PMID- 17161226
OWN - NLM
STAT- MEDLINE
DCOM- 20070220
LR  - 20211203
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 56
IP  - 1
DP  - 2007 Jan
TI  - Sepsis-induced suppression of skeletal muscle translation initiation mediated by 
      tumor necrosis factor alpha.
PG  - 49-57
AB  - Inhibition of translational efficiency is responsible at least in part for the 
      sepsis-induced decrease in protein synthesis observed in skeletal muscle. 
      Moreover, infusion of the inflammatory cytokine tumor necrosis factor alpha 
      (TNF-alpha) into naive rats produces a comparable decrement. Therefore, the 
      purpose of the present study was to determine whether inhibition of TNF action 
      under in vivo conditions could prevent the sepsis-induced decrease in translation 
      initiation observed in the postabsorptive state. To address this aim, sepsis was 
      produced by cecal ligation and puncture (CLP) and rats were studied in the fasted 
      condition 20 to 24 hours thereafter. Both septic and time-matched nonseptic 
      control rats were pretreated with TNF-binding protein (TNF(BP)) before CLP or 
      sham surgery to neutralize endogenously produced TNF. Sepsis altered the 
      distribution of eukaryotic initiation factor 4E (eIF4E) in the gastrocnemius by 
      increasing the amount associated with 4E-BP1 (inactive complex) and decreasing 
      the amount bound to eIF4G (active complex). This change in eIF4E availability was 
      associated with a decreased phosphorylation of 4E-BP1. Furthermore, the 
      phosphorylation of ribosomal protein S6 and mammalian target of rapamycin (mTOR) 
      was also decreased in the gastrocnemius from septic rats. Pretreatment of septic 
      rats with TNF(BP) largely ameliorated the altered distribution of eIF4E as well 
      as the reduced phosphorylation of 4E-BP1, S6, and mTOR. In contrast, sepsis did 
      not change either the total amount or the phosphorylation state of eIF2alpha or 
      eIF2Bepsilon. Furthermore, no sepsis-induced change in eIFs was detected in the 
      slow-twitch soleus muscle. The ability of TNF(BP) to prevent the sepsis-induced 
      alterations in translation initiation was independent of change in plasma insulin 
      and proportional to the insulinlike growth factor I content in blood and muscle 
      but was associated with a reduction in plasma corticosterone. Hence, the 
      decreased constitutive protein synthesis observed in fast-twitch skeletal muscle 
      in response to peritonitis is mediated by a TNF-dependent mechanism affecting 
      mTOR regulation of translation initiation.
FAU - Lang, Charles H
AU  - Lang CH
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State University 
      College of Medicine, Hershey, PA 17033, USA. clang@psu.edu
FAU - Frost, Robert A
AU  - Frost RA
LA  - eng
GR  - GM38032/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Carrier Proteins)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (Eukaryotic Initiation Factor-2B)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - 0 (Insulin)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - Eukaryotic Initiation Factor-2B/metabolism
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Eukaryotic Initiation Factor-4G/metabolism
MH  - Immunoblotting
MH  - Insulin/blood
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Muscle Proteins/*metabolism
MH  - Muscle, Skeletal/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Protein Biosynthesis/*physiology
MH  - Protein Kinases/metabolism
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Tumor Necrosis Factor/administration & dosage/metabolism
MH  - Ribosomal Protein S6/metabolism
MH  - Sepsis/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Tumor Necrosis Factor-alpha/antagonists & 
      inhibitors/genetics/metabolism/*physiology
EDAT- 2006/12/13 09:00
MHDA- 2007/02/21 09:00
CRDT- 2006/12/13 09:00
PHST- 2006/04/24 00:00 [received]
PHST- 2006/08/23 00:00 [accepted]
PHST- 2006/12/13 09:00 [pubmed]
PHST- 2007/02/21 09:00 [medline]
PHST- 2006/12/13 09:00 [entrez]
AID - S0026-0495(06)00318-0 [pii]
AID - 10.1016/j.metabol.2006.08.025 [doi]
PST - ppublish
SO  - Metabolism. 2007 Jan;56(1):49-57. doi: 10.1016/j.metabol.2006.08.025.