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Increased myogenic and protein turnover signaling in skeletal muscle of chronic obstructive pulmonary disease patients with sarcopeniaKneppers, Anita E. M. ...Sarcopenia was recently recognized as an independent condition by an International Classification of Diseases, Tenth Revision, Clinical Modification code, and is a frequently observed comorbidity in ... chronic obstructive pulmonary disease (COPD). Muscle mass is primarily dictated by the balance between protein degradation and synthesis, but their relative contribution to sarcopenia is unclear. We aimed to assess potential differential molecular regulation of protein degradation and synthesis, as well as myogenesis, in the skeletal muscle of COPD patients with and without sarcopenia. Muscle biopsies were obtained from the vastus lateralis muscle. Patients with COPD were clustered based on sarcopenia defined by low appendicular skeletal muscle mass index (nonsarcopenic COPD, n = 53; sarcopenic COPD, n = 39), and compared with healthy nonsarcopenic controls (n = 13). The mRNA and protein expression of regulators and mediators of ubiquitin-proteasome system (UPS), autophagy-lysosome system (autophagy), and protein synthesis were analyzed. Furthermore, mRNA expression of myogenesis markers was assessed. UPS signaling was unaltered, whereas indices of UPS regulation (eg, FOXO1 protein; p-FOXO3/FOXO3), autophagy signaling (eg, LC3BII/I; p-ULK1[Ser757]/ULK1), and protein synthesis signaling (eg, AKT1; p-GSK3B/GSK3B; p-4E-BP1/4E-BP1) were increased in COPD. These alterations were even more pronounced in COPD patients with sarcopenia (eg, FOXO1 protein; p-FOXO1/FOXO1; LC3BII/I; p-ULK(Ser555); p-AKT1/AKT1; AKT1; p-4E-BP1). Furthermore, myogenic signaling (eg, MYOG) was increased in COPD despite a concomitant increase of myostatin (MSTN) mRNA expression, with no difference between sarcopenic and nonsarcopenic COPD patients. Together with elevated myogenic signaling, the increase in muscle protein turnover signaling in COPD, which is even more prominent in COPD patients with sarcopenia, reflects molecular alterations associated with muscle repair and remodeling.Source: Journal of the American Medical Directors Association. - ISSN 1525-8610 (Vol . 18, iss. 7, 2017, str. 637.e1-637.e11)Type of material - article, component partPublish date - 2017Language - englishCOBISS.SI-ID - 4419441
Author
Kneppers, Anita E. M. |
Langen, Ramon C. J. |
Gosker, Harry Reinier, 1973- |
Verdijk, Lex B. |
Čebron Lipovec, Nanča |
Leermakers, Pieter A. |
Kelders, Marco C. J. M. |
Theije, Chiel C. de |
Omersa, Daniel |
Lainščak, Mitja |
Schols, Annemie M. W. J.
Topics
muscular atrophy |
protein biosynthesis |
proteolysis |
myogenic differentiation |
long-term care
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Kneppers, Anita E. M. | ![]() |
Langen, Ramon C. J. | ![]() |
Gosker, Harry Reinier, 1973- | ![]() |
Verdijk, Lex B. | ![]() |
Čebron Lipovec, Nanča | 34096 |
Leermakers, Pieter A. | ![]() |
Kelders, Marco C. J. M. | ![]() |
Theije, Chiel C. de | ![]() |
Omersa, Daniel | 36478 |
Lainščak, Mitja | 22680 |
Schols, Annemie M. W. J. | ![]() |
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