PMID- 20554928
OWN - NLM
STAT- MEDLINE
DCOM- 20101006
LR  - 20211020
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 299
IP  - 3
DP  - 2010 Sep
TI  - BCATm deficiency ameliorates endotoxin-induced decrease in muscle protein 
      synthesis and improves survival in septic mice.
PG  - R935-44
LID - 10.1152/ajpregu.00297.2010 [doi]
AB  - Endotoxin (LPS) and sepsis decrease mammalian target of rapamycin (mTOR) activity 
      in skeletal muscle, thereby reducing protein synthesis. Our study tests the 
      hypothesis that inhibition of branched-chain amino acid (BCAA) catabolism, which 
      elevates circulating BCAA and stimulates mTOR, will blunt the LPS-induced 
      decrease in muscle protein synthesis. Wild-type (WT) and mitochondrial 
      branched-chain aminotransferase (BCATm) knockout mice were studied 4 h after 
      Escherichia coli LPS or saline. Basal skeletal muscle protein synthesis was 
      increased in knockout mice compared with WT, and this change was associated with 
      increased eukaryotic initiation factor (eIF)-4E binding protein-1 (4E-BP1) 
      phosphorylation, eIF4E.eIF4G binding, 4E-BP1.raptor binding, and eIF3.raptor 
      binding without a change in the mTOR.raptor complex in muscle. LPS decreased 
      muscle protein synthesis in WT mice, a change associated with decreased 4E-BP1 
      phosphorylation as well as decreased formation of eIF4E.eIF4G, 4E-BP1.raptor, and 
      eIF3.raptor complexes. In BCATm knockout mice given LPS, muscle protein synthesis 
      only decreased to values found in vehicle-treated WT control mice, and this 
      ameliorated LPS effect was associated with a coordinate increase in 
      4E-BP1.raptor, eIF3.raptor, and 4E-BP1 phosphorylation. Additionally, the 
      LPS-induced increase in muscle cytokines was blunted in BCATm knockout mice, 
      compared with WT animals. In a separate study, 7-day survival and muscle mass 
      were increased in BCATm knockout vs. WT mice after polymicrobial peritonitis. 
      These data suggest that elevating blood BCAA is sufficient to ameliorate the 
      catabolic effect of LPS on skeletal muscle protein synthesis via alterations in 
      protein-protein interactions within mTOR complex-1, and this may provide a 
      survival advantage in response to bacterial infection.
FAU - Lang, Charles H
AU  - Lang CH
AD  - Department of Cellular and Molecular Physiology, and Surgery, Pennsylvania State 
      University College of Medicine, Hershey, Pennsylvania, USA. clang@psu.edu
FAU - Lynch, Christopher J
AU  - Lynch CJ
FAU - Vary, Thomas C
AU  - Vary TC
LA  - eng
GR  - R01 GM038032/GM/NIGMS NIH HHS/United States
GR  - GM-39277/GM/NIGMS NIH HHS/United States
GR  - DK-062880/DK/NIDDK NIH HHS/United States
GR  - GM-38032/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100616
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 (Amino Acids, Branched-Chain)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Muscle Proteins)
RN  - EC 2.6.1. (Bcat1 protein, mouse)
RN  - EC 2.6.1.- (Transaminases)
SB  - IM
MH  - Amino Acids, Branched-Chain/metabolism
MH  - Animals
MH  - Escherichia coli
MH  - Gene Expression Regulation/physiology
MH  - Lipopolysaccharides/*toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondria/metabolism
MH  - Muscle Proteins/genetics/*metabolism
MH  - Sepsis/*metabolism/mortality
MH  - Transaminases/genetics/*metabolism
PMC - PMC2944428
EDAT- 2010/06/18 06:00
MHDA- 2010/10/07 06:00
PMCR- 2011/09/01
CRDT- 2010/06/18 06:00
PHST- 2010/06/18 06:00 [entrez]
PHST- 2010/06/18 06:00 [pubmed]
PHST- 2010/10/07 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - ajpregu.00297.2010 [pii]
AID - R-00297-2010 [pii]
AID - 10.1152/ajpregu.00297.2010 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R935-44. doi: 
      10.1152/ajpregu.00297.2010. Epub 2010 Jun 16.