Regulation of muscle protein synthesis in neonatal pigs during prolonged XXXX .

@entity558 @entity1522 @entity308 @entity5694 @entity535 @entity55923 @entity413
In adults, protein synthesis in skeletal muscle is reduced by as much as 50% after a septic challenge, and is associated with repression of translation initiation. Neonates are highly anabolic and their muscle protein synthesis rates are elevated and uniquely sensitive to @entity535 and insulin stimulation. In the present study, neonatal piglets were infused with Endotoxin (lipopolysaccharide, @entity558 ) for 20 h at 0 (n = 6) and 13 microg/kg*h (n = 8). During the last 2 h, @entity413 and an @entity535 mixture were infused to attain fed plasma concentrations of @entity1522 , @entity413 , and insulin. Fractional protein synthesis rates and translational control mechanisms were examined. @entity558 reduced protein synthesis in glycolytic muscles by only 13% and had no significant effect in oxidative muscles. This @entity308 was associated with reductions in the phosphorylation of 4E-BP1 (-31%) and S6 K1 (-78%), and a decrease in eIF4G binding to @entity55923 (-62%), an event required for formation of the active mRNA binding complex. By comparison, @entity558 increased protein synthesis in the liver (+29%), spleen (+32%), and kidney (+27%), and in the liver, this increase was associated with augmented eIF4G to @entity55923 binding (+88%). In muscle and liver, @entity558 did not alter eIF2B activity, an event that regulates initiator met-tRNA(i) binding to the 40S ribosomal complex. These findings suggest that during sustained @entity5694 , the high rate of neonatal muscle protein synthesis is largely maintained in the presence of substrate supply, despite profound changes in translation initiation factors that modulate the mRNA binding step in translation initiation.
