PMID- 18682538
OWN - NLM
STAT- MEDLINE
DCOM- 20081117
LR  - 20220408
IS  - 0193-1849 (Print)
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 295
IP  - 4
DP  - 2008 Oct
TI  - Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by 
      enhancing mTORC1 activation.
PG  - E868-75
LID - 10.1152/ajpendo.90314.2008 [doi]
AB  - Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced 
      sensitivity to the postprandial rise in amino acids, particularly leucine. To 
      elucidate the molecular mechanism by which leucine stimulates protein synthesis 
      in neonatal muscle, overnight-fasted 7-day-old piglets were treated with 
      rapamycin [an inhibitor of mammalian target of rapamycin (mTOR) complex (mTORC)1] 
      for 1 h and then infused with leucine for 1 h. Fractional rates of protein 
      synthesis and activation of signaling components that lead to mRNA translation 
      were determined in skeletal muscle. Rapamycin completely blocked leucine-induced 
      muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an 
      indicator of mTORC1 activation. Rapamycin blocked the leucine-induced 
      phosphorylation of mTOR, S6 kinase 1 (S6K1), and eukaryotic initiation factor 
      (eIF)4E-binding protein-1 (4E-BP1) and formation of the eIF4E.eIF4G complex and 
      increased eIF4E.4E-BP1 complex abundance. Rapamycin had no effect on the 
      association of mTOR with rictor, a crucial component for mTORC2 activation, or G 
      protein beta-subunit-like protein (GbetaL), a component of mTORC1 and mTORC2. 
      Neither leucine nor rapamycin affected the phosphorylation of AMP-activated 
      protein kinase (AMPK), PKB, or tuberous sclerosis complex (TSC)2, signaling 
      components that reside upstream of mTOR. Eukaryotic elongation factor (eEF)2 
      phosphorylation was not affected by leucine or rapamycin, although current dogma 
      indicates that eEF2 phosphorylation is mTOR dependent. Together, these in vivo 
      data suggest that leucine stimulates muscle protein synthesis in neonates by 
      enhancing mTORC1 activation and its downstream effectors.
FAU - Suryawan, Agus
AU  - Suryawan A
AD  - United States Department of Agriculture/Agriculture Research Service Children's 
      Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 
      Houston, Texas 77030, USA.
FAU - Jeyapalan, Asumthia S
AU  - Jeyapalan AS
FAU - Orellana, Renan A
AU  - Orellana RA
FAU - Wilson, Fiona A
AU  - Wilson FA
FAU - Nguyen, Hanh V
AU  - Nguyen HV
FAU - Davis, Teresa A
AU  - Davis TA
LA  - eng
GR  - R01 AR044474-13/AR/NIAMS NIH HHS/United States
GR  - R01 AR044474-11/AR/NIAMS NIH HHS/United States
GR  - AR-44474/AR/NIAMS NIH HHS/United States
GR  - R01 AR044474-12/AR/NIAMS NIH HHS/United States
GR  - R01 AR044474/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080805
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Muscle Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - GMW67QNF9C (Leucine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Animals
MH  - Animals, Newborn/*physiology
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Blotting, Western
MH  - Eukaryotic Initiation Factor-4E/biosynthesis/genetics
MH  - Kinetics
MH  - Leucine/*pharmacology
MH  - Multienzyme Complexes/metabolism
MH  - Muscle Proteins/*biosynthesis
MH  - Muscle, Skeletal/*drug effects/*metabolism
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/biosynthesis
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - Swine
MH  - TOR Serine-Threonine Kinases
PMC - PMC2575905
EDAT- 2008/08/07 09:00
MHDA- 2008/11/18 09:00
PMCR- 2009/10/01
CRDT- 2008/08/07 09:00
PHST- 2008/08/07 09:00 [pubmed]
PHST- 2008/11/18 09:00 [medline]
PHST- 2008/08/07 09:00 [entrez]
PHST- 2009/10/01 00:00 [pmc-release]
AID - 90314.2008 [pii]
AID - E-90314-2008 [pii]
AID - 10.1152/ajpendo.90314.2008 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E868-75. doi: 
      10.1152/ajpendo.90314.2008. Epub 2008 Aug 5.