PMID- 16365054
OWN - NLM
STAT- MEDLINE
DCOM- 20060223
LR  - 20230216
IS  - 0022-3166 (Print)
IS  - 1541-6100 (Electronic)
IS  - 0022-3166 (Linking)
VI  - 136
IP  - 1
DP  - 2006 Jan
TI  - Rapamycin inhibits liver growth during refeeding in rats via control of ribosomal 
      protein translation but not cap-dependent translation initiation.
PG  - 27-33
AB  - We examined the role of the mammalian target of rapamycin (mTOR) in hepatic cell 
      growth. To dissociate cell growth from cell proliferation, we employed an in vivo 
      model of nonproliferative liver growth in rats, refeeding after 48 h of food 
      deprivation. Starvation resulted in a decrease in liver mass, liver protein, and 
      cell size, all of which were largely restored after 24 h of refeeding. 
      Administration of the mTOR inhibitor, rapamycin, before the refeeding period 
      partially inhibited the restoration of liver protein content. Refeeding was also 
      associated with an increase in ribosomal protein S6 phosphorylation and 
      phosphorylation of the eukaryotic initiation factor (eIF) 4E binding protein 1 
      (4E-BP1). 4E-BP1 phosphorylation was accompanied by a decrease in the abundance 
      of the complex containing 4E-BP1 with eIF4E. These changes were prevented by 
      rapamycin administration. However, association of eIF4E and eIF4G and eIF2alpha 
      phosphorylation, both of which are stimulated by refeeding, were insensitive to 
      rapamycin. The functional importance of these observations was confirmed by 
      polysome fractionation, which showed that translation initiation of 5' 
      oligopyrimidine tract-containing mRNAs, which encode ribosomal proteins, was 
      inhibited by rapamycin, whereas translation of signal transducer and activator of 
      transcription 1 (STAT1), a cap-dependent mRNA, was unaffected. The abundance of 
      ribosomal proteins paralleled total protein content during refeeding in both 
      control and rapamycin-injected rats. We conclude that accretion of liver protein 
      during refeeding is dependent on mTOR-mediated activation of the translation of 
      ribosomal proteins but not dependent on mTOR-mediated activation of cap-dependent 
      translation initiation.
FAU - Anand, Padmanabhan
AU  - Anand P
AD  - Department of Pediatrics, Brown University and Rhode Island Hospital, Providence, 
      RI 02903, USA.
FAU - Gruppuso, Philip A
AU  - Gruppuso PA
LA  - eng
GR  - R01 HD024455/HD/NICHD NIH HHS/United States
GR  - R01 HD035831/HD/NICHD NIH HHS/United States
GR  - HD24455/HD/NICHD NIH HHS/United States
GR  - HD35831/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Ribosomal Protein S6)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Eating
MH  - Eukaryotic Initiation Factor-2/drug effects/metabolism
MH  - Food Deprivation
MH  - Immunosuppressive Agents/*pharmacology
MH  - Liver/*drug effects/growth & development
MH  - Male
MH  - Phosphorylation
MH  - Protein Kinases/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6/*drug effects/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
PMC - PMC1386153
MID - NIHMS6201
EDAT- 2005/12/21 09:00
MHDA- 2006/02/24 09:00
PMCR- 2008/01/26
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/02/24 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
PHST- 2008/01/26 00:00 [pmc-release]
AID - S0022-3166(22)08005-1 [pii]
AID - 10.1093/jn/136.1.27 [doi]
PST - ppublish
SO  - J Nutr. 2006 Jan;136(1):27-33. doi: 10.1093/jn/136.1.27.