PMID- 29757673
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
DP  - 2018 May 14
TI  - Rapamycin-insensitive mechanistic target of rapamycin regulates basal and 
      resistance exercise-induced muscle protein synthesis.
PG  - fj201701422R
LID - 10.1096/fj.201701422R [doi]
AB  - We investigated whether rapamycin-insensitive mechanistic target of rapamycin 
      (mTOR) signaling plays a role in regulating resistance exercise-induced muscle 
      protein synthesis. We used a rodent model of resistance exercise and compared the 
      effect of rapamycin, an allosteric mTOR inhibitor, with the effect of AZD8055, an 
      ATP-competitive mTOR kinase inhibitor. The right gastrocnemius muscle of male 
      Sprague-Dawley rats age 11 wk was contracted isometrically via percutaneous 
      electrical stimulation (100 Hz, 5 sets of ten 3-s contractions, 7 s of rest 
      between contractions, 3 min of rest between sets), and the left gastrocnemius 
      muscle served as control. Vehicle, rapamycin, or AZD8055 were intraperitoneally 
      injected 1 h before resistance exercise. Results indicated that both rapamycin 
      and AZD8055 inhibited mTOR complex 1 (mTORC1)/70-kDa ribosomal protein S6 kinase 
      signaling similarly, whereas mTORC1/eukaryotic translation initiation factor 
      4E-binding protein 1 signaling was greatly inhibited by AZD8055. Moreover, only 
      AZD8055 inhibited the phosphorylation of Akt at Ser473, a downstream target of 
      mTORC2. AZD8055, but not rapamycin, completely inhibited the resistance 
      exercise-induced increase in muscle protein synthesis. We conclude that the 
      resistance exercise-induced increase in muscle protein synthesis is an mTOR 
      signaling-dependent process. Furthermore, both rapamycin-sensitive and 
      -insensitive mTOR signaling regulate this event.-Ogasawara, R., Suginohara, T. 
      Rapamycin-insensitive mechanistic target of rapamycin regulates basal and 
      resistance exercise-induced muscle protein synthesis.
FAU - Ogasawara, Riki
AU  - Ogasawara R
AD  - Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, 
      Nagoya, Japan.
FAU - Suginohara, Takeshi
AU  - Suginohara T
AD  - Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, 
      Nagoya, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180514
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
OTO - NOTNLM
OT  - AZD8055
OT  - contraction
OT  - metabolism
OT  - skeletal muscle
OT  - translation
EDAT- 2018/05/15 06:00
MHDA- 2018/05/15 06:00
CRDT- 2018/05/15 06:00
PHST- 2018/05/15 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2018/05/15 06:00 [entrez]
AID - 10.1096/fj.201701422R [doi]
PST - aheadofprint
SO  - FASEB J. 2018 May 14:fj201701422R. doi: 10.1096/fj.201701422R.