Hypertrophy and atrophy inversely regulate Caveolin-3 expression in myoblasts.
Caveolin-3 (Cav-3) is a muscle-specific membrane protein crucial for myoblast differentiation, as loss of the protein due to mutations within the gene causes an autosomal dominant form of limb girdle muscular dystrophy 1-c. Here we show that along with p38 activity the PI3-kinase/AKT/mTOR pathway is required for proper Cav-3 up-regulation during muscle differentiation and hypertrophy, as confirmed by the marked increase of Cav-3 expression in hypertrophied C2C12 cells transfected with an activated form of AKT. Accordingly, Cav-3 expression was further increased during hypertrophy of L6C5 myoblasts treated with Arg(8)-vasopressin and in hypertrophic muscles of MLC/mIGF-1 transgenic mice. In contrast, Cav-3 expression was down-regulated in C2C12 myotubes exposed to atrophic stimuli such as starvation or treatment with dexamethasone. This study clearly suggests that Cav-3 expression is causally linked to the maturation of muscle phenotype and it is tightly regulated by hypertrophic and atrophic stimuli.
Fanzani
Alessandro
A
Department of Biomedical Sciences and Biotechnology, Unit of Biochemistry, University of Brescia, Italy. fanzani@med.unibs.it
Musarò
Antonio
A
Stoppani
Elena
E
Giuliani
Roberta
R
Colombo
Francesca
F
Preti
Augusto
A
Marchesini
Sergio
S
D000818:Animals; D051244:Caveolin 3 / Q000378:metabolism*; D002460:Cell Line; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology*; D032446:Myoblasts / Q000378:metabolism* / Q000473:pathology*; D013223:Statistics as Topic
D051244:Caveolin 3