PMID- 21775707
OWN - NLM
STAT- MEDLINE
DCOM- 20111115
LR  - 20211203
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 301
IP  - 4
DP  - 2011 Oct
TI  - Endotoxin transiently inhibits protein synthesis through Akt and MAPK mediating 
      pathways in C2C12 myotubes.
PG  - C895-902
LID - 10.1152/ajpcell.00387.2010 [doi]
AB  - In this study, the effect of lipopolysaccharide (LPS) on protein synthesis (PS) 
      and intracellular signaling factors that regulate it have been investigated in 
      C2C12 murine-derived myotubes. In particular, the role of Akt/mammalian target of 
      rapamycin (mTOR) and the mitogen-activated protein kinases (MAPKs) [p38 and 
      extracelluar regulated protein kinase (ERK1/2)] have been examined. The direct 
      effect of LPS on PS was measured at 3 and 18 h. LPS significantly decreased PS at 
      3 h but not at the 18-h time point. This effect was preceded by decreased Akt 
      phosphorylation at 5 and 30 min after LPS administration. The mTOR 
      phosphorylation exhibited a long time dose-dependent increase at all the time 
      points. Similarly, the activity-related phosphorylation of p38 and ERK1/2 
      significantly increased in a time- and dose-dependent manner at all the time 
      points. Polymyxin B abolished the LPS-induced decrease in PS rate. The 
      phosphatidylinositol 3-kinase inhibitor LY-0294002 in combination with LPS 
      significantly decreased the rate of PS by 81% and alone by 66%, respectively, for 
      the 3- and 18-h time points, whereas p38 and ERK inhibitors in combination with 
      LPS significantly decreased the rate PS rate at the 18-h time point by 41% and 
      59%, respectively, compared with control cells. In conclusion, LPS alone 
      transiently decreased the rate of PS by 50% at 3 h; this effect is most likely 
      mediated via the Toll-like receptor 4 (TLR4)-Akt/mTOR pathway, and both p38 and 
      ERK when inhibited in the presence of LPS at 3 h have a similar effect in 
      preventing the LPS-induced reduction in PS.
FAU - Tarabees, R
AU  - Tarabees R
AD  - School of Veterinary Medicine and Science, Sutton Bonington Campus, Univ. of 
      Nottingham, Loughborough, UK.
FAU - Hill, D
AU  - Hill D
FAU - Rauch, C
AU  - Rauch C
FAU - Barrow, P A
AU  - Barrow PA
FAU - Loughna, P T
AU  - Loughna PT
LA  - eng
PT  - Journal Article
DEP - 20110720
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Muscle Proteins)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/*drug effects
MH  - Lipopolysaccharides/administration & dosage/*pharmacology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/genetics/*metabolism
MH  - Muscle Fibers, Skeletal/drug effects/*metabolism
MH  - Muscle Proteins/genetics/*metabolism
MH  - Myoblasts
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Time Factors
EDAT- 2011/07/22 06:00
MHDA- 2011/11/16 06:00
CRDT- 2011/07/22 06:00
PHST- 2011/07/22 06:00 [entrez]
PHST- 2011/07/22 06:00 [pubmed]
PHST- 2011/11/16 06:00 [medline]
AID - ajpcell.00387.2010 [pii]
AID - 10.1152/ajpcell.00387.2010 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2011 Oct;301(4):C895-902. doi: 
      10.1152/ajpcell.00387.2010. Epub 2011 Jul 20.