PMID- 11997383
OWN - NLM
STAT- MEDLINE
DCOM- 20020827
LR  - 20220228
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 27
DP  - 2002 Jul 5
TI  - AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle 
      through down-regulated mammalian target of rapamycin (mTOR) signaling.
PG  - 23977-80
AB  - AMP-activated protein kinase (AMPK) is viewed as an energy sensor that acts to 
      modulate glucose uptake and fatty acid oxidation in skeletal muscle. Given that 
      protein synthesis is a high energy-consuming process, it may be transiently 
      depressed during cellular energy stress. Thus, the intent of this investigation 
      was to examine whether AMPK activation modulates the translational control of 
      protein synthesis in skeletal muscle. Injections of 
      5-aminoimidazole-4-carboxamide 1-beta-d-ribonucleoside (AICAR) were used to 
      activate AMPK in male rats. The activity of alpha1 AMPK remained unchanged in 
      gastrocnemius muscle from AICAR-treated animals compared with controls, whereas 
      alpha2 AMPK activity was significantly increased (51%). AICAR treatment resulted 
      in a reduction in protein synthesis to 45% of the control value. This depression 
      was associated with decreased activation of protein kinases in the mammalian 
      target of rapamycin (mTOR) signal transduction pathway as evidenced by reduced 
      phosphorylation of protein kinase B on Ser(473), mTOR on Ser(2448), ribosomal 
      protein S6 kinase on Thr(389), and eukaryotic initiation factor eIF4E-binding 
      protein on Thr(37). A reduction in eIF4E associated with eIF4G to 10% of the 
      control value was also noted. In contrast, eIF2B activity remained unchanged in 
      response to AICAR treatment and therefore would not appear to contribute to the 
      depression in protein synthesis. This is the first investigation to demonstrate 
      changes in translation initiation and skeletal muscle protein synthesis in 
      response to AMPK activation.
FAU - Bolster, Douglas R
AU  - Bolster DR
AD  - Department of Cellular and Molecular Physiology, The Pennsylvania State 
      University College of Medicine, Hershey, Pennsylvania 17033, USA.
FAU - Crozier, Stephen J
AU  - Crozier SJ
FAU - Kimball, Scot R
AU  - Kimball SR
FAU - Jefferson, Leonard S
AU  - Jefferson LS
LA  - eng
GR  - DK15658/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020507
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Muscle Proteins)
RN  - 0 (Peptide Initiation Factors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Ribonucleotides)
RN  - 17885-08-4 (Phosphoserine)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
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  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/*pharmacology
MH  - Animals
MH  - Enzyme Activation
MH  - Eukaryotic Initiation Factor-4E
MH  - Male
MH  - Multienzyme Complexes/*metabolism
MH  - Muscle Proteins/antagonists & inhibitors/*biosynthesis
MH  - Muscle, Skeletal/drug effects/*enzymology
MH  - Peptide Initiation Factors/metabolism
MH  - Phosphoserine/metabolism
MH  - Protein Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Ribonucleotides/*pharmacology
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases
EDAT- 2002/05/09 10:00
MHDA- 2002/08/28 10:01
CRDT- 2002/05/09 10:00
PHST- 2002/05/09 10:00 [pubmed]
PHST- 2002/08/28 10:01 [medline]
PHST- 2002/05/09 10:00 [entrez]
AID - S0021-9258(19)66559-2 [pii]
AID - 10.1074/jbc.C200171200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Jul 5;277(27):23977-80. doi: 10.1074/jbc.C200171200. Epub 2002 
      May 7.