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

Abstract:

: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.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Orellana RA,Wilson FA,Gazzaneo MC,Suryawan A,Davis TA,Nguyen HV

doi

10.1203/PDR.0b013e3182176da1

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

473-8

issue

6

eissn

0031-3998

issn

1530-0447

journal_volume

69

pub_type

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