Por favor, use este identificador para citar o enlazar este ítem:
https://doi.org/10.1093/glycob/cwab087
Twittear
Título: | Dissecting the transcriptional program of phosphomannomutase 2-deficient cells: Lymphoblastoide B cell lines as a valuable model for congenital disorders of glycosylation studies |
Fecha de publicación: | 2022 |
Editorial: | Oxford University Press |
Cita bibliográfica: | Glicobiology 2022, Volumen: 32, Número: 2, Páginas: 84-100 |
ISSN: | Print: 0959-6658 Electronic: 1460-2423 |
Materias relacionadas: | CDU::5 - Ciencias puras y naturales |
Palabras clave: | B-lymphoblastoid cells CA2 Congenital disorders of glycosylation Gene expression profile PMM2-CDG |
Resumen: | Congenital disorders of glycosylation (CDG) include 150 disorders constituting in genetically and clinically heterogeneous diseases, showing significant glycoprotein hypoglycosylation that leads to pathological consequences on multiple organs and systems whose underlying mechanisms are not yet understood. A few cellular and animal models have been used to study specific CDG characteristics, although they have given limited information due to the few CDG mutations tested and the still missing comprehensive molecular and cellular basic research. Here, we provide specific gene expression profiles, based on ribonucleic acid (RNA) microarray analysis, together with some biochemical and cellular characteristics of a total of nine control Epstein– Barr virus-transformed lymphoblastoid B cell lines (B-LCL) and 13 CDG B-LCL from patients carrying severe mutations in the phosphomannomutase 2 (PMM2) gene, strong serum protein hypoglycosylation and neurological symptoms. Significantly dysregulated genes in PMM2-CDG cells included those regulating stress responses, transcription factors, glycosylation, motility, cell junction and, importantly, those related to development and neuronal differentiation and synapse, such as carbonic anhydrase 2 (CA2) and ADAM23. PMM2-CDG-associated biological consequences involved the unfolded protein response, RNA metabolism and the endoplasmic reticulum, Golgi apparatus and mitochondria components. Changes in the transcriptional and CA2 protein levels are consistent with the CDG physiopathology. These results demonstrate the global transcriptional impact in phosphomannomutase 2-deficient cells, reveal CA2 as a potential cellular biomarker and confirm B-LCL as an advantageous model for CDG studies. |
Autor/es principal/es: | Parrado, Antonio Rubio, Gonzalo Serrano, Mercedes De la Morena-Barrio, María Eugenia Ibáñez-Micó, Salvador Ruiz-Lafuente, Natalia Schwartz-Albiez, Reinhard Esteve-Solé, Ana Alsina, Laia Corral, Javier Hernández-Caselles, Trinidad |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular "B" e Inmunología |
URI: | http://hdl.handle.net/10201/138886 |
DOI: | https://doi.org/10.1093/glycob/cwab087 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 17 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Descripción: | ©<2022>. This manuscript version is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the, Accepted, version of a Published Work that appeared in final form in Glycobiology. To access the final edited and published work see: https://doi.org/10.1093/glycob/cwab087 |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
cwab087-1 final.pdf | 1,42 MB | Adobe PDF | Visualizar/Abrir |
Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons