Phenotypic and metabolic features of mouse diaphragm and gastrocnemius muscles in chronic lung carcinogenesis: influence of underlying emphysema

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• dc.contributor.author Salazar Degracia, Annaca
• dc.contributor.author Blanco, Davidca
• dc.contributor.author Vilà-Ubach, Mònicaca
• dc.contributor.author de Biurrun, Gabrielca
• dc.contributor.author Ortiz de Solórzano, Carlosca
• dc.contributor.author Montuenga, Luisca
• dc.contributor.author Barreiro Portela, Estherca
• dc.date.accessioned 2016-11-15T11:51:09Z
• dc.date.available 2016-11-15T11:51:09Z
• dc.date.issued 2016ca
• dc.description.abstract Background: Muscle wasting negatively impacts the progress of chronic diseases such as lung cancer (LC) and emphysema, which are in turn interrelated. Objectives: We hypothesized that muscle atrophy and body weight loss may develop in an experimental mouse model of lung carcinogenesis, that the profile of alterations in muscle fiber phenotype (fiber type composition and morphometry, muscle structural alterations, and nuclear apoptosis), and in muscle metabolism are similar in both respiratory and limb muscles of the tumor-bearing mice, and that the presence of underlying emphysema may influence those events. Methods: Diaphragm and gastrocnemius muscles of mice with urethane-induced lung cancer (LC-U) with and without elastase-induced emphysema (E–U) and non-exposed controls (N = 8/group) were studied: fiber type composition, morphometry, muscle abnormalities, apoptotic nuclei (immunohistochemistry), and proteolytic and autophagy markers (immunoblotting) at 20- and 35-week exposure times. In the latter cohort, structural contractile proteins, creatine kinase (CK), peroxisome proliferator-activated receptor (PPAR) expression, oxidative stress, and inflammation were also measured. Body and muscle weights were quantified (baseline, during follow-up, and sacrifice). Results: Compared to controls, in U and E–U mice, whole body, diaphragm and gastrocnemius weights were reduced. Additionally, both in diaphragm and gastrocnemius, muscle fiber cross-sectional areas were smaller, structural abnormalities, autophagy and apoptotic nuclei were increased, while levels of actin, myosin, CK, PPARs, and antioxidants were decreased, and muscle proteolytic markers did not vary among groups. Conclusions: In this model of lung carcinogenesis with and without emphysema, reduced body weight gain and muscle atrophy were observed in respiratory and limb muscles of mice after 20- and 35-week exposure times most likely through increased nuclear apoptosis and autophagy. Underlying emphysema induced a larger reduction in the size of slow- and fast-twitch fibers in the diaphragm of U and E–U mice probably as a result of the greater inspiratory burden imposed onto this muscle.
• dc.description.sponsorship This study has been supported by CIBERES, RTICC RD12/0036/0040, PI07/0751 (FEDER), PI11/02029 (FEDER), PI13/08006 (FEDER), PI14/00713 (FEDER), and MINECO DPI2015-64221-C2-2 SEPAR 2009. None of the funding bodies have played any role in the data collection, analysis, interpretation of the results, or manuscript writing.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Salazar-Degracia A, Blanco D, Vilà-Ubach M, de Biurrun G, Ortiz de Solórzano C, Montuenga L M, Barreiro E. Phenotypic and metabolic features of mouse diaphragm and gastrocnemius muscles in chronic lung carcinogenesis: influence of underlying emphysema. Journal of Translation Medicine. 2016; 14(1):244. DOI: 10.1186/s12967-016-1003-9ca
• dc.identifier.doi http://dx.doi.org/10.1186/s12967-016-1003-9
• dc.identifier.issn 1479-5876ca
• dc.identifier.uri http://hdl.handle.net/10230/27513
• dc.language.iso engca
• dc.publisher BioMed Centralca
• dc.relation.ispartof Journal of Translation Medicine. 2016; 14(1):244
• dc.rights © 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Lung carcinogenesis-induced muscle mass loss
• dc.subject.keyword Underlying emphysema
• dc.subject.keyword Respiratory and limb muscle atrophy and structural abnormalities
• dc.subject.keyword Muscle apoptotic nuclei
• dc.subject.keyword Muscle-specific proteins
• dc.subject.keyword PPARs proteolytic and autophagy markers
• dc.title Phenotypic and metabolic features of mouse diaphragm and gastrocnemius muscles in chronic lung carcinogenesis: influence of underlying emphysemaca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca