Skeletal muscle demonstrates a remarkable malleability and can adjust its metabolic and contractile properties in response to changes in environmental stimuli. The proteome represents a highly dynamic and versatile entity that coordinates the adaptive response of skeletal muscle through adjustments in individual protein abundance, modulated by changes in the synthesis and degradation rate of proteins. Previously research relating to protein turnover has been largely limited to average synthesis rates of protein mixtures e.g. from whole/ subfractions of muscle homogenates. This project utilises dynamic proteome profiling which combines deuterium oxide labelling and proteomic techniques with computational biology, to investigate muscle protein dynamics at the individual protein level. This work used 3 in vivo human and rodent exercise models to studying the complexity of dynamic proteome adaptation. Identifying that exercise induced adaptation can occur on the level of protein turnover, independent of classical changes in protein abundance. Which seems of particular importance in counteracting proteostatic stress (i.e. obesity and disease). Subsequently the need to investigate the relationship between protein dynamics and proteome remodelling resulted in the observation that changes in protein abundance do not follow a simple linear trajectory of adaptation. Also, protein specific synthesis rates seemingly undergo time-dependent adaptations when explaining remodelling in the context of an animal model of programmable resistance training. Finally, this thesis provides new evidence to demonstrate that human exercise training results in unique alterations in the rates of protein synthesis and degradation that is training mode and status dependent despite networks of proteins resulting in the same abundance changes. This work raises potential questions as to the extent of exercise induced adaptation explained by modulation of protein synthesis, particularly in the context of endurance training. Whereby changes in degradation are implicated as a key driver of endurance exercise induced proteome remodelling. This work represents some of the first of its kind to present novel details as to the potential roles of protein synthesis, degradation, and turnover rate in modulating differences in skeletal muscle health and function induced by exercise. / Thesis / Candidate in Philosophy
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29948 |
| Date | January 2024 |
| Creators | Stead, Connor |
| Contributors | Phillips, Stuart, Burniston, Jatin, Siekmann, Ivo, Kinesiology |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | Thesis |
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