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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/58264
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:06:59Zoai: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:34982025-09-29 10:06:59.566CONICET 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 |
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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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1844613924656250880 |
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13.070432 |