Jasmin; Strauss, Mariana; Rivarola, Hector Walter; Ueda Nakamura, Tania; et al.; Clomipramine kills Trypanosoma brucei by apoptosis; Elsevier Gmbh; International Journal of Medical Microbiology (print); 16; 4; 4-2016; 1438-4221
1438-4221
CONICET Digital
CONICET
url http://hdl.handle.net/11336/58264
identifier_str_mv de Silva Rodrigues, Jean Hernrique; Stein, Jasmin; Strauss, Mariana; Rivarola, Hector Walter; Ueda Nakamura, Tania; et al.; Clomipramine kills Trypanosoma brucei by apoptosis; Elsevier Gmbh; International Journal of Medical Microbiology (print); 16; 4; 4-2016; 1438-4221
1438-4221
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijmm.2016.03.009
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1438422116300297
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Gmbh
publisher.none.fl_str_mv Elsevier Gmbh
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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