Browsing by Author "McCauley, Sydney R."
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- Diminished satellite cell fusion and S6K1 expression in myotubes derived from skeletal muscle of low birth weight neonatal pigsChen, Ying; Zhu, Haibo; McCauley, Sydney R.; Zhao, Lidan; Johnson, Sally E.; Rhoads, Robert P.; El-Kadi, Samer Wassim (The American Physiological Society, 2017-02-09)Low birth weight (LBWT) is consistently associated with impaired postnatal muscle growth in mammals. Satellite cell (SC)‐mediated myonuclear incorporation precedes protein accumulation in the early stages of postnatal muscle development and growth. The objective of this study was to investigate proliferation and differentiation of SCs and the regulation of protein synthesis signaling in response to insulin‐like growth factor (IGF)‐I stimulation in SC‐derived myotubes of LBWT neonatal pigs. SCs isolated from Longissimus dorsi muscle of LBWT and NBWT pigs (3‐d‐old, n = 8) were cultured and induced to proliferate and differentiate to myotubes in vitro. On day 3 of differentiation, myotubes were fasted in serum‐free media for 3 h and treated with human recombinant R³‐insulin‐like growth factor‐I (rh IGF‐I) at 0, 25, and 50 ng × mL⁻¹ for 30 min. There was no difference in proliferation rates of SCs from LBWT and NBWT pigs. However, LBWT SC fusion was 15% lower (P ≤ 0.05) without a difference in MyoD or myogenin mRNA expression in comparison with NBWT pigs, suggesting SCs are not intrinsically different between the two groups. IGF‐Ι stimulation at physiological concentrations activated downstream effectors of mTOR similarly in myotubes from LBWT and NBWT pigs. However, abundance of ribosomal protein S6 kinase 1(S6K1) was lower in myotubes of LBWT compared to their NBWT siblings (P ≤ 0.05). These results indicate that the modest reduction in SC fusion and S6K1 expression are not the major contributors to the impaired postnatal muscle growth of LBWT pigs.
- Downregulated Translation Initiation Signaling Predisposes Low-Birth-Weight Neonatal Pigs to Slower Rates of Muscle Protein SynthesisChen, Y.; McCauley, Sydney R.; Johnson, Sally E.; Rhoads, Robert P.; El-Kadi, Samer Wassim (Frontiers, 2017-07-11)Low-birth-weight (LBWT) neonates experience restricted muscle growth in their perinatal life. Our aim was to investigate the mechanisms that contribute to slower skeletal muscle growth of LBWT neonatal pigs. Twenty-four 1-day old male LBWT (816 ± 55 g) and normal-birth-weight (NBWT; 1,642 ± 55 g) littermates (n = 12) were euthanized to collect blood and longissimus dorsi (LD) muscle subsamples. Plasma glucose, insulin, and insulin-like growth factor-I (IGF-I) were lower in LBWT compared with NBWT pigs. Muscle IGF-I mRNA expression were lower in LBWT than NBWT pigs. However, IGF-I receptor mRNA and protein abundance was greater in LD of LBWT pigs. Abundance of myostatin and its receptors, and abundance and phosphorylation of smad3 were lower in LBWT LD by comparison with NBWT LD. Abundance of eukaryotic initiation factor (eIF) 4E binding protein 1 and mitogen-activated protein kinase-interacting kinases was lower in muscle of LBWT pigs compared with NBWT siblings, while eIF4E abundance and phosphorylation did not differ between the two groups. Furthermore, phosphorylation of ribosomal protein S6 kinase 1 (S6K1) was less in LBWT muscle, possibly due to lower eIF3e abundance. In addition, abundance and phosphorylation of eIF4G was reduced in LBWT pigs by comparison with NBWT littermates, suggesting translation initiation complex formation is compromised in muscle of LBWT pigs. In conclusion, diminished S6K1 activation and translation initiation signaling are likely the major contributors to impaired muscle growth in LBWT neonatal pigs. The upregulated IGF-I R expression and downregulated myostatin signaling seem to be compensatory responses for the reduction in protein synthesis signaling.