Reduced myotube diameter, atrophic signalling and elevated oxidative stress in cultured satellite cells from COPD patients

• Published in: Journal of cellular and molecular medicine Vol. 19; no. 1; pp. 175 - 186
• Main Authors: Pomiès, Pascal, Rodriguez, Julie, Blaquière, Marine, Sedraoui, Sami, Gouzi, Fares, Carnac, Gilles, Laoudj‐Chenivesse, Dalila, Mercier, Jacques, Préfaut, Christian, Hayot, Maurice
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2015; Wiley Open Access; Blackwell Publishing Ltd
• Subjects: Aged; AKT protein; Antioxidants; Atrophy; Biomarkers - metabolism; Biopsy; Case-Control Studies; Cell culture; Cell differentiation; Cell Differentiation - drug effects; Cell Fusion; Cell Proliferation - drug effects; Cell Size - drug effects; Cells, Cultured; Cellular Biology; cellular model; Chronic obstructive pulmonary disease; Collagen; COPD; Cytology; Deoxyribonucleic acid; Disease; DNA; DNA methylation; Epigenetics; Exercise; Female; Gene expression; Human health and pathology; Humans; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Hypertrophy; Hypotheses; Life Sciences; Lipid peroxidation; Lipid Peroxidation - drug effects; Lung diseases; Male; Middle Aged; Mitochondrial DNA; Morphology; muscle dysfunction; Muscle Fibers, Skeletal - pathology; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscles; Muscular Atrophy - pathology; Musculoskeletal system; Myoblasts; Myoblasts - drug effects; Myoblasts - pathology; Myostatin; Myotubes; Obstructive lung disease; Original; Oxidative stress; Oxidative Stress - drug effects; Patients; Phenotypes; Physical characteristics; Physical fitness; Physiology; Protein Biosynthesis - drug effects; Protein Carbonylation - drug effects; Pulmonary Disease, Chronic Obstructive - pathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Satellite cells; Satellite Cells, Skeletal Muscle - drug effects; Satellite Cells, Skeletal Muscle - pathology; Signal Transduction - drug effects; Skeletal muscle; Studies; Subcellular Processes; Tissues and Organs; France; United States > US; atrophy; cellular model; muscle dysfunction; oxidative stress; COPD; satellite cells
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.12390

The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated. Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown. Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status. Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals. We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2O2 in cultured myoblasts and/or myotubes. Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes. Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin‐1 (myoblasts: P = 0.050), and a decreased phospho‐AKT/AKT ratio (myoblasts: P = 0.022). Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress. Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles. We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models.