ARS | Publication request: AMINO ACIDS AUGMENT MUSCLE PROTEIN SYNTHESIS IN NEONATAL PIGS DURING ENDOTOXEMIA BY MODULATING TRANSLATION INITIATION

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: March 6, 2006
Publication Date: April 1, 2006
Citation: Orellana, R.A., Escobar, J., Jeyapalan, A.S., Nguyen, H.V., Suryawan, A., Frank, J., Davis, T.A. 2006. Amino acids augment muscle protein synthesis in neonatal pigs during endotoxemia by modulating translation initiation [abstract]. The Federation of American Societies for Experimental Biology Conference: Advancing the Biomedical Frontier, April 1-5, 2006, San Francisco, California. 20(4):Part I, p. A9.

Technical Abstract: In adults, sepsis reduces protein synthesis in skeletal muscle by restraining translation. The effect of sepsis on amino acid-stimulated muscle protein synthesis has not been determined in neonates, a population who is highly anabolic and whose muscle protein synthesis rates are uniquely sensitive to amino acid stimulation. Overnight fasted neonatal pigs were infused for 8 h with endotoxin (LPS, 0 and 10 ug.kg[-1].hr[-1]). Glucose and insulin were maintained at fasting levels, serum amino acids levels were clamped either at fasting or fed (500 or 1000 mmol/dl) levels, fractional protein synthesis rates were determined, and translational control mechanisms were examined. In the presence of fasting serum amino acids levels, LPS reduced protein synthesis in longissiums dorsi (LD) muscle (-20%), increased the inactive eIF4E/4E-BP1 binding (p=0.03), and decreased S6K1 phosphorylation (p=0.03). Raising amino acids to fed levels accelerated muscle protein synthesis rates (controls: +80%; LPS: +57%), increased 4E-BP1 (controls: p=0.02, LPS: p=0.06) and S6K1 (controls: p=0.05; LPS: p=0.04) phosphorylation, and tended to decrease the phosphorylation of eEF2 in muscle of control but not LPS animals. The results suggest that endotoxin reduces the basal rate of muscle protein synthesis in neonates but does not alter the response of muscle protein synthesis to amino acid stimulation.