PMID- 22539739
OWN - NLM
STAT- MEDLINE
DCOM- 20120905
LR  - 20211203
IS  - 1477-9145 (Electronic)
IS  - 0022-0949 (Linking)
VI  - 215
IP  - Pt 10
DP  - 2012 May 15
TI  - Regulation of the mTOR signaling network in hibernating thirteen-lined ground 
      squirrels.
PG  - 1720-7
LID - 10.1242/jeb.066225 [doi]
AB  - For many small mammals, survival over the winter months is a serious challenge 
      because of low environmental temperatures and limited food availability. The 
      solution for many species, such as thirteen-lined ground squirrels (Ictidomys 
      tridecemlineatus), is hibernation, an altered physiological state characterized 
      by seasonal heterothermy and entry into long periods of torpor that are 
      interspersed with short arousals back to euthermia. During torpor, metabolic rate 
      is strongly reduced to achieve major energy savings, and a coordinated depression 
      of non-essential ATP-expensive functions such as protein synthesis takes place. 
      This study examines the mammalian target of rapamycin (mTOR) signaling pathway, a 
      crucial component of the insulin receptor network, over six stages of the 
      torpor-arousal cycle of hibernation. Immunoblots showed that the phosphorylation 
      state of mTOR(Ser2448) was strongly reduced in skeletal muscle (by 55%) during 
      late torpor but increased by 200% during early arousal compared with euthermia. 
      However, the phosphorylation state of this residue remained relatively constant 
      in cardiac muscle during torpor but was enhanced during entrance into torpor and 
      early arousal from torpor stages (by 2.9- and 3.2-fold, respectively). 
      Phosphorylation states of upstream regulators of mTOR, p-Akt(Thr473) and 
      p-TSC2(Thr1462), were also suppressed in skeletal muscle by 55 and 51%, 
      respectively, during late torpor, as were selected downstream 
      substrates--p-4E-BP1(Thr46) and p-S6(Ser235) contents dropped by 74 and 41%, 
      respectively. Overall, the results indicate suppressed mTOR signaling in skeletal 
      muscle, but not cardiac muscle, during torpor. By contrast, activation of mTOR 
      and other components of the mTORC1 complex (p-PRAS40(Thr246) and GbetaL) occurred 
      during early arousal in both skeletal and cardiac muscle.
FAU - Wu, Cheng-Wei
AU  - Wu CW
AD  - Institute of Biochemistry and Department of Biology, Carleton University, 1125 
      Colonel By Drive, Ottawa, ON, Canada K1S 5B6.
FAU - Storey, Kenneth B
AU  - Storey KB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Exp Biol
JT  - The Journal of experimental biology
JID - 0243705
RN  - 0 (Eukaryotic Initiation Factors)
RN  - EC 2.7.1.1 (MTOR protein, human)
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  - Environment
MH  - Eukaryotic Initiation Factors/metabolism
MH  - *Hibernation
MH  - Models, Biological
MH  - Muscle, Skeletal/metabolism
MH  - Phosphorylation
MH  - Protein Biosynthesis
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Sciuridae
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Temperature
EDAT- 2012/04/28 06:00
MHDA- 2012/09/06 06:00
CRDT- 2012/04/28 06:00
PHST- 2012/04/28 06:00 [entrez]
PHST- 2012/04/28 06:00 [pubmed]
PHST- 2012/09/06 06:00 [medline]
AID - 215/10/1720 [pii]
AID - 10.1242/jeb.066225 [doi]
PST - ppublish
SO  - J Exp Biol. 2012 May 15;215(Pt 10):1720-7. doi: 10.1242/jeb.066225.