Calpain-dependent regulation of the skeletal muscle atrophy following unloading

Boris S. Shenkman, Svetlana P. Belova, Yulia N. Lomonosova, Tatiana Y. Kostrominova, Tatyana L. Nemirovskaya

Research output: Contribution to journalArticle

27 Scopus citations


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 MAPK-Erk (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.

Original languageEnglish (US)
Pages (from-to)36-41
Number of pages6
JournalArchives of Biochemistry and Biophysics
StatePublished - Oct 15 2015


  • Calpain
  • MAFbx
  • Skeletal muscle unloading
  • Ubiquitin proteasome pathway
  • pFOXO3

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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