PMID- 28856713
OWN - NLM
STAT- MEDLINE
DCOM- 20181015
LR  - 20211204
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 119
IP  - 2
DP  - 2018 Feb
TI  - Leucine supplementation after mechanical stimulation activates protein synthesis 
      via L-type amino acid transporter 1 in vitro.
PG  - 2094-2101
LID - 10.1002/jcb.26371 [doi]
AB  - Branched-chain amino acid supplements consumed following exercise are widely used 
      to increase muscle mass. Although both exercise (ie, mechanical stimulation) and 
      branched-chain amino acid leucine supplementation have been reported to stimulate 
      muscle protein synthesis by activating the mammalian target of rapamycin (mTOR) 
      signaling pathway independently, the mechanisms underlying their synergistic 
      effects are largely unknown. Utilizing cultured differentiated C2C12 myotubes, we 
      established a combination treatment model in which the cells were subjected to 
      cyclic uniaxial mechanical stretching (4 h, 15%, 1 Hz) followed by stimulation 
      with 2 mM leucine for 45 min. Phosphorylation of p70 S6 kinase (p70S6K), an 
      mTOR-regulated marker of protein translation initiation, was significantly 
      increased following mechanical stretching alone but returned to the baseline 
      after 4 h. Leucine supplementation further increased p70S6K phosphorylation, with 
      a greater increase observed in the stretched cells than in the non-stretched 
      cells. Notably, the expression of L-type amino acid transporter 1 (LAT1), a 
      stimulator of the mTOR pathway, was also increased by mechanical stretching, and 
      siRNA-mediated knockdown partially attenuated leucine-induced p70S6K 
      phosphorylation. These results suggest that mechanical stretching promotes LAT1 
      expression and, consequently, amino acid uptake, leading to enhanced 
      leucine-induced activation of protein synthesis. LAT1 has been demonstrated to be 
      a point of crosstalk between exercise- and nutrition-induced skeletal muscle 
      growth.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Nakai, Naoya
AU  - Nakai N
AUID- ORCID: 0000-0003-4227-2576
AD  - Department of Nutrition, University of Shiga Prefecture, Hikone, Shiga, Japan.
FAU - Kawano, Fuminori
AU  - Kawano F
AD  - Graduate School of Health Sciences, Matsumoto University, Matsumoto, Nagano, 
      Japan.
FAU - Murakami, Taro
AU  - Murakami T
AD  - Department of Nutrition, Shigakkan University, Ohbu, Aichi, Japan.
FAU - Nakata, Ken
AU  - Nakata K
AD  - Medicine for Sports and Performing Arts, Graduate School of Medicine, Osaka 
      University, Toyonaka, Osaka, Japan.
FAU - Higashida, Kazuhiko
AU  - Higashida K
AD  - Department of Nutrition, University of Shiga Prefecture, Hikone, Shiga, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170918
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Amino Acid Transport System y+)
RN  - 0 (Amino Acid Transport System y+L)
RN  - 0 (Slc7a7 protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Amino Acid Transport System y+/*metabolism
MH  - Amino Acid Transport System y+L
MH  - Animals
MH  - Gene Expression Regulation/drug effects
MH  - In Vitro Techniques
MH  - Leucine/*pharmacology
MH  - Mice
MH  - Muscle Fibers, Skeletal/*cytology/drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Biosynthesis/*drug effects
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Stress, Mechanical
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - *Up-Regulation
OTO - NOTNLM
OT  - leucine
OT  - mechanical stimuli
OT  - mtor
OT  - p70 S6 kinase
OT  - protein synthesis
EDAT- 2017/09/01 06:00
MHDA- 2018/10/16 06:00
CRDT- 2017/09/01 06:00
PHST- 2017/06/27 00:00 [received]
PHST- 2017/08/23 00:00 [accepted]
PHST- 2017/09/01 06:00 [pubmed]
PHST- 2018/10/16 06:00 [medline]
PHST- 2017/09/01 06:00 [entrez]
AID - 10.1002/jcb.26371 [doi]
PST - ppublish
SO  - J Cell Biochem. 2018 Feb;119(2):2094-2101. doi: 10.1002/jcb.26371. Epub 2017 Sep 
      18.