PMID- 24226028
OWN - NLM
STAT- MEDLINE
DCOM- 20140226
LR  - 20211203
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 306
IP  - 1
DP  - 2014 Jan 1
TI  - Chronic alcohol consumption disrupts myocardial protein balance and function in 
      aged, but not adult, female F344 rats.
PG  - R23-33
LID - 10.1152/ajpregu.00414.2013 [doi]
AB  - The purpose of this study was to assess whether the deleterious effect of chronic 
      alcohol consumption differs in adult and aged female rats. To address this aim, 
      adult (4 mo) and aged (18 mo) F344 rats were fed a nutritionally complete liquid 
      diet containing alcohol (36% total calories) or an isocaloric isonitrogenous 
      control diet for 20 wk. Cardiac structure and function, assessed by 
      echocardiography, as well as myocardial protein synthesis and proteolysis did not 
      differ in either alcohol- versus control-fed adult rats or in adult versus aged 
      control-fed rats. In contrast, cardiac function was impaired in alcohol-fed aged 
      rats compared with age-matched control rats. Additionally, alcohol feeding 
      decreased cardiac protein synthesis that was associated with decreased 
      phosphorylation of 4E-BP1 and S6K1. This reduction in mammalian target of 
      rapamycin (mTOR) kinase activity was associated with reduced eIF3f and binding of 
      both Raptor and eIF4G to eIF3. Proteasome activity was increased in alcohol-fed 
      aged rats with a coordinate elevation in the E3 ligases atrogin-1 and muscle 
      RING-finger protein-1 (MuRF1). These changes were associated with increased 
      regulated in development and DNA damage response 1 (REDD1) and phosphorylation of 
      AMP-activated protein kinase (AMPK) but no increase in AKT or forkhead 
      transcription factor (FOXO)3 phosphorylation. Finally, markers of autophagy 
      (e.g., LC3B, Atg7, Atg12) and TNF-alpha were increased to a greater extent in 
      alcohol-fed aged rats. These data demonstrate that aged female rats exhibit an 
      enhanced sensitivity to alcohol compared with adult animals. Our data are 
      consistent with a model whereby alcohol increases proteolysis via 
      FOXO-independent increase in atrogin-1, which degrades eIF3f and therefore 
      impairs formation of a functional preinitiation complex and protein synthesis.
FAU - Lang, Charles H
AU  - Lang CH
AD  - Department of Cellular and Molecular Physiology, and.
FAU - Korzick, Donna H
AU  - Korzick DH
LA  - eng
GR  - R37 AA011290/AA/NIAAA NIH HHS/United States
GR  - AA019403/AA/NIAAA NIH HHS/United States
GR  - R01 HL-091097/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131113
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Muscle Proteins)
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.3.2.27 (Fbxo32 protein, rat)
RN  - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Aging
MH  - *Alcohol Drinking
MH  - Animals
MH  - Ethanol/*pharmacology
MH  - Female
MH  - Heart/*drug effects
MH  - Muscle Proteins/*metabolism
MH  - Muscle, Skeletal/metabolism
MH  - Myocardium/*metabolism
MH  - Phosphorylation/physiology
MH  - Rats
MH  - Rats, Inbred F344
MH  - SKP Cullin F-Box Protein Ligases/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3921304
OTO - NOTNLM
OT  - atrophy
OT  - eIF3
OT  - heart
OT  - mTOR
OT  - protein degradation
OT  - protein synthesis
EDAT- 2013/11/15 06:00
MHDA- 2014/02/27 06:00
PMCR- 2015/01/01
CRDT- 2013/11/15 06:00
PHST- 2013/11/15 06:00 [entrez]
PHST- 2013/11/15 06:00 [pubmed]
PHST- 2014/02/27 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - ajpregu.00414.2013 [pii]
AID - R-00414-2013 [pii]
AID - 10.1152/ajpregu.00414.2013 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2014 Jan 1;306(1):R23-33. doi: 
      10.1152/ajpregu.00414.2013. Epub 2013 Nov 13.