PMID- 18801898
OWN - NLM
STAT- MEDLINE
DCOM- 20090312
LR  - 20211203
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 150
IP  - 1
DP  - 2009 Jan
TI  - Down-regulation of Akt/mammalian target of rapamycin signaling pathway in 
      response to myostatin overexpression in skeletal muscle.
PG  - 286-94
LID - 10.1210/en.2008-0959 [doi]
AB  - Myostatin, a member of the TGF-beta family, has been identified as a master 
      regulator of embryonic myogenesis and early postnatal skeletal muscle growth. 
      However, cumulative evidence also suggests that alterations in skeletal muscle 
      mass are associated with dysregulation in myostatin expression and that myostatin 
      may contribute to muscle mass loss in adulthood. Two major branches of the Akt 
      pathway are relevant for the regulation of skeletal muscle mass, the 
      Akt/mammalian target of rapamycin (mTOR) pathway, which controls protein 
      synthesis, and the Akt/forkhead box O (FOXO) pathway, which controls protein 
      degradation. Here, we provide further insights into the mechanisms by which 
      myostatin regulates skeletal muscle mass by showing that myostatin negatively 
      regulates Akt/mTOR signaling pathway. Electrotransfer of a myostatin expression 
      vector into the tibialis anterior muscle of Sprague Dawley male rats increased 
      myostatin protein level and decreased skeletal muscle mass 7 d after gene 
      electrotransfer. Using RT-PCR and immunoblot analyses, we showed that myostatin 
      overexpression was ineffective to alter the ubiquitin-proteasome pathway. By 
      contrast, myostatin acted as a negative regulator of Akt/mTOR pathway. This was 
      supported by data showing that the phosphorylation of Akt on Thr308, tuberous 
      sclerosis complex 2 on Thr1462, ribosomal protein S6 on Ser235/236, and 4E-BP1 on 
      Thr37/46 was attenuated 7 d after myostatin gene electrotransfer. The data 
      support the conclusion that Akt/mTOR signaling is a key target that accounts for 
      myostatin function during muscle atrophy, uncovering a novel role for myostatin 
      in protein metabolism and more specifically in the regulation of translation in 
      skeletal muscle.
FAU - Amirouche, Adel
AU  - Amirouche A
AD  - Pole de Recherche et d'Enseignement Superieur Universite de Lyon, Universite Jean 
      Monnet, Laboratoire de Physiologie de l'Exercice, Equipe d'accueil, Saint 
      Etienne, France.
FAU - Durieux, Anne-Cecile
AU  - Durieux AC
FAU - Banzet, Sebastien
AU  - Banzet S
FAU - Koulmann, Nathalie
AU  - Koulmann N
FAU - Bonnefoy, Regis
AU  - Bonnefoy R
FAU - Mouret, Catherine
AU  - Mouret C
FAU - Bigard, Xavier
AU  - Bigard X
FAU - Peinnequin, Andre
AU  - Peinnequin A
FAU - Freyssenet, Damien
AU  - Freyssenet D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080918
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (DNA Primers)
RN  - 0 (Myostatin)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Atrophy
MH  - DNA/genetics
MH  - DNA Primers
MH  - Down-Regulation
MH  - Male
MH  - Muscle, Skeletal/pathology/*physiology
MH  - Myostatin/*genetics
MH  - Plasmids/genetics
MH  - Protein Biosynthesis
MH  - Protein Kinases/*genetics
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TOR Serine-Threonine Kinases
EDAT- 2008/09/20 09:00
MHDA- 2009/03/13 09:00
CRDT- 2008/09/20 09:00
PHST- 2008/09/20 09:00 [pubmed]
PHST- 2009/03/13 09:00 [medline]
PHST- 2008/09/20 09:00 [entrez]
AID - en.2008-0959 [pii]
AID - 10.1210/en.2008-0959 [doi]
PST - ppublish
SO  - Endocrinology. 2009 Jan;150(1):286-94. doi: 10.1210/en.2008-0959. Epub 2008 Sep 
      18.