CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells

Autores
Kamida, Javier; Dib, Camila; Santa Coloma, Tomás Antonio; Valdivieso, Ángel Gabriel
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The impairment of the CFTR channel, a cAMP-activated chloride(Cl-) channel responsible for cystic fibrosis (CF), has been associated with a variety of mitochondrial alterations. Recently, we reportedan increase in mitochondrial fragmentation induced by the inhibitionof the CFTR activity. The cAMP treatment to stimulate the CFTRactivity worsen this phenotype in CF cells. Here, we analysed themitochondrial network in CF cells treated with the CFTR modulatorsLumacaftor (VX-809)/Ivacaftor (VX-770) VX-809 act as pharmacological chaperone, increasing the amount of CFTR at the cell membrane surface; while VX-770 increase the activation of the CFTR.Single, combined and sequential treatments with VX-809 (10 μM,CFTR corrector) and VX-770 (10, 1 and 0.1 μM, CFTR enhancer)were performed in IB3-1 cells (CF cells). Also, cAMP was tested asa CFTR stimulator to compare its effect with VX-770. Mitochondriawere labelled with MitoTracker Orange, imaged by confocal microscopy, and analysed with Mitochondrial Network Analysis (MiNA)plugin for Fiji. A single treatment with VX-80948 h, but not with VX770, reduced the mitochondrial fragmentation in IB3-1 cells, whilea combined treatment with VX-809/ VX-770 for 48 h had no effect.However, the preincubation with VX-809 24 h previous to VX-770 foranother 24 h reduced significantly the mitochondrial fragmentation.Similar results were observed using cAMP to stimulate the CFTRactivity. These results suggest that CFTR potentiators could impairthe mitochondrial dynamics when the CFTR is not expressed onthe membrane surface. Further research is needed to identify themechanisms involved in this regulation to improve the therapy byusing these drugs.
Fil: Kamida, Javier. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Dib, Camila. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Reunión Anual de las Sociedades de Biociencia: LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Immunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
Materia
IVACAFTOR
LUMACAFTOR
CFTR
MITOCHONDRIA
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:11336/269386
Acceder
id CONICETDig_8c992cb07535a2ab9ea9f553d94eb90a
oai_identifier_str oai:ri.conicet.gov.ar:11336/269386
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cellsKamida, JavierDib, CamilaSanta Coloma, Tomás AntonioValdivieso, Ángel GabrielIVACAFTORLUMACAFTORCFTRMITOCHONDRIAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The impairment of the CFTR channel, a cAMP-activated chloride(Cl-) channel responsible for cystic fibrosis (CF), has been associated with a variety of mitochondrial alterations. Recently, we reportedan increase in mitochondrial fragmentation induced by the inhibitionof the CFTR activity. The cAMP treatment to stimulate the CFTRactivity worsen this phenotype in CF cells. Here, we analysed themitochondrial network in CF cells treated with the CFTR modulatorsLumacaftor (VX-809)/Ivacaftor (VX-770) VX-809 act as pharmacological chaperone, increasing the amount of CFTR at the cell membrane surface; while VX-770 increase the activation of the CFTR.Single, combined and sequential treatments with VX-809 (10 μM,CFTR corrector) and VX-770 (10, 1 and 0.1 μM, CFTR enhancer)were performed in IB3-1 cells (CF cells). Also, cAMP was tested asa CFTR stimulator to compare its effect with VX-770. Mitochondriawere labelled with MitoTracker Orange, imaged by confocal microscopy, and analysed with Mitochondrial Network Analysis (MiNA)plugin for Fiji. A single treatment with VX-80948 h, but not with VX770, reduced the mitochondrial fragmentation in IB3-1 cells, whilea combined treatment with VX-809/ VX-770 for 48 h had no effect.However, the preincubation with VX-809 24 h previous to VX-770 foranother 24 h reduced significantly the mitochondrial fragmentation.Similar results were observed using cAMP to stimulate the CFTRactivity. These results suggest that CFTR potentiators could impairthe mitochondrial dynamics when the CFTR is not expressed onthe membrane surface. Further research is needed to identify themechanisms involved in this regulation to improve the therapy byusing these drugs.Fil: Kamida, Javier. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Dib, Camila. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaReunión Anual de las Sociedades de Biociencia: LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Immunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de NanomedicinasArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de NanomedicinasFundación Revista Medicina2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/269386CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells; Reunión Anual de las Sociedades de Biociencia: LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Immunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 249-2491669-9106CONICET DigitalCONICETengNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:27:06Zoai:ri.conicet.gov.ar:11336/269386instacron: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 10:27:06.515CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells
title CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells
spellingShingle CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells
Kamida, Javier
IVACAFTOR
LUMACAFTOR
CFTR
MITOCHONDRIA
title_short CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells
title_full CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells
title_fullStr CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells
title_full_unstemmed CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells
title_sort CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells
dc.creator.none.fl_str_mv Kamida, Javier
Dib, Camila
Santa Coloma, Tomás Antonio
Valdivieso, Ángel Gabriel
author Kamida, Javier
author_facet Kamida, Javier
Dib, Camila
Santa Coloma, Tomás Antonio
Valdivieso, Ángel Gabriel
author_role author
author2 Dib, Camila
Santa Coloma, Tomás Antonio
Valdivieso, Ángel Gabriel
author2_role author
author
author
dc.subject.none.fl_str_mv IVACAFTOR
LUMACAFTOR
CFTR
MITOCHONDRIA
topic IVACAFTOR
LUMACAFTOR
CFTR
MITOCHONDRIA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The impairment of the CFTR channel, a cAMP-activated chloride(Cl-) channel responsible for cystic fibrosis (CF), has been associated with a variety of mitochondrial alterations. Recently, we reportedan increase in mitochondrial fragmentation induced by the inhibitionof the CFTR activity. The cAMP treatment to stimulate the CFTRactivity worsen this phenotype in CF cells. Here, we analysed themitochondrial network in CF cells treated with the CFTR modulatorsLumacaftor (VX-809)/Ivacaftor (VX-770) VX-809 act as pharmacological chaperone, increasing the amount of CFTR at the cell membrane surface; while VX-770 increase the activation of the CFTR.Single, combined and sequential treatments with VX-809 (10 μM,CFTR corrector) and VX-770 (10, 1 and 0.1 μM, CFTR enhancer)were performed in IB3-1 cells (CF cells). Also, cAMP was tested asa CFTR stimulator to compare its effect with VX-770. Mitochondriawere labelled with MitoTracker Orange, imaged by confocal microscopy, and analysed with Mitochondrial Network Analysis (MiNA)plugin for Fiji. A single treatment with VX-80948 h, but not with VX770, reduced the mitochondrial fragmentation in IB3-1 cells, whilea combined treatment with VX-809/ VX-770 for 48 h had no effect.However, the preincubation with VX-809 24 h previous to VX-770 foranother 24 h reduced significantly the mitochondrial fragmentation.Similar results were observed using cAMP to stimulate the CFTRactivity. These results suggest that CFTR potentiators could impairthe mitochondrial dynamics when the CFTR is not expressed onthe membrane surface. Further research is needed to identify themechanisms involved in this regulation to improve the therapy byusing these drugs.
Fil: Kamida, Javier. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Dib, Camila. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Reunión Anual de las Sociedades de Biociencia: LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Immunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
description The impairment of the CFTR channel, a cAMP-activated chloride(Cl-) channel responsible for cystic fibrosis (CF), has been associated with a variety of mitochondrial alterations. Recently, we reportedan increase in mitochondrial fragmentation induced by the inhibitionof the CFTR activity. The cAMP treatment to stimulate the CFTRactivity worsen this phenotype in CF cells. Here, we analysed themitochondrial network in CF cells treated with the CFTR modulatorsLumacaftor (VX-809)/Ivacaftor (VX-770) VX-809 act as pharmacological chaperone, increasing the amount of CFTR at the cell membrane surface; while VX-770 increase the activation of the CFTR.Single, combined and sequential treatments with VX-809 (10 μM,CFTR corrector) and VX-770 (10, 1 and 0.1 μM, CFTR enhancer)were performed in IB3-1 cells (CF cells). Also, cAMP was tested asa CFTR stimulator to compare its effect with VX-770. Mitochondriawere labelled with MitoTracker Orange, imaged by confocal microscopy, and analysed with Mitochondrial Network Analysis (MiNA)plugin for Fiji. A single treatment with VX-80948 h, but not with VX770, reduced the mitochondrial fragmentation in IB3-1 cells, whilea combined treatment with VX-809/ VX-770 for 48 h had no effect.However, the preincubation with VX-809 24 h previous to VX-770 foranother 24 h reduced significantly the mitochondrial fragmentation.Similar results were observed using cAMP to stimulate the CFTRactivity. These results suggest that CFTR potentiators could impairthe mitochondrial dynamics when the CFTR is not expressed onthe membrane surface. Further research is needed to identify themechanisms involved in this regulation to improve the therapy byusing these drugs.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/269386
CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells; Reunión Anual de las Sociedades de Biociencia: LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Immunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 249-249
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/269386
identifier_str_mv CFTR correction with lumacaftor/ivacaftor reduced the mitochondrial fragmentation in cystic fibrosis cultured epithelial cells; Reunión Anual de las Sociedades de Biociencia: LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Immunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 249-249
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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 13.070432

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