Welcome to the UPF Digital Repository

Endoplasmic reticulum stress and unfolded protein response in diaphragm muscle dysfunction of patients with stable chronic obstructive pulmonary disease

Show simple item record

dc.contributor.author Barreiro Portela, Esther
dc.contributor.author Salazar Degracia, Anna
dc.contributor.author Sancho Muñoz, Antonio
dc.contributor.author Aguiló Espases, Rafael
dc.contributor.author Rodríguez-Fuster, Alberto
dc.contributor.author Gea Guiral, Joaquim
dc.date.accessioned 2020-02-05T08:25:16Z
dc.date.issued 2019
dc.identifier.citation Barreiro E, Salazar-Degracia A, Sancho-Muñoz A, Aguiló R, Rodríguez-Fuster A, Gea J. Endoplasmic reticulum stress and unfolded protein response in diaphragm muscle dysfunction of patients with stable chronic obstructive pulmonary disease. J Appl Physiol (1985). 2019;126(6):1572-86. DOI: 10.1152/japplphysiol.00670.2018
dc.identifier.issn 8750-7587
dc.identifier.uri http://hdl.handle.net/10230/43481
dc.description.abstract Respiratory muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). Chronic contractile activity induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in animals (animals and humans). We hypothesized that the respiratory muscle dysfunction associated with COPD may upregulate ER stress and UPR expression in diaphragm of stable patients with different degrees of airway obstruction and normal body composition. In diaphragm muscle specimens of patients with mild and moderate-to-severe COPD with preserved body composition and non-COPD controls (thoracotomy because of lung localized neoplasms), expression of protein misfolding (ER stress) and UPR markers, proteolysis and apoptosis (qRT-PCR and immunoblotting), and protein aggregates (lipofuscin, histology) were quantified. All patients and non-COPD controls were also clinically evaluated: lung and muscle functions and exercise capacity. Compared with non-COPD controls, patients exhibited mild and moderate-to-severe airflow limitation and diffusion capacity and impaired exercise tolerance and diaphragm strength. Moreover, compared with the controls, in the diaphragm of the COPD patients, slow-twitch fiber proportions increased, gene expression but not protein levels of protein disulfide isomerase family A member 3 and phosphatidylinositol 3-kinase catalytic subunit type 3 were upregulated, and no significant differences were found in markers of UPR transmembrane receptor pathways (activating transcription factor-6, inositol-requiring enzyme-1α, and protein kinase-like ER kinase), lipofuscin aggregates, proteolysis, or apoptosis. In stable COPD patients with a wide range of disease severity, reduced diaphragm force of contraction, and normal body composition, ER stress and UPR signaling were not induced in the main respiratory muscle. These findings imply that ER stress and UPR are probably not involved in the documented diaphragm muscle dysfunction (reduced strength) observed in all the study patients, even in those with severe airflow limitation. Hence, in stable COPD patients with normal body composition, therapeutic strategies targeted to treat diaphragm muscle dysfunction should not include UPR modulators, even in those with a more advanced disease. NEW & NOTEWORTHY In stable chronic obstructive pulmonary disease patients with a wide range of disease severity, diaphragm muscle weakness, and normal body composition, endoplasmic reticulum stress and unfolded protein response (UPR) signaling were not induced in the main respiratory muscle. These findings imply that endoplasmic reticulum stress and UPR are not involved in the documented diaphragm muscle dysfunction observed in the study patients, even in those with severe airflow limitation. In stable chronic obstructive pulmonary disease patients with normal body composition, therapeutic strategies should not include UPR modulators.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher American Physiological Society
dc.relation.ispartof Journal of Applied Physiology. 2019;126(6):1572-86
dc.rights © 2019 the American Physiological Society. http://dx.doi.org/10.1152/japplphysiol.00670.2018
dc.title Endoplasmic reticulum stress and unfolded protein response in diaphragm muscle dysfunction of patients with stable chronic obstructive pulmonary disease
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1152/japplphysiol.00670.2018
dc.subject.keyword COPD
dc.subject.keyword Diaphragm
dc.subject.keyword Endoplasmic reticulum stress
dc.subject.keyword Respiratory muscle dysfunction
dc.subject.keyword Unfolded protein response
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

In collaboration with Compliant to Partaking