title: Reduced myotube diameter, atrophic signalling and elevated oxidative stress in cultured satellite cells from COPD patients.
abstract: 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 H2 O2 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.
authors.affiliation: INSERM U-1046, University Montpellier I, University Montpellier II, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pomiès
authors.forename: Julie
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Marine
authors.initials: M
authors.lastname: Blaquière
authors.forename: Sami
authors.initials: S
authors.lastname: Sedraoui
authors.forename: Fares
authors.initials: F
authors.lastname: Gouzi
authors.forename: Gilles
authors.initials: G
authors.lastname: Carnac
authors.forename: Dalila
authors.initials: D
authors.lastname: Laoudj-Chenivesse
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.forename: Christian
authors.initials: C
authors.lastname: Préfaut
authors.forename: Maurice
authors.initials: M
authors.lastname: Hayot
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009133:Muscular Atrophy / Q000473:pathology*; D032446:Myoblasts / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D009124:Muscle Proteins; D012333:RNA, Messenger; D006861:Hydrogen Peroxide
keywords: COPD; atrophy; cellular model; muscle dysfunction; oxidative stress; satellite cells