Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A

Autores
Bustos, Patricia Laura; Perrone, Alina Elizabeth; Milduberger, Natalia Ayelen; Postan, Miriam; Bua, Jacqueline Elena
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cyclosporin A (CsA) specifically inhibits the mitochondrial permeability transition pore (mPTP). Opening of the mPTP, which is triggered by high levels of matrix [Ca2+] and/or oxidative stress, leads to mitochondrial dysfunction and thus to cell death by either apoptosis or necrosis. In the present study, we analysed the response of Trypanosoma cruzi epimastigote parasites to oxidative stress with 5 mM H2O2, by studying several features related to programmed cell death and the effects of pre-incubation with 1 μM of CsA. We evaluated TcPARP cleavage, DNA integrity, cytochrome c translocation, Annexin V/propidium iodide staining, reactive oxygen species production. CsA prevented parasite oxidative stress damage as it significantly inhibited DNA degradation, cytochrome c translocation to cytosol and TcPARP cleavage. The calcein-AM/ CoCl2 assay, used as a selective indicator of mPTP opening in mammals, was also performed in T. cruzi parasites. H2O2 treatment decreased calcein fluorescence, but this decline was partially inhibited by pre-incubation with CsA. Our results encourage further studies to investigate if there is a mPTP-like pore and a mitochondrial cyclophilin involved in this protozoan parasite.
Fil: Bustos, Patricia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Perrone, Alina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Milduberger, Natalia Ayelen. Universidad Abierta Interamericana; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Postan, Miriam. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Bua, Jacqueline Elena. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Materia
CYCLOPHILIN
CYCLOSPORIN A
OXIDATIVE STRESS
PROGRAMMED CELL DEATH
TRYPANOSOMA CRUZI
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38173
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/38173
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin ABustos, Patricia LauraPerrone, Alina ElizabethMilduberger, Natalia AyelenPostan, MiriamBua, Jacqueline ElenaCYCLOPHILINCYCLOSPORIN AOXIDATIVE STRESSPROGRAMMED CELL DEATHTRYPANOSOMA CRUZIhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cyclosporin A (CsA) specifically inhibits the mitochondrial permeability transition pore (mPTP). Opening of the mPTP, which is triggered by high levels of matrix [Ca2+] and/or oxidative stress, leads to mitochondrial dysfunction and thus to cell death by either apoptosis or necrosis. In the present study, we analysed the response of Trypanosoma cruzi epimastigote parasites to oxidative stress with 5 mM H2O2, by studying several features related to programmed cell death and the effects of pre-incubation with 1 μM of CsA. We evaluated TcPARP cleavage, DNA integrity, cytochrome c translocation, Annexin V/propidium iodide staining, reactive oxygen species production. CsA prevented parasite oxidative stress damage as it significantly inhibited DNA degradation, cytochrome c translocation to cytosol and TcPARP cleavage. The calcein-AM/ CoCl2 assay, used as a selective indicator of mPTP opening in mammals, was also performed in T. cruzi parasites. H2O2 treatment decreased calcein fluorescence, but this decline was partially inhibited by pre-incubation with CsA. Our results encourage further studies to investigate if there is a mPTP-like pore and a mitochondrial cyclophilin involved in this protozoan parasite.Fil: Bustos, Patricia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Perrone, Alina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Milduberger, Natalia Ayelen. Universidad Abierta Interamericana; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Postan, Miriam. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Bua, Jacqueline Elena. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaCambridge University Press2015-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38173Bustos, Patricia Laura; Perrone, Alina Elizabeth; Milduberger, Natalia Ayelen; Postan, Miriam; Bua, Jacqueline Elena; Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A; Cambridge University Press; Parasitology; 142; 8; 7-2015; 1024-10320031-1820CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1017/S0031182015000232info:eu-repo/semantics/altIdentifier/url/https://www.cambridge.org/core/journals/parasitology/article/oxidative-stress-damage-in-the-protozoan-parasite-trypanosoma-cruzi-is-inhibited-by-cyclosporin-a/8658985A3CBDD72F637749304ACD2B55info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:03Zoai:ri.conicet.gov.ar:11336/38173instacron: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:34982025-09-03 10:08:04.159CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A
title Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A
spellingShingle Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A
Bustos, Patricia Laura
CYCLOPHILIN
CYCLOSPORIN A
OXIDATIVE STRESS
PROGRAMMED CELL DEATH
TRYPANOSOMA CRUZI
