PMID- 22300302
OWN - NLM
STAT- MEDLINE
DCOM- 20121217
LR  - 20131121
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 39
IP  - 4
DP  - 2012 Apr
TI  - Calpastatin overexpression in the skeletal muscle of mice prevents 
      clenbuterol-induced muscle hypertrophy and phenotypic shift.
PG  - 364-72
LID - 10.1111/j.1440-1681.2012.05677.x [doi]
AB  - Accumulating evidence suggests that the calpain/calpastatin system is involved in 
      skeletal muscle remodelling induced by beta(2) -adrenoceptor agonist treatment. In 
      addition to other pathways, the Akt/mammalian target of rapamycin (mTOR) pathway, 
      controlling protein synthesis, and the calcium/calmodulin-dependent protein 
      kinase 2 (CamK2) and AMP-activated protein kinase (AMPK) pathways, recently 
      identified as calpain substrates, could be relevant in beta(2) -adrenoceptor 
      agonist-induced skeletal muscle remodelling. In the present study we investigated 
      muscle hypertrophy and phenotypic shifts, as well as the molecular response of 
      components of the Akt/mTOR pathway (i.e. Akt, eukaryotic initiation factor 
      4E-binding protein 1 (4E-BP1), ribosomal protein S6 (rpS6), CamK2 and AMPK), in 
      response to calpastatin overexpression in the skeletal muscle of mice treated 
      with 1 mg/kg per day clenbuterol for 21 days. Using gene electrotransfer of a 
      calpastatin expression vector into the tibialis anterior of adult mice, we found 
      that calpastatin overexpression attenuates muscle hypertrophy and phenotypic 
      shifts induced by clenbuterol treatment. At the molecular level, calpastatin 
      overexpression markedly decreased calpain activity, but was ineffective in 
      altering the phosphorylation of Akt, 4E-BP1 and rpS6. In contrast, calpastatin 
      overexpression increased the protein expression of both total AMPK and total 
      CamK2. In conclusion, the results support the contention that the 
      calpain/calpastatin system plays a crucial role in skeletal muscle hypertrophy 
      and phenotypic shifts under chronic clenbuterol treatment, with AMPK and CamK2 
      probably playing a minor role. Moreover, the calpastatin-induced inhibition of 
      hypertrophy under clenbuterol treatment was not related to a decreased 
      mTOR-dependent initiation of protein translation.
CI  - (c) 2012 The Authors Clinical and Experimental Pharmacology and Physiology (c) 2012 
      Blackwell Publishing Asia Pty Ltd.
FAU - Douillard, Aymeric
AU  - Douillard A
AD  - National Institute for Agronomical Research (INRA), Muscular Dynamic and 
      Metabolism, University of Montpellier, Montpellier, France. aymerichpz@yahoo.fr
FAU - Galbes, Olivier
AU  - Galbes O
FAU - Begue, Gwenaelle
AU  - Begue G
FAU - Rossano, Bernadette
AU  - Rossano B
FAU - Levin, John
AU  - Levin J
FAU - Vernus, Barbara
AU  - Vernus B
FAU - Bonnieu, Anne
AU  - Bonnieu A
FAU - Candau, Robin
AU  - Candau R
FAU - Py, Guillaume
AU  - Py G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Calcium-Binding Proteins)
RN  - 79079-11-1 (calpastatin)
RN  - EC 3.4.22.- (Calpain)
RN  - XTZ6AXU7KN (Clenbuterol)
SB  - IM
MH  - Animals
MH  - Calcium-Binding Proteins/*biosynthesis/genetics
MH  - Calpain/*antagonists & inhibitors/metabolism
MH  - Cattle
MH  - Clenbuterol/antagonists & inhibitors/*toxicity
MH  - Gene Expression Regulation
MH  - Hypertrophy/chemically induced/metabolism/prevention & control
MH  - Male
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Muscle, Skeletal/drug effects/*metabolism/*pathology
MH  - *Phenotype
EDAT- 2012/02/04 06:00
MHDA- 2012/12/18 06:00
CRDT- 2012/02/04 06:00
PHST- 2012/02/04 06:00 [entrez]
PHST- 2012/02/04 06:00 [pubmed]
PHST- 2012/12/18 06:00 [medline]
AID - 10.1111/j.1440-1681.2012.05677.x [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2012 Apr;39(4):364-72. doi: 
      10.1111/j.1440-1681.2012.05677.x.