PMID- 15613684
OWN - NLM
STAT- MEDLINE
DCOM- 20050518
LR  - 20211203
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 288
IP  - 5
DP  - 2005 May
TI  - Repression of protein synthesis and mTOR signaling in rat liver mediated by the 
      AMPK activator aminoimidazole carboxamide ribonucleoside.
PG  - E980-8
AB  - The studies described herein were designed to investigate the effects of 
      5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), an activator of 
      the AMP-activated protein kinase (AMPK), on the translational control of protein 
      synthesis and signaling through the mammalian target of rapamycin (mTOR) in rat 
      liver. Effects of AICAR observed in vivo were compared with those obtained in an 
      in situ perfused liver preparation to investigate activation of AMPK in the 
      absence of accompanying changes in hormones and nutrients. AMPK became 
      hyperphosphorylated, as assessed by a gel-shift analysis, in response to AICAR 
      both in vivo and in situ; however, increased relative phosphorylation at the 
      Thr172 site on the kinase was observed only in perfused liver. Phosphorylation of 
      AMPK either in vivo or in situ was associated with a repression of protein 
      synthesis as well as decreased phosphorylation of a number of targets of mTOR 
      signaling including ribosomal protein S6 kinase 1, eukaryotic initiation factor 
      (eIF)4G, and eIF4E-binding protein (4E-BP)1. The phosphorylation changes in eIF4G 
      and 4E-BP1 were accompanied by a reduction in the amount of eIF4E present in the 
      active eIF4E.eIF4G complex and an increase in the amount present in the inactive 
      eIF4E.4E-BP1 complex. Reduced insulin signaling as well as differences in 
      nutrient availability may have contributed to the effects observed in vivo as 
      AICAR caused a fall in the serum insulin concentration. Overall, however, the 
      results from both experimental models support a scenario in which AICAR directly 
      represses protein synthesis and mTOR signaling in the liver through an 
      AMPK-dependent mechanism.
FAU - Reiter, Ali K
AU  - Reiter AK
AD  - Department of Cellular and Molecular Physiology, The Pennsylvania State 
      University College of Medicine, P.O. Box 850, Hershey, PA 17033, USA.
FAU - Bolster, Douglas R
AU  - Bolster DR
FAU - Crozier, Stephen J
AU  - Crozier SJ
FAU - Kimball, Scot R
AU  - Kimball SR
FAU - Jefferson, Leonard S
AU  - Jefferson LS
LA  - eng
GR  - DK-13499/DK/NIDDK NIH HHS/United States
GR  - GM-08619/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041221
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Ribonucleotides)
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 (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/*administration & dosage/*analogs & derivatives
MH  - Animals
MH  - Gene Expression Regulation, Enzymologic/drug effects/physiology
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Multienzyme Complexes/drug effects/*metabolism
MH  - Protein Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribonucleotides/*administration & dosage
MH  - Signal Transduction/drug effects/physiology
MH  - TOR Serine-Threonine Kinases
EDAT- 2004/12/23 09:00
MHDA- 2005/05/19 09:00
CRDT- 2004/12/23 09:00
PHST- 2004/12/23 09:00 [pubmed]
PHST- 2005/05/19 09:00 [medline]
PHST- 2004/12/23 09:00 [entrez]
AID - 00333.2004 [pii]
AID - 10.1152/ajpendo.00333.2004 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2005 May;288(5):E980-8. doi: 
      10.1152/ajpendo.00333.2004. Epub 2004 Dec 21.