PMID- 15591312
OWN - NLM
STAT- MEDLINE
DCOM- 20050407
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 9
DP  - 2005 Mar 4
TI  - Resistance exercise increases muscle protein synthesis and translation of 
      eukaryotic initiation factor 2Bepsilon mRNA in a mammalian target of 
      rapamycin-dependent manner.
PG  - 7570-80
AB  - The contribution of mammalian target of rapamycin (mTOR) signaling to the 
      resistance exercise-induced stimulation of skeletal muscle protein synthesis was 
      assessed by administering rapamycin to Sprague-Dawley rats 2 h prior to a bout of 
      resistance exercise. Animals were sacrificed 16 h postexercise, and gastrocnemius 
      protein synthesis, mTOR signaling, and biomarkers of translation initiation were 
      assessed. Exercise stimulated the rate of protein synthesis; however, this effect 
      was prevented by pretreatment with rapamycin. The stimulation of protein 
      synthesis was mediated by an increase in translation initiation, since exercise 
      caused an increase in polysome aggregation that was abrogated by rapamycin 
      administration. Taken together, the data suggest that the effect of rapamycin was 
      not mediated by reduced phosphorylation of eukaryotic initiation factor 4E 
      (eIF4E) binding protein 1 (BP1), because exercise did not cause a significant 
      change in 4E-BP1(Thr-70) phosphorylation, 4E-BP1-eIF4E association, or eIF4F 
      complex assembly concomitant with increased protein synthetic rates. 
      Alternatively, there was a rapamycin-sensitive decrease in relative 
      eIF2Bepsilon(Ser-535) phosphorylation that was explained by a significant 
      increase in the expression of eIF2Bepsilon protein. The proportion of 
      eIF2Bepsilon mRNA in polysomes was increased following exercise, an effect that 
      was prevented by rapamycin treatment, suggesting that the increase in 
      eIF2Bepsilon protein expression was mediated by an mTOR-dependent increase in 
      translation of the mRNA encoding the protein. The increase in eIF2Bepsilon mRNA 
      translation and protein abundance occurred independent of similar changes in 
      other eIF2B subunits. These data suggest a novel link between mTOR signaling and 
      eIF2Bepsilon mRNA translation that could contribute to the stimulation of protein 
      synthesis following acute resistance exercise.
FAU - Kubica, Neil
AU  - Kubica N
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State University 
      College of Medicine, Hershey, Pennsylvania 17033, USA.
FAU - Bolster, Douglas R
AU  - Bolster DR
FAU - Farrell, Peter A
AU  - Farrell PA
FAU - Kimball, Scot R
AU  - Kimball SR
FAU - Jefferson, Leonard S
AU  - Jefferson LS
LA  - eng
GR  - DK15658/DK/NIDDK NIH HHS/United States
GR  - GM08619/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041210
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Eukaryotic Initiation Factor-2B)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Ribosomal)
RN  - 0 (Ribosomal Protein S6)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Carrier Proteins/metabolism
MH  - Eukaryotic Initiation Factor-2B/metabolism/*physiology
MH  - Eukaryotic Initiation Factors/metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Muscle, Skeletal/*metabolism/pathology
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Physical Conditioning, Animal
MH  - Polyribosomes/chemistry
MH  - *Protein Biosynthesis
MH  - Protein Kinases/*metabolism
MH  - RNA, Messenger/metabolism
MH  - RNA, Ribosomal/chemistry
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribosomal Protein S6/chemistry
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Time Factors
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2004/12/14 09:00
MHDA- 2005/04/09 09:00
CRDT- 2004/12/14 09:00
PHST- 2004/12/14 09:00 [pubmed]
PHST- 2005/04/09 09:00 [medline]
PHST- 2004/12/14 09:00 [entrez]
AID - S0021-9258(19)30520-4 [pii]
AID - 10.1074/jbc.M413732200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Mar 4;280(9):7570-80. doi: 10.1074/jbc.M413732200. Epub 2004 
      Dec 10.