Sepsis and development impede muscle protein synthesis in neonatal pigs by different ribosomal mechanisms

Pediatr Res. 2011 Jun;69(6):473-8. doi: 10.1203/PDR.0b013e3182176da1.


In muscle, sepsis reduces protein synthesis (MPS) by restraining translation in neonates and adults. Even though protein accretion decreases with development as neonatal MPS rapidly declines by maturation, the changes imposed by development on the sepsis-associated decrease in MPS have not been described. Pigs at 7 and 26 d of age were infused for 8 h with lipopolysaccharide (LPS, endotoxin, 0 and 10 μg · kg⁻¹ · h⁻¹). Fractional MPS rates and translation eukaryotic initiation factor (eIF) activation in muscle were examined (n = 5-7/group). The LPS-induced decrease in MPS was associated with reduced ribosomal and translational efficiency, whereas the age-induced decrease in MPS occurred by decreasing ribosome number. Abundances of mammalian target of rapamycin (mTOR) and S6 decreased, and that of the repressor eIF4E · 4E-binding protein 1 (4EBP1) association increased in 26-d-old pigs--compared with 7-d-old pigs. LPS decreased the abundance of the active eIF4E ·eIF4G association and the phosphorylation of eIF4G across ages, whereas the abundance of eIF4G declined and eIF2α phosphorylation increased with age. Therefore, when lacking anabolic stimulation, the decrease in MPS induced by LPS is associated with reduced ribosomal efficiency and decreased eIF4E ·eIF4G assembly, whereas that induced by development involves reduced ribosomal number, translation factor abundance, and increased eIF2α phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn / metabolism
  • Blood Glucose / metabolism
  • Elongation Factor 2 Kinase / metabolism
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factor-4E / metabolism
  • Eukaryotic Initiation Factor-4G / metabolism
  • Female
  • Insulin / metabolism
  • Lipopolysaccharides / pharmacology
  • Muscle Development / physiology*
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology
  • Pregnancy
  • Protein Biosynthesis*
  • Random Allocation
  • Ribosomes / metabolism*
  • Sepsis / physiopathology*
  • Signal Transduction / physiology
  • Swine


  • Blood Glucose
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factor-4G
  • Insulin
  • Lipopolysaccharides
  • Muscle Proteins
  • Elongation Factor 2 Kinase