title_short Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A
title_full Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A
title_fullStr Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A
title_full_unstemmed Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A
title_sort Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A
dc.creator.none.fl_str_mv Bustos, Patricia Laura
Perrone, Alina Elizabeth
Milduberger, Natalia Ayelen
Postan, Miriam
Bua, Jacqueline Elena
author Bustos, Patricia Laura
author_facet Bustos, Patricia Laura
Perrone, Alina Elizabeth
Milduberger, Natalia Ayelen
Postan, Miriam
Bua, Jacqueline Elena
author_role author
author2 Perrone, Alina Elizabeth
Milduberger, Natalia Ayelen
Postan, Miriam
Bua, Jacqueline Elena
author2_role author
author
author
author
dc.subject.none.fl_str_mv CYCLOPHILIN
CYCLOSPORIN A
OXIDATIVE STRESS
PROGRAMMED CELL DEATH
TRYPANOSOMA CRUZI
topic CYCLOPHILIN
CYCLOSPORIN A
OXIDATIVE STRESS
PROGRAMMED CELL DEATH
TRYPANOSOMA CRUZI
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cyclosporin A (CsA) specifically inhibits the mitochondrial permeability transition pore (mPTP). Opening of the mPTP, which is triggered by high levels of matrix [Ca2+] and/or oxidative stress, leads to mitochondrial dysfunction and thus to cell death by either apoptosis or necrosis. In the present study, we analysed the response of Trypanosoma cruzi epimastigote parasites to oxidative stress with 5 mM H2O2, by studying several features related to programmed cell death and the effects of pre-incubation with 1 μM of CsA. We evaluated TcPARP cleavage, DNA integrity, cytochrome c translocation, Annexin V/propidium iodide staining, reactive oxygen species production. CsA prevented parasite oxidative stress damage as it significantly inhibited DNA degradation, cytochrome c translocation to cytosol and TcPARP cleavage. The calcein-AM/ CoCl2 assay, used as a selective indicator of mPTP opening in mammals, was also performed in T. cruzi parasites. H2O2 treatment decreased calcein fluorescence, but this decline was partially inhibited by pre-incubation with CsA. Our results encourage further studies to investigate if there is a mPTP-like pore and a mitochondrial cyclophilin involved in this protozoan parasite.
Fil: Bustos, Patricia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Perrone, Alina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Milduberger, Natalia Ayelen. Universidad Abierta Interamericana; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Postan, Miriam. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Bua, Jacqueline Elena. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
description Cyclosporin A (CsA) specifically inhibits the mitochondrial permeability transition pore (mPTP). Opening of the mPTP, which is triggered by high levels of matrix [Ca2+] and/or oxidative stress, leads to mitochondrial dysfunction and thus to cell death by either apoptosis or necrosis. In the present study, we analysed the response of Trypanosoma cruzi epimastigote parasites to oxidative stress with 5 mM H2O2, by studying several features related to programmed cell death and the effects of pre-incubation with 1 μM of CsA. We evaluated TcPARP cleavage, DNA integrity, cytochrome c translocation, Annexin V/propidium iodide staining, reactive oxygen species production. CsA prevented parasite oxidative stress damage as it significantly inhibited DNA degradation, cytochrome c translocation to cytosol and TcPARP cleavage. The calcein-AM/ CoCl2 assay, used as a selective indicator of mPTP opening in mammals, was also performed in T. cruzi parasites. H2O2 treatment decreased calcein fluorescence, but this decline was partially inhibited by pre-incubation with CsA. Our results encourage further studies to investigate if there is a mPTP-like pore and a mitochondrial cyclophilin involved in this protozoan parasite.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
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/11336/38173
Bustos, Patricia Laura; Perrone, Alina Elizabeth; Milduberger, Natalia Ayelen; Postan, Miriam; Bua, Jacqueline Elena; Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A; Cambridge University Press; Parasitology; 142; 8; 7-2015; 1024-1032
0031-1820
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38173
identifier_str_mv Bustos, Patricia Laura; Perrone, Alina Elizabeth; Milduberger, Natalia Ayelen; Postan, Miriam; Bua, Jacqueline Elena; Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A; Cambridge University Press; Parasitology; 142; 8; 7-2015; 1024-1032
0031-1820
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1017/S0031182015000232
info:eu-repo/semantics/altIdentifier/url/https://www.cambridge.org/core/journals/parasitology/article/oxidative-stress-damage-in-the-protozoan-parasite-trypanosoma-cruzi-is-inhibited-by-cyclosporin-a/8658985A3CBDD72F637749304ACD2B55
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cambridge University Press
publisher.none.fl_str_mv Cambridge University Press
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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