TY - JOUR
T1 - Impaired adaptive response to mechanical overloading in dystrophic skeletal muscle
AU - Joanne, Pierre
AU - Hourde, Christophe
AU - Ochala, Julien
AU - Cauderan, Yvain
AU - Medja, Fadia
AU - Vignaud, Alban
AU - Mouisel, Etienne
AU - Hadj-Said, Wahiba
AU - Arandel, Ludovic
AU - Garcia, Luis
AU - Goyenvalle, Aurelie
AU - Mounier, Remi
AU - Zibroba, Daria
AU - Sakamato, Kei
AU - Butler-Browne, Gillian
AU - Agbulut, Onnik
AU - Ferry, Arnaud
PY - 2012
Y1 - 2012
N2 - Dystrophin contributes to force transmission and has a protein-scaffolding role for a variety of signaling complexes in skeletal muscle. In the present study, we tested the hypothesis that the muscle adaptive response following mechanical overloading (ML) would be decreased in MDX dystrophic muscle lacking dystrophin. We found that the gains in muscle maximal force production and fatigue resistance in response to ML were both reduced in MDX mice as compared to healthy mice. MDX muscle also exhibited decreased cellular and molecular muscle remodeling (hypertrophy and promotion of slower/oxidative fiber type) in response to ML, and altered intracellular signalings involved in muscle growth and maintenance (mTOR, myostatin, follistatin, AMPK alpha 1, REDD1, atrogin-1, Bnip3). Moreover, dystrophin rescue via exon skipping restored the adaptive response to ML. Therefore our results demonstrate that the adaptive response in response to ML is impaired in dystrophic MDX muscle, most likely because of the dystrophin crucial role.
AB - Dystrophin contributes to force transmission and has a protein-scaffolding role for a variety of signaling complexes in skeletal muscle. In the present study, we tested the hypothesis that the muscle adaptive response following mechanical overloading (ML) would be decreased in MDX dystrophic muscle lacking dystrophin. We found that the gains in muscle maximal force production and fatigue resistance in response to ML were both reduced in MDX mice as compared to healthy mice. MDX muscle also exhibited decreased cellular and molecular muscle remodeling (hypertrophy and promotion of slower/oxidative fiber type) in response to ML, and altered intracellular signalings involved in muscle growth and maintenance (mTOR, myostatin, follistatin, AMPK alpha 1, REDD1, atrogin-1, Bnip3). Moreover, dystrophin rescue via exon skipping restored the adaptive response to ML. Therefore our results demonstrate that the adaptive response in response to ML is impaired in dystrophic MDX muscle, most likely because of the dystrophin crucial role.
U2 - 10.1371/journal.pone.0035346
DO - 10.1371/journal.pone.0035346
M3 - Article
C2 - 22511986
SN - 1932-6203
VL - 7
SP - -
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e35346
ER -