Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells

Abstract: Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It has been postulated that reduced HCO3− transport through CFTR may lead to a decreased airway surface liquid pH. In contrast, others have reported no changes in the extrace...

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Autores principales: Massip Copiz, María Macarena, Valdivieso, Ángel Gabriel, Clauzure, Mariángeles, Mori, Consuelo, Asensio, Cristian J. A., Aguilar, María de los Angeles, Santa Coloma, Tomás Antonio
Formato: Artículo
Lenguaje:Inglés
Publicado: 2022
Materias:
FIBROSIS QUISTICA
GENES
SISTEMA RESPIRATORIO
CELULAS
LACTATO DESHIDROGENASA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/14036
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Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-14036
record_format dspace
spelling I33-R139-123456789-140362024-03-07T11:35:54Z Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells Massip Copiz, María Macarena Valdivieso, Ángel Gabriel Clauzure, Mariángeles Mori, Consuelo Asensio, Cristian J. A. Aguilar, María de los Angeles Santa Coloma, Tomás Antonio FIBROSIS QUISTICA GENES SISTEMA RESPIRATORIO CELULAS LACTATO DESHIDROGENASA Abstract: Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It has been postulated that reduced HCO3− transport through CFTR may lead to a decreased airway surface liquid pH. In contrast, others have reported no changes in the extracellular pH (pHe). We have recently reported that in carcinoma Caco-2/pRS26 cells (transfected with short hairpin RNA for CFTR) or CF lung epithelial IB3-1 cells, the mutation in CFTR decreased mitochondrial complex I activity and increased lactic acid production, owing to an autocrine IL-1β loop. The secreted lactate accounted for the reduced pHe, because oxamate fully restored the pHe. These effects were attributed to the IL-1β autocrine loop and the downstream signaling kinases c-Src and JNK. Here we show that the pHe of IB3-1 cells can be restored to normal values (∼7.4) by incubation with the epidermal growth factor receptor (EGFR, HER1, ErbB1) inhibitors AG1478 and PD168393. PD168393 fully restored the pHe values of IB3-1 cells, suggesting that the reduced pHe is mainly due to increased EGFR activity and lactate. Also, in IB3-1 cells, lactate dehydrogenase A mRNA, protein expression, and activity are downregulated when EGFR is inhibited. Thus, a constitutive EGFR activation seems to be responsible for the reduced pHe in IB3-1 cells. 2022-05-27T13:30:26Z 2022-05-27T13:30:26Z 2021 Artículo Massip Copiz, M. M. et al. Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells [en línea]. Postprint de artículo publicado en Biochemistry and Cell Biology. 2021, 99 (4). doi: 10.1139/bcb-2020-0522. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14036 0829-8211 (impreso) 1208-6002 (on line) https://repositorio.uca.edu.ar/handle/123456789/14036 10.1139/bcb-2020-0522 33481676 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Postprint de artículo publicado en Biochemistry and Cell Biology. 2021, 99 (4)
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic FIBROSIS QUISTICA
GENES
SISTEMA RESPIRATORIO
CELULAS
LACTATO DESHIDROGENASA
spellingShingle FIBROSIS QUISTICA
GENES
SISTEMA RESPIRATORIO
CELULAS
LACTATO DESHIDROGENASA
Massip Copiz, María Macarena
Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Mori, Consuelo
Asensio, Cristian J. A.
Aguilar, María de los Angeles
Santa Coloma, Tomás Antonio
Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells
topic_facet FIBROSIS QUISTICA
GENES
SISTEMA RESPIRATORIO
CELULAS
LACTATO DESHIDROGENASA
description Abstract: Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It has been postulated that reduced HCO3− transport through CFTR may lead to a decreased airway surface liquid pH. In contrast, others have reported no changes in the extracellular pH (pHe). We have recently reported that in carcinoma Caco-2/pRS26 cells (transfected with short hairpin RNA for CFTR) or CF lung epithelial IB3-1 cells, the mutation in CFTR decreased mitochondrial complex I activity and increased lactic acid production, owing to an autocrine IL-1β loop. The secreted lactate accounted for the reduced pHe, because oxamate fully restored the pHe. These effects were attributed to the IL-1β autocrine loop and the downstream signaling kinases c-Src and JNK. Here we show that the pHe of IB3-1 cells can be restored to normal values (∼7.4) by incubation with the epidermal growth factor receptor (EGFR, HER1, ErbB1) inhibitors AG1478 and PD168393. PD168393 fully restored the pHe values of IB3-1 cells, suggesting that the reduced pHe is mainly due to increased EGFR activity and lactate. Also, in IB3-1 cells, lactate dehydrogenase A mRNA, protein expression, and activity are downregulated when EGFR is inhibited. Thus, a constitutive EGFR activation seems to be responsible for the reduced pHe in IB3-1 cells.
format Artículo
author Massip Copiz, María Macarena
Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Mori, Consuelo
Asensio, Cristian J. A.
Aguilar, María de los Angeles
Santa Coloma, Tomás Antonio
author_facet Massip Copiz, María Macarena
Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Mori, Consuelo
Asensio, Cristian J. A.
Aguilar, María de los Angeles
Santa Coloma, Tomás Antonio
author_sort Massip Copiz, María Macarena
title Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells
title_short Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells
title_full Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells
title_fullStr Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells
title_full_unstemmed Epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells
title_sort epidermal growth factor receptor activity upregulates lactate dehydrogenase a expression, lactate dehydrogenase activity, and lactate secretion in cultured ib3-1 cystic fibrosis lung epithelial cells
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/14036
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