PMID- 16873412
OWN - NLM
STAT- MEDLINE
DCOM- 20061128
LR  - 20220410
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 576
IP  - Pt 2
DP  - 2006 Oct 15
TI  - Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation 
      and protein synthesis in human skeletal muscle.
PG  - 613-24
AB  - Resistance exercise is a potent stimulator of muscle protein synthesis and muscle 
      cell growth, with the increase in protein synthesis being detected within 2-3 h 
      post-exercise and remaining elevated for up to 48 h. However, during exercise, 
      muscle protein synthesis is inhibited. An increase in AMP-activated protein 
      kinase (AMPK) activity has recently been shown to decrease mammalian target of 
      rapamycin (mTOR) signalling to key regulators of translation initiation. We 
      hypothesized that the cellular mechanism for the inhibition of muscle protein 
      synthesis during an acute bout of resistance exercise in humans would be 
      associated with an activation of AMPK and an inhibition of downstream components 
      of the mTOR pathway (4E-BP1 and S6K1). We studied 11 subjects (seven men, four 
      women) before, during, and for 2 h following a bout of resistance exercise. 
      Muscle biopsy specimens were collected at each time point from the vastus 
      lateralis. We utilized immunoprecipitation and immunoblotting methods to measure 
      muscle AMPKalpha2 activity, and mTOR-associated upstream and downstream 
      signalling proteins, and stable isotope techniques to measure muscle fractional 
      protein synthetic rate (FSR). AMPKalpha2 activity (pmol min(-1) (mg protein)(-1)) 
      at baseline was 1.7 +/- 0.3, increased immediately post-exercise (3.0 +/- 0.6), 
      and remained elevated at 1 h post-exercise (P < 0.05). Muscle FSR decreased 
      during exercise and was significantly increased at 1 and 2 h post-exercise (P < 
      0.05). Phosphorylation of 4E-BP1 at Thr37/46 was significantly reduced 
      immediately post-exercise (P < 0.05). We conclude that AMPK activation and a 
      reduced phosphorylation of 4E-BP1 may contribute to the inhibition of muscle 
      protein synthesis during resistance exercise. However, by 1-2 h post-exercise, 
      muscle protein synthesis increased in association with an activation of protein 
      kinase B, mTOR, S6K1 and eEF2.
FAU - Dreyer, Hans C
AU  - Dreyer HC
AD  - University of Texas Medical Branch, Department of Physical Therapy, Division of 
      Rehabilitation Sciences, 301 University Blvd, Galveston, TX 77555-1144, USA.
FAU - Fujita, Satoshi
AU  - Fujita S
FAU - Cadenas, Jerson G
AU  - Cadenas JG
FAU - Chinkes, David L
AU  - Chinkes DL
FAU - Volpi, Elena
AU  - Volpi E
FAU - Rasmussen, Blake B
AU  - Rasmussen BB
LA  - eng
GR  - S10 RR16650/RR/NCRR NIH HHS/United States
GR  - R01AR049877/AR/NIAMS NIH HHS/United States
GR  - M01 RR00073/RR/NCRR NIH HHS/United States
GR  - R01 AR049877/AR/NIAMS NIH HHS/United States
GR  - M01 RR000073/RR/NCRR NIH HHS/United States
GR  - P30 AG024832/AG/NIA 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 - 20060727
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amino Acids)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Lactates)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Muscle Proteins)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Adult
MH  - Amino Acids/metabolism
MH  - Biopsy
MH  - Cell Cycle Proteins
MH  - Exercise/*physiology
MH  - Female
MH  - Glucose/pharmacokinetics
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Lactates/metabolism
MH  - Male
MH  - Multienzyme Complexes/genetics/*metabolism
MH  - Muscle Proteins/*metabolism
MH  - Muscle, Skeletal/blood supply/*metabolism/pathology
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Regional Blood Flow/physiology
MH  - TOR Serine-Threonine Kinases
MH  - Weight Lifting/physiology
PMC - PMC1890364
EDAT- 2006/07/29 09:00
MHDA- 2006/12/09 09:00
PMCR- 2007/10/15
CRDT- 2006/07/29 09:00
PHST- 2006/07/29 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/07/29 09:00 [entrez]
PHST- 2007/10/15 00:00 [pmc-release]
AID - jphysiol.2006.113175 [pii]
AID - 10.1113/jphysiol.2006.113175 [doi]
PST - ppublish
SO  - J Physiol. 2006 Oct 15;576(Pt 2):613-24. doi: 10.1113/jphysiol.2006.113175. Epub 
      2006 Jul 27.