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

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...

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Autores principales: Valdivieso, Ángel Gabriel, Clauzure, Mariángeles, Massip Copiz, María Macarena, Cancio, Carla E., Asensio, Cristian, Mori, Consuelo, Santa Coloma, Tomás Antonio
Formato: Artículo
Lenguaje:Inglés
Publicado: Springer 2020
Materias:
CFTR
FIBROSIS QUISTICA
INFLAMACION
CELULAS EPITELIALES
INTESTINOS
ACIDO LACTICO
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/9596
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-9596
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic CFTR
FIBROSIS QUISTICA
INFLAMACION
CELULAS EPITELIALES
INTESTINOS
ACIDO LACTICO
spellingShingle CFTR
FIBROSIS QUISTICA
INFLAMACION
CELULAS EPITELIALES
INTESTINOS
ACIDO LACTICO
Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Massip Copiz, María Macarena
Cancio, Carla E.
Asensio, Cristian
Mori, Consuelo
Santa Coloma, Tomás Antonio
Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
topic_facet CFTR
FIBROSIS QUISTICA
INFLAMACION
CELULAS EPITELIALES
INTESTINOS
ACIDO LACTICO
description 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.
format Artículo
author Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Massip Copiz, María Macarena
Cancio, Carla E.
Asensio, Cristian
Mori, Consuelo
Santa Coloma, Tomás Antonio
author_facet Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Massip Copiz, María Macarena
Cancio, Carla E.
Asensio, Cristian
Mori, Consuelo
Santa Coloma, Tomás Antonio
author_sort Valdivieso, Ángel Gabriel
title Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion
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
publisher Springer
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/9596
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