PMID- 17291499
OWN - NLM
STAT- MEDLINE
DCOM- 20070626
LR  - 20201209
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 204
IP  - 2
DP  - 2007 Apr
TI  - Chronic alcohol consumption alters mammalian target of rapamycin (mTOR), reduces 
      ribosomal p70s6 kinase and p4E-BP1 levels in mouse cerebral cortex.
PG  - 840-4
AB  - Reduced insulin sensitivity following chronic alcohol consumption may contribute 
      to alcohol-induced brain damage although the underlying mechanism(s) has not been 
      elucidated. This study was designed to examine the effect of chronic alcohol 
      intake on insulin signaling in mouse cerebral cortex. FVB mice were fed with a 4% 
      alcohol diet for 16 weeks. Insulin receptor substrates (IRS-1, IRS-2) and 
      post-receptor signaling molecules Akt, mammalian target of rapamycin (mTOR), 
      ribosomal p70s6 kinase (p70s6k) and the eukaryotic translation initiation factor 
      4E (eIF4E)-binding protein 1 (4E-BP1) as well as the apoptotic marker caspase-3 
      were evaluated using Western blot analysis. Chronic alcohol intake significantly 
      dampened whole body glucose tolerance, enhanced expression of caspase-3 and mTOR, 
      reduced p70s6k and 4E-BP1 with little effect on Akt signaling in 
      alcohol-consuming mice. These data suggest that chronic alcohol intake may 
      contribute to cerebral cortex dysfunction through mechanisms related, at least in 
      part, to dampened post insulin receptor signaling at the levels of mTOR, p70s6k 
      and 4E-BP1.
FAU - Li, Qun
AU  - Li Q
AD  - Division of Pharmaceutical Sciences, Center for Cardiovascular Research and 
      Alternative Medicine and Graduate Neuroscience Program, University of Wyoming, 
      Laramie, WY 82071, USA.
FAU - Ren, Jun
AU  - Ren J
LA  - eng
GR  - R01 AA013412/AA/NIAAA NIH HHS/United States
GR  - R15 AA013575/AA/NIAAA NIH HHS/United States
GR  - 1R01 AA 013412-01A2/AA/NIAAA NIH HHS/United States
GR  - 1R15 AA/HL 13575-01/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070113
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Alcohols)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Eif4ebp1 protein, mouse)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 3.4.22.- (Caspase 3)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Alcohol Drinking/*metabolism
MH  - Alcohols/administration & dosage
MH  - Analysis of Variance
MH  - Animals
MH  - Carrier Proteins/*metabolism
MH  - Caspase 3/metabolism
MH  - Cell Cycle Proteins
MH  - Cerebral Cortex/drug effects/*metabolism
MH  - Eukaryotic Initiation Factors
MH  - Glucose Tolerance Test/methods
MH  - Male
MH  - Mice
MH  - Phosphoproteins/*metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - Sirolimus/*metabolism
PMC - PMC1895598
MID - NIHMS21543
EDAT- 2007/02/13 09:00
MHDA- 2007/06/27 09:00
PMCR- 2008/04/01
CRDT- 2007/02/13 09:00
PHST- 2006/11/03 00:00 [received]
PHST- 2006/12/20 00:00 [revised]
PHST- 2007/01/08 00:00 [accepted]
PHST- 2007/02/13 09:00 [pubmed]
PHST- 2007/06/27 09:00 [medline]
PHST- 2007/02/13 09:00 [entrez]
PHST- 2008/04/01 00:00 [pmc-release]
AID - S0014-4886(07)00025-8 [pii]
AID - 10.1016/j.expneurol.2007.01.005 [doi]
PST - ppublish
SO  - Exp Neurol. 2007 Apr;204(2):840-4. doi: 10.1016/j.expneurol.2007.01.005. Epub 
      2007 Jan 13.