Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion

Autores
Valdivieso, Ángel Gabriel; Clauzure, Mariángeles; Massip Copiz, María Macarena; Cancio, Carla E.; Asensio, Cristian J. A.; Mori, Consuelo; Santa Coloma, Tomás Antonio
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión aceptada
Descripción
Fil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Valdivieso, Ángel Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Clauzure, Mariángeles. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Clauzure, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Massip Copiz, María Macarena. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Massip Copiz, María Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cancio, Carla E. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cancio, Carla E. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Asensio, Cristian. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Asensio, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mori, Consuelo. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Mori, Consuelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Santa Coloma, Tomás Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Asbtract: Mutations in the gene encoding the CFTR chloride channel produce cystic fibrosis (CF). CF patients are more susceptible to bacterial infections in lungs. The most accepted hypothesis sustains that a reduction in the airway surface liquid (ASL) volume favor infections. Alternatively, it was postulated that a reduced HCO3- transport through CFTR leads to a decreased ASL pH, favoring bacterial colonization. The issue is controversial, since recent data from cultured primary cells and CF children showed normal pH values in the ASL. We have reported previously a decreased mitochondrial Complex I (mCx-I) activity in cultured cells with impaired CFTR activity. Thus, we hypothesized that the reduced mCx-I activity could lead to increased lactic acid production (Warburg-like effect) and reduced extracellular pH (pHe). In agreement with this idea, we report here that cells with impaired CFTR function (intestinal Caco-2/pRS26, transfected with an shRNA-CFTR, and lung IB3-1 CF cells) have a decreased pHe. These cells showed increased lactate dehydrogenase (LDH) activity, LDH-A expression, and lactate secretion. Similar effects were reproduced in control cells stimulated with recombinant IL-1β. The c-Src and JNK inhibitors PP2 and SP600125 were able to increase the pHe, although the differences between control and CFTR-impaired cells were not fully compensated. Noteworthy, the LDH inhibitor oxamate completely restored the pHe of the intestinal Caco-2/pRS26 cells and have a significant effect in lung IB3-1 cells; therefore, an increased lactic acid secretion seems to be the key factor that determine a reduced pHe in these epithelial cells.
Fuente
Cellular and Molecular Life Sciences. 2019, 76
Materia
CFTR
FIBROSIS QUISTICA
INFLAMACION
CELULAS EPITELIALES
INTESTINOS
ACIDO LACTICO
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/9596
Acceder
id RIUCA_ce94ae1ec83030a76a4508695ad28824
oai_identifier_str oai:ucacris:123456789/9596
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretionValdivieso, Ángel GabrielClauzure, MariángelesMassip Copiz, María MacarenaCancio, Carla E.Asensio, Cristian J. A.Mori, ConsueloSanta Coloma, Tomás AntonioCFTRFIBROSIS QUISTICAINFLAMACIONCELULAS EPITELIALESINTESTINOSACIDO LACTICOFil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Valdivieso, Ángel Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Clauzure, Mariángeles. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Clauzure, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Massip Copiz, María Macarena. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Massip Copiz, María Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cancio, Carla E. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cancio, Carla E. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Asensio, Cristian. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Asensio, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mori, Consuelo. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Mori, Consuelo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Santa Coloma, Tomás Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAsbtract: Mutations in the gene encoding the CFTR chloride channel produce cystic fibrosis (CF). CF patients are more susceptible to bacterial infections in lungs. The most accepted hypothesis sustains that a reduction in the airway surface liquid (ASL) volume favor infections. Alternatively, it was postulated that a reduced HCO3- transport through CFTR leads to a decreased ASL pH, favoring bacterial colonization. The issue is controversial, since recent data from cultured primary cells and CF children showed normal pH values in the ASL. We have reported previously a decreased mitochondrial Complex I (mCx-I) activity in cultured cells with impaired CFTR activity. Thus, we hypothesized that the reduced mCx-I activity could lead to increased lactic acid production (Warburg-like effect) and reduced extracellular pH (pHe). In agreement with this idea, we report here that cells with impaired CFTR function (intestinal Caco-2/pRS26, transfected with an shRNA-CFTR, and lung IB3-1 CF cells) have a decreased pHe. These cells showed increased lactate dehydrogenase (LDH) activity, LDH-A expression, and lactate secretion. Similar effects were reproduced in control cells stimulated with recombinant IL-1β. The c-Src and JNK inhibitors PP2 and SP600125 were able to increase the pHe, although the differences between control and CFTR-impaired cells were not fully compensated. Noteworthy, the LDH inhibitor oxamate completely restored the pHe of the intestinal Caco-2/pRS26 cells and have a significant effect in lung IB3-1 cells; therefore, an increased lactic acid secretion seems to be the key factor that determine a reduced pHe in these epithelial cells.Springer2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/95961420-9071 (online)1420-682X (impreso)10.1007/s00018-018-3001-y30599064Valdivieso, A.G. et al. Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion [en línea]. Cellular and Molecular Life Sciences. 2019, 76. doi:10.1007/s00018-018-3001-y Disponible en: https://repositorio.uca.edu.ar/handle/123456789/9596Cellular and Molecular Life Sciences. 2019, 76reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:57:11Zoai:ucacris:123456789/9596instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:57:11.629Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
title Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
spellingShingle Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
Valdivieso, Ángel Gabriel
CFTR
FIBROSIS QUISTICA
INFLAMACION
CELULAS EPITELIALES
INTESTINOS
ACIDO LACTICO
title_short Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
title_full Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
title_fullStr Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
title_full_unstemmed Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
title_sort Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
dc.creator.none.fl_str_mv Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Massip Copiz, María Macarena
Cancio, Carla E.
Asensio, Cristian J. A.
Mori, Consuelo
Santa Coloma, Tomás Antonio
author Valdivieso, Ángel Gabriel
author_facet Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Massip Copiz, María Macarena
Cancio, Carla E.
Asensio, Cristian J. A.
Mori, Consuelo
Santa Coloma, Tomás Antonio
author_role author
author2 Clauzure, Mariángeles
Massip Copiz, María Macarena
Cancio, Carla E.
Asensio, Cristian J. A.
Mori, Consuelo
Santa Coloma, Tomás Antonio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CFTR
FIBROSIS QUISTICA
INFLAMACION
CELULAS EPITELIALES
INTESTINOS
ACIDO LACTICO
topic CFTR
FIBROSIS QUISTICA
INFLAMACION
CELULAS EPITELIALES
INTESTINOS
ACIDO LACTICO
dc.description.none.fl_txt_mv Fil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Valdivieso, Ángel Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Clauzure, Mariángeles. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Clauzure, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Massip Copiz, María Macarena. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Massip Copiz, María Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cancio, Carla E. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cancio, Carla E. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Asensio, Cristian. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Asensio, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mori, Consuelo. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Mori, Consuelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Santa Coloma, Tomás Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Asbtract: Mutations in the gene encoding the CFTR chloride channel produce cystic fibrosis (CF). CF patients are more susceptible to bacterial infections in lungs. The most accepted hypothesis sustains that a reduction in the airway surface liquid (ASL) volume favor infections. Alternatively, it was postulated that a reduced HCO3- transport through CFTR leads to a decreased ASL pH, favoring bacterial colonization. The issue is controversial, since recent data from cultured primary cells and CF children showed normal pH values in the ASL. We have reported previously a decreased mitochondrial Complex I (mCx-I) activity in cultured cells with impaired CFTR activity. Thus, we hypothesized that the reduced mCx-I activity could lead to increased lactic acid production (Warburg-like effect) and reduced extracellular pH (pHe). In agreement with this idea, we report here that cells with impaired CFTR function (intestinal Caco-2/pRS26, transfected with an shRNA-CFTR, and lung IB3-1 CF cells) have a decreased pHe. These cells showed increased lactate dehydrogenase (LDH) activity, LDH-A expression, and lactate secretion. Similar effects were reproduced in control cells stimulated with recombinant IL-1β. The c-Src and JNK inhibitors PP2 and SP600125 were able to increase the pHe, although the differences between control and CFTR-impaired cells were not fully compensated. Noteworthy, the LDH inhibitor oxamate completely restored the pHe of the intestinal Caco-2/pRS26 cells and have a significant effect in lung IB3-1 cells; therefore, an increased lactic acid secretion seems to be the key factor that determine a reduced pHe in these epithelial cells.
description Fil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://repositorio.uca.edu.ar/handle/123456789/9596
1420-9071 (online)
1420-682X (impreso)
10.1007/s00018-018-3001-y
30599064
Valdivieso, A.G. et al. Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion [en línea]. Cellular and Molecular Life Sciences. 2019, 76. doi:10.1007/s00018-018-3001-y Disponible en: https://repositorio.uca.edu.ar/handle/123456789/9596
url https://repositorio.uca.edu.ar/handle/123456789/9596
identifier_str_mv 1420-9071 (online)
1420-682X (impreso)
10.1007/s00018-018-3001-y
30599064
Valdivieso, A.G. et al. Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion [en línea]. Cellular and Molecular Life Sciences. 2019, 76. doi:10.1007/s00018-018-3001-y Disponible en: https://repositorio.uca.edu.ar/handle/123456789/9596
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/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Cellular and Molecular Life Sciences. 2019, 76
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
_version_ 1836638350149156864
score 13.22299

Publicaciones similares