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 journalArticlepeer-review

30 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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