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...

Descripción completa

Guardado en:
Detalles Bibliográficos
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
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
Descripción
Sumario: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.

Ejemplares similares