Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation
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- dc.contributor.author Peinado, Victor I.
- dc.contributor.author Guitart, Maria
- dc.contributor.author Blanco, Isabel
- dc.contributor.author Tura-Ceide, Olga
- dc.contributor.author Paul, Tanja
- dc.contributor.author Barberà, Joan Albert
- dc.contributor.author Barreiro Portela, Esther
- dc.date.accessioned 2023-09-06T06:36:23Z
- dc.date.available 2023-09-06T06:36:23Z
- dc.date.issued 2023
- dc.description.abstract Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) is characterized by a significant reduction in muscle strength and endurance. Preclinical studies show that stimulation of the soluble guanylate cyclase (sGC)-cGMP pathway attenuates muscle mass loss and prevents cigarette smoke-induced oxidative stress, indicating that pharmacological activation of the guanylyl cyclase pathway in COPD may provide a beneficial therapeutic strategy that reaches beyond the lung. In this study, conducted in an animal model of COPD, we first set out to assess the effect of cigarette smoke (CS) on biomarkers of muscle fatigue, such as protein degradation and its transcriptional regulation, in two types of muscles with different energy demands, i.e., the diaphragm and the gastrocnemius muscle of the limbs. Second, we evaluated the administration of an sGC stimulator on these markers to study the potential efficacy of such treatment in the recovery of skeletal muscle function. Exposure to CS led to weight loss, which was associated in the gastrocnemius with increased levels of proteolytic markers of muscle atrophy (MURF-1, Atrogin-1, proteasome C8 subunit 20 s, and total protein ubiquitination), whereas the size of fast-twitch muscle fibers decreased significantly. Long-term treatment with the sGC stimulator BAY 41-2272 resulted in a significant reduction in gastrocnemius levels of the aforementioned proteolytic markers, concomitant with a weight recovery and increased cGMP levels. Remarkably, levels of some of the analyzed biomarkers differed between respiratory and limb muscles. In conclusion, targeting sGC might exert beneficial effects on muscle alterations in patients with COPD.
- dc.format.mimetype application/pdf
- dc.identifier.citation Ivo Peinado V, Guitart M, Blanco I, Tura-Ceide O, Paul T, Barberà JA, Barreiro E. Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation. Am J Physiol Lung Cell Mol Physiol. 2023;324(5):L677-93. DOI: 10.1152/ajplung.00258.2022
- dc.identifier.doi http://dx.doi.org/10.1152/ajplung.00258.2022
- dc.identifier.issn 1040-0605
- dc.identifier.uri http://hdl.handle.net/10230/57821
- dc.language.iso eng
- dc.publisher American Physiological Society
- dc.relation.ispartof Am J Physiol Lung Cell Mol Physiol. 2023;324(5):L677-93
- dc.rights © 2023 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0. Published by the American Physiological Society.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword COPD
- dc.subject.keyword cGMP
- dc.subject.keyword Muscle atrophy
- dc.subject.keyword Pharmacology
- dc.title Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion