Please use this identifier to cite or link to this item: https://repositorio.uca.edu.ar/handle/123456789/14036
Título : EGFR activity upregulates lactate dehydrogenase A (LDHA) expression, LDH activity, and 1 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 
Aguilar, María Á. 
Santa Coloma, Tomás Antonio 
Palabras clave : FIBROSIS QUISTICAGENESSISTEMA RESPIRATORIOCELULASLACTATO DESHIDROGENASA
Fecha de publicación : 2021
Cita : Massip Copiz, M. M. et al. EGFR activity upregulates lactate dehydrogenase A (LDHA) expression, LDH activity, and 1 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
Appears in Collections:Artículos

Files in This Item:
File Description SizeFormat
EGFR-activity-upregulates-lactate.pdf739,67 kBAdobe PDFThumbnail
View/Open
Show full item record

Page view(s)

19
checked on Aug 9, 2022

Download(s)

10
checked on Aug 9, 2022

Google ScholarTM

Check


Altmetric


This item is licensed under a Creative Commons License Creative Commons