|Orellana, Renan -|
|Wilson, Fiona -|
|Gazzaneo, Maria -|
|Suryawan, Agus -|
|Davis, Teresa -|
|Nguyen, Hanh -|
Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 29, 2010
Publication Date: June 1, 2011
Citation: Orellana, R.A., Wilson, F.A., Gazzaneo, M.C., Suryawan, A., Davis, T.A., Nguyen, H.V. 2011. Sepsis and development impede muscle protein synthesis in neonatal pigs by different ribosomal mechanisms. Pediatric Research. 69(6):473-478. Interpretive Summary: This research paper examines how muscle wasting (a decrease in muscle mass) worsens as some animals grow from being a newborn to a more mature pig. This study is important because it will help design nutritional therapies that are adequate to different ages when children are sick and waste muscle and lose growth because of illness.
Technical 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 microg /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/4Ebinding 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 eIF2alpha 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 eIF2alpha phosphorylation.