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Título : | 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 | Autor : | Massip Copiz, María Macarena Valdivieso, Ángel Gabriel Clauzure, Mariángeles Mori, Consuelo Asensio, Cristian J. A. Aguilar, María de los Angeles Santa Coloma, Tomás Antonio |
Palabras clave : | FIBROSIS QUISTICA; GENES; SISTEMA RESPIRATORIO; CELULAS; LACTATO DESHIDROGENASA | Fecha de publicación : | 2021 | Cita : | 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 | Resumen : | 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. | URI : | https://repositorio.uca.edu.ar/handle/123456789/14036 | ISSN : | 0829-8211 (impreso) 1208-6002 (on line) |
Disciplina: | MEDICINA | DOI: | 10.1139/bcb-2020-0522 | Derechos: | Acceso abierto |
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