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Am J Physiol Endocrinol Metab (June 6, 2006). doi:10.1152/ajpendo.00069.2006
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Submitted on February 8, 2006
Accepted on May 25, 2006

Developmental Regulation of the Activation of Signaling Components Leading to Translation Initiation in Skeletal Muscle of Neonatal Pigs

Agus Suryawan1, Jeffery Escobar1, Jason W. Frank1, Hanh V. Nguyen1, and Teresa A. Davis1*

1 Department of Pediatrics, United States Department Agriculture/Agriculture Research Service, Children's Nutrition Research Center, Baylor College of Medi, Houston, Texas, United States

* To whom correspondence should be addressed. E-mail: tdavis{at}bcm.edu.

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 fasting 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 homologue deleted on chromosome 10 (PTEN), protein phosphatase 2A (PP2A), and tuberous sclerosis complex 1/2 (TSC1/2) increased with age. Ser/Thr phosphorylation of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), which down-regulates insulin signaling, and the activation of AMP-activated protein kinase (AMPK), 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 eIF-4E 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 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.




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