PMID- 20150243
OWN - NLM
STAT- MEDLINE
DCOM- 20100506
LR  - 20211020
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 298
IP  - 5
DP  - 2010 May
TI  - Analysis of the liver mitochondrial proteome in response to ethanol and 
      S-adenosylmethionine treatments: novel molecular targets of disease and 
      hepatoprotection.
PG  - G732-45
LID - 10.1152/ajpgi.00332.2009 [doi]
AB  - S-adenosylmethionine (SAM) minimizes alcohol hepatotoxicity; however, the 
      molecular mechanisms responsible for SAM hepatoprotection remain unknown. Herein, 
      we use proteomics to determine whether the hepatoprotective action of SAM against 
      early-stage alcoholic liver disease is linked to alterations in the mitochondrial 
      proteome. For this, male rats were fed control or ethanol-containing liquid diets 
      +/- SAM and liver mitochondria were prepared for proteomic analysis. 
      Two-dimensional isoelectric focusing (2D IEF/SDS-PAGE) and blue native gel 
      electrophoresis (BN-PAGE) were used to determine changes in matrix and oxidative 
      phosphorylation (OxPhos) proteins, respectively. SAM coadministration minimized 
      alcohol-dependent inflammation and preserved mitochondrial respiration. SAM 
      supplementation preserved liver SAM levels in ethanol-fed rats; however, 
      mitochondrial SAM levels were increased by ethanol and SAM treatments. With use 
      of 2D IEF/SDS-PAGE, 30 proteins showed significant changes in abundance in 
      response to ethanol, SAM, or both. Classes of proteins affected by ethanol and 
      SAM treatments were chaperones, beta oxidation proteins, sulfur metabolism 
      proteins, and dehydrogenase enzymes involved in methionine, glycine, and choline 
      metabolism. BN-PAGE revealed novel changes in the levels of 19 OxPhos proteins in 
      response to ethanol, SAM, or both. Ethanol- and SAM-dependent alterations in the 
      proteome were not linked to corresponding changes in gene expression. In 
      conclusion, ethanol and SAM treatment led to multiple changes in the liver 
      mitochondrial proteome. The protective effects of SAM against alcohol toxicity 
      are mediated, in part, through maintenance of proteins involved in key 
      mitochondrial energy conserving and biosynthetic pathways. This study 
      demonstrates that SAM may be a promising candidate for treatment of alcoholic 
      liver disease.
FAU - Andringa, Kelly K
AU  - Andringa KK
AD  - Dept. of Environmental Health Sciences, Univ. of Alabama at Birmingham, 35294, 
      USA.
FAU - King, Adrienne L
AU  - King AL
FAU - Eccleston, Heather B
AU  - Eccleston HB
FAU - Mantena, Sudheer K
AU  - Mantena SK
FAU - Landar, Aimee
AU  - Landar A
FAU - Jhala, Nirag C
AU  - Jhala NC
FAU - Dickinson, Dale A
AU  - Dickinson DA
FAU - Squadrito, Giuseppe L
AU  - Squadrito GL
FAU - Bailey, Shannon M
AU  - Bailey SM
LA  - eng
GR  - P30 AR050948/AR/NIAMS NIH HHS/United States
GR  - DK73775/DK/NIDDK NIH HHS/United States
GR  - S10 RR011329/RR/NCRR NIH HHS/United States
GR  - P30 DK74038/DK/NIDDK NIH HHS/United States
GR  - P30 DK074038/DK/NIDDK NIH HHS/United States
GR  - P50 AT00477/AT/NCCIH NIH HHS/United States
GR  - P30 CA13148/CA/NCI NIH HHS/United States
GR  - U54 CA100949/CA/NCI NIH HHS/United States
GR  - AA15172/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100211
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Proteome)
RN  - 3K9958V90M (Ethanol)
RN  - 7LP2MPO46S (S-Adenosylmethionine)
RN  - 979-92-0 (S-Adenosylhomocysteine)
SB  - IM
MH  - Animals
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Ethanol/*pharmacology
MH  - Liver Diseases, Alcoholic/*prevention & control
MH  - Male
MH  - Mitochondria, Liver/chemistry/*drug effects/*metabolism
MH  - Mitochondrial Proteins/analysis
MH  - Oxygen Consumption/drug effects
MH  - Proteome/*drug effects
MH  - Proteomics
MH  - Rats
MH  - S-Adenosylhomocysteine/metabolism
MH  - S-Adenosylmethionine/metabolism/*pharmacology
MH  - Transcription, Genetic/drug effects
PMC - PMC2867419
EDAT- 2010/02/13 06:00
MHDA- 2010/05/07 06:00
PMCR- 2011/05/01
CRDT- 2010/02/13 06:00
PHST- 2010/02/13 06:00 [entrez]
PHST- 2010/02/13 06:00 [pubmed]
PHST- 2010/05/07 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - ajpgi.00332.2009 [pii]
AID - GI-00332-2009 [pii]
AID - 10.1152/ajpgi.00332.2009 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G732-45. doi: 
      10.1152/ajpgi.00332.2009. Epub 2010 Feb 11.