Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia

Anita E. M. Kneppers; Ramon C. J. Langen; Harry R. Gosker; Lex B. Verdijk; Nanca Cebron Lipovec; Pieter A. Leermakers; Marco C. J. M. Kelders; Chiel C. de Theije; Daniel Omersa; Mitja Lainscak; Annemie M. W. J. Schols

doi:10.1016/j.jamda.2017.04.016

Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia

Anita E. M. Kneppers
, Ramon C. J. Langen
, Harry R. Gosker
, Lex B. Verdijk
, Nanca Cebron Lipovec
, Pieter A. Leermakers
, Marco C. J. M. Kelders
, Chiel C. de Theije
, Daniel Omersa
, Mitja Lainscak
, Annemie M. W. J. Schols^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Original language	English
Pages (from-to)	637.e1-637.e11
Number of pages	11
Journal	Journal of the American Medical Directors Association
Volume	18
Issue number	7
DOIs	https://doi.org/10.1016/j.jamda.2017.04.016
Publication status	Published - 1 Jul 2017

Keywords

Muscular atrophy
protein biosynthesis
proteolysis
myogenic differentiation
MYOBLAST DIFFERENTIATION
NUTRITIONAL DEPLETION
ECCENTRIC EXERCISE
OXIDATIVE STRESS
SATELLITE CELLS
MODERATE COPD
QUADRICEPS
AUTOPHAGY
EXPRESSION
ATROPHY

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10.1016/j.jamda.2017.04.016

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Kneppers, A. E. M., Langen, R. C. J., Gosker, H. R., Verdijk, L. B., Lipovec, N. C., Leermakers, P. A., Kelders, M. C. J. M., de Theije, C. C., Omersa, D., Lainscak, M., & Schols, A. M. W. J. (2017). Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia. Journal of the American Medical Directors Association, 18(7), 637.e1-637.e11. https://doi.org/10.1016/j.jamda.2017.04.016

@article{88875034d89e47d6acd7a5351d5bc152,

title = "Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia",

abstract = "Background: 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.Objective: 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.Methods: 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.Results: 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.Conclusion: 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. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.",

keywords = "Muscular atrophy, protein biosynthesis, proteolysis, myogenic differentiation, MYOBLAST DIFFERENTIATION, NUTRITIONAL DEPLETION, ECCENTRIC EXERCISE, OXIDATIVE STRESS, SATELLITE CELLS, MODERATE COPD, QUADRICEPS, AUTOPHAGY, EXPRESSION, ATROPHY",

author = "Kneppers, \{Anita E. M.\} and Langen, \{Ramon C. J.\} and Gosker, \{Harry R.\} and Verdijk, \{Lex B.\} and Lipovec, \{Nanca Cebron\} and Leermakers, \{Pieter A.\} and Kelders, \{Marco C. J. M.\} and \{de Theije\}, \{Chiel C.\} and Daniel Omersa and Mitja Lainscak and Schols, \{Annemie M. W. J.\}",

year = "2017",

month = jul,

day = "1",

doi = "10.1016/j.jamda.2017.04.016",

language = "English",

volume = "18",

pages = "637.e1--637.e11",

journal = "Journal of the American Medical Directors Association",

issn = "1525-8610",

publisher = "Elsevier Inc.",

number = "7",

}

Kneppers, AEM, Langen, RCJ , Gosker, HR , Verdijk, LB, Lipovec, NC, Leermakers, PA, Kelders, MCJM , de Theije, CC, Omersa, D, Lainscak, M & Schols, AMWJ 2017, 'Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia', Journal of the American Medical Directors Association, vol. 18, no. 7, pp. 637.e1-637.e11. https://doi.org/10.1016/j.jamda.2017.04.016

Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia. / Kneppers, Anita E. M.; Langen, Ramon C. J.; Gosker, Harry R. et al.
In: Journal of the American Medical Directors Association, Vol. 18, No. 7, 01.07.2017, p. 637.e1-637.e11.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia

AU - Kneppers, Anita E. M.

AU - Langen, Ramon C. J.

AU - Gosker, Harry R.

AU - Verdijk, Lex B.

AU - Lipovec, Nanca Cebron

AU - Leermakers, Pieter A.

AU - Kelders, Marco C. J. M.

AU - de Theije, Chiel C.

AU - Omersa, Daniel

AU - Lainscak, Mitja

AU - Schols, Annemie M. W. J.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Background: 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.Objective: 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.Methods: 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.Results: 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.Conclusion: 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. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

AB - Background: 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.Objective: 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.Methods: 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.Results: 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.Conclusion: 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. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

KW - Muscular atrophy

KW - protein biosynthesis

KW - proteolysis

KW - myogenic differentiation

KW - MYOBLAST DIFFERENTIATION

KW - NUTRITIONAL DEPLETION

KW - ECCENTRIC EXERCISE

KW - OXIDATIVE STRESS

KW - SATELLITE CELLS

KW - MODERATE COPD

KW - QUADRICEPS

KW - AUTOPHAGY

KW - EXPRESSION

KW - ATROPHY

U2 - 10.1016/j.jamda.2017.04.016

DO - 10.1016/j.jamda.2017.04.016

M3 - Article

C2 - 28578881

SN - 1525-8610

VL - 18

SP - 637.e1-637.e11

JO - Journal of the American Medical Directors Association

JF - Journal of the American Medical Directors Association

IS - 7

ER -

Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia

Abstract

Keywords

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