PMID- 17020909
OWN - NLM
STAT- MEDLINE
DCOM- 20070220
LR  - 20131121
IS  - 0735-0414 (Print)
IS  - 0735-0414 (Linking)
VI  - 41
IP  - 6
DP  - 2006 Nov-Dec
TI  - Cardiac overexpression of metallothionein rescues chronic alcohol intake-induced 
      cardiomyocyte dysfunction: role of Akt, mammalian target of rapamycin and 
      ribosomal p70s6 kinase.
PG  - 585-92
AB  - AIMS: Reduced insulin sensitivity following alcohol intake plays a role in 
      alcohol-induced organ damage although its precise mechanism is undefined. This 
      study was designed to examine the effect of cardiac overexpression of the 
      antioxidant metallothionein on alcohol-induced cardiac contractile dysfunction 
      and post-receptor insulin signaling. METHODS: FVB and metallothionein mice were 
      fed a 4% alcohol diet for 16 weeks. Cardiomyocyte contractile function was 
      evaluated including peak shortening (PS), time-to-PS (TPS), and 
      time-to-relengthening (TR(90)). Post-insulin receptor signaling molecules Akt, 
      mammalian target of rapamycin (mTOR), and ribosomal p70s6 kinase (p70s6k) were 
      evaluated using western blot analysis. Akt1 kinase activity was assayed with a 
      phosphotransferase kit. RESULTS: Alcohol intake dampened whole body glucose 
      tolerance, depressed PS, shortened TPS, and prolonged TR(90), which were 
      abrogated by metallothionein with the exception of glucose intolerance. Our 
      results revealed reduced expression of total Akt, phosphorylated mTOR, and 
      phosphorylated p70s6k-to-p70s6k ratio as well as Akt1 kinase activity in alcohol 
      consuming FVB mice. Phosphorylated Akt, total mTOR, and phosphorylated p70s6k 
      were unaffected by alcohol. Metallothionein ablated reduced Akt protein and 
      kinase activity without affecting any other proteins or their phosphorylation. 
      CONCLUSION: In summary, our data suggest that chronic alcohol intake interrupted 
      cardiac contractile function and Akt/mTOR/p70s6k signaling. Akt but unlikely mTOR 
      and p70s6k may contribute to metallothionein-elicited cardiac protective 
      response.
FAU - Li, Qun
AU  - Li Q
AD  - Division of Pharmaceutical Sciences, Center for Cardiovascular Research and 
      Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.
FAU - Ren, Jun
AU  - Ren J
LA  - eng
GR  - 1R01 AA013412-01A2/AA/NIAAA NIH HHS/United States
GR  - 1R15AA/HL13575-01/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061004
PL  - England
TA  - Alcohol Alcohol
JT  - Alcohol and alcoholism (Oxford, Oxfordshire)
JID - 8310684
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Insulin)
RN  - 9038-94-2 (Metallothionein)
RN  - EC 2.7.11.1 (Akt1 protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - IY9XDZ35W2 (Glucose)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Alcohol Drinking/*epidemiology
MH  - Animals
MH  - Anti-Bacterial Agents/administration & dosage/*pharmacology
MH  - Blotting, Western
MH  - *Cardiomyopathy, Alcoholic/genetics/metabolism/physiopathology
MH  - Chronic Disease
MH  - Glucose/metabolism
MH  - Immunoprecipitation
MH  - Insulin/metabolism
MH  - Metallothionein/*drug effects/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocytes, Cardiac/*drug effects/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*drug effects/*genetics
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*drug effects/*genetics
MH  - Sirolimus/administration & dosage/*pharmacology
EDAT- 2006/10/06 09:00
MHDA- 2007/02/21 09:00
CRDT- 2006/10/06 09:00
PHST- 2006/10/06 09:00 [pubmed]
PHST- 2007/02/21 09:00 [medline]
PHST- 2006/10/06 09:00 [entrez]
AID - agl080 [pii]
AID - 10.1093/alcalc/agl080 [doi]
PST - ppublish
SO  - Alcohol Alcohol. 2006 Nov-Dec;41(6):585-92. doi: 10.1093/alcalc/agl080. Epub 2006 
      Oct 4.