Hesketh, S (2020) The role of individual protein turnover in skeletal muscle adaptation. Doctoral thesis, Liverpool John Moores University.

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Abstract

Skeletal muscle tissue demonstrates a remarkable malleability and can adjust its metabolic and contractile makeup in response to alterations in functional demands. As a result, great diversity exists in muscle physiology, biochemistry and energy metabolism, all of which are underpinned by the functional changes in the abundance of individual proteins. The proteome represents a highly dynamic and versatile entity that coordinates the adaptive response of skeletal muscle through adjustments in individual protein turnover as well as abundance. Until very recently, research relating to protein turnover was largely limited to average synthesis rates of protein mixtures, e.g. from whole muscle homogenates. This project utilises our new methodology, coined dynamic proteome profiling, combining deuterium labelling and advanced proteomic techniques with computational biology, to investigate muscle protein dynamics at the individual protein level. We have used programmed exercise to perturb skeletal muscle in vivo for the purposes of studying two contrasting types of muscle adaptation, each over a chronic 30-day period. The first is an endurance stimulus that induced changes in protein abundance for 50 individual muscle proteins. Of these changes, 30 % were driven by changes in synthesis, 38 % were driven by degradation only and the remaining 32 % by changes in a combination of both synthesis and degradation. We also provide new evidence to demonstrate that in response to resistance exercise training individual proteins increase the rates of protein turnover and can be selectively degraded at varying rates to alter individual protein abundances. As a result, we report, 27 of 91 proteins studied exhibited a change in abundance in response to muscle hypertrophy. Of which 96 % were driven by synthesis and 4 % of proteins were driven by degradation. For the remaining 64 proteins that did not change in abundance, 36 % increased protