Calpain-dependent regulation of the skeletal muscle atrophy following unloadingстатья
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Дата последнего поиска статьи во внешних источниках: 26 января 2016 г.
Аннотация:Unloading causes rapid skeletal muscle atrophy due to increased protein degradation via activation of
calpains and decreased protein synthesis. Our study elucidated role of calpain-1 in the regulation of
ubiquitin proteasome pathway (UPP) and anabolic processes mediated by Akt-mTOR-p70S6K and MAPKErk
(p90RSK) signaling.We hypothesized that blocking calpain will inhibit activation of UPP and decrease
protein degradation resulting in reduction of unloading-induced skeletal muscle atrophy. Rats were
divided into three groups: non-treated control (C), three day hindlimb suspension with (HSPD) or
without (HS) treatment with calpain inhibitor PD150606. When compared with control PD150606
treatment during unloading: 1) attenuated loss of muscle mass, 2) prevented accumulation of calpain-1
(1.8-fold in HS vs 1.3-fold in HSPD) and ubiquitin (2.3-fold in HS vs 0.7-fold in HSPD) mRNA and ubiquitinated
proteins (1.6-fold in HS vs 0.8-fold in HSPD), 3) prevented decrease in the pAkt (0.4-fold in HS
vs 1-fold in HSPD) and pFOXO3 (0.2-fold in HS vs 1.2-fold in HSPD) levels, 4) prevented increase in
MAFbx (3.8-fold in HS vs 1.3-fold in HSPD) and eEF2k (1.8-fold in HS vs 0.6-fold in HSPD) mRNA. Our
study indicates that blocking of calpain during unloading decreases skeletal muscle atrophy by inhibiting
UPP activation and preserving anabolic signaling.