<p> Resistance exercise and amino acids independently and synergistically stimulate muscle protein synthesis. Unloading of skeletal muscle depresses fasted state muscle protein synthesis, but the effect on the fed state response is unknown. Elucidation of the signaling pathways underlying the regulation of these processes in humans is in its infancy. Therefore, the purpose of this thesis was to determine how resistance exercise, feeding, and unloading interact to affect muscle protein turnover and its markers. In study 1 young men (N=9) underwent an acute bout of unilateral leg resistance exercise with or without feeding, with biopsies 6 h post exercise. Exercise dephosphorylated eiF2Bε and together with feeding potentiated the increase in phosphorylation of p70s6k and rps6. In study 2, 12 young people received primed constant infusions of 13C6-Phe in the fasted state and at one of two i.v. AA infusion rates (low, 42.5 mg/kg/h AA; high: 261 mg/kg/h AA) after 14 d of knee-brace mediated immobilization. Immobilization decreased fasted and fed state myofibrillar protein synthesis at both doses without obviously affecting translational signaling proteins. In study 3, two markers of muscle protein breakdown and oxidative damage were measured in 21 subjects (men, N=13, women, N=8) after 2 d and 14 d of knee-brace mediated immobilization. Protein ubiquitination was elevated after 2 d of immobilization but there was no sustained elevation in ubiquination at 14 d or increases in the 14kDa actin fragment or protein carbonyls and 4-hydroxy-2-nonenal. These studies support the concept that the responses of human muscle to changes in loading are primarily at the level of protein synthesis, and the p70 pathway appears to play a role in mediating the hypertrophic response. The currently known static markers of translational signaling and protein breakdown, however, are not very informative when attempting to account for an underlying molecular mechanism for disuse atrophy. </p> / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/17296 |
| Date | January 2009 |
| Creators | Glover, Elisa I. |
| Contributors | Phillips, Stuart M., Kinesiology |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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