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Title: Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs

Author
item Suryawan, Agus
item ESCOBAR, JEFFERY - BAYLOR COLL OF MEDICINE
item FRANK, JASON - BAYLOR COLL OF MEDICINE
item NGUYEN, HANH - BAYLOR COLL OF MEDICINE
item Davis, Teresa

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/21/2006
Publication Date: 6/6/2006
Citation: Suryawan, A., Escobar, J., Frank, J.W., Nguyen, H.V., Davis, T.A. 2006. Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs. American Journal of Physiology, Endocrinology and Metabolism. 291(4):E849-E859.

Interpretive Summary: Skeletal muscle grows at a very rapid rate in new-born pigs. This is due in part to higher sensitivity of skeletal muscle to make more proteins (protein synthesis) from substrates (amino acids) that are obtained after eating. The ability to make muscle protein is developmentally regulated. In this study, we found that the activation of signaling components of protein synthesis apparatus (mTOR, eIF-4EBP1, eIF-4G, S6K1, and rpS6) is higher in younger pigs (7-day-old pigs) compared to older pigs (26-day-old pigs). In conclusion, new-born pigs have higher ability to make muscle protein compared to older pigs which is due in part to higher activation of protein synthesis apparatus.

Technical Abstract: The rapid growth of neonates is driven by high rates of skeletal muscle protein synthesis. This high rate of protein synthesis, which is induced by feeding, declines with development. Overnight-fasted 7- and 26-day-old pigs either remained fasted or were refed, and the abundance and phosphorylation of growth factor- and nutrient-induced signaling components that regulate mRNA translation initiation were measured in skeletal muscle and liver. In muscle, but not liver, the activation of inhibitors of protein synthesis, phosphatase and tensin homolog deleted on chromosome 10, protein phosphatase 2A, and tuberous sclerosis complex 1/2 increased with age. Serine/threonine phosphorylation of the insulin receptor and insulin receptor substrate-1, which downregulates insulin signaling, and the activation of AMP-activated protein kinase, an inhibitor of protein synthesis, were unaffected by age and feeding in muscle and liver. Activation of positive regulators of protein synthesis, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), and eIF4E-binding protein-1 (4E-BP1) decreased with age in muscle but not liver. Feeding enhanced mTOR, S6K1, and 4E-BP1 activation in muscle, and this response decreased with age. In liver, activation of S6K1 and 4E-BP1, but not mTOR, was increased by feeding but was unaffected by age. Raptor abundance and the association between raptor and mTOR were greater in 7- than in 26-day-old pigs. The results suggest that the developmental decline in skeletal muscle protein synthesis is due in part to developmental regulation of the activation of growth factor and nutrient-signaling components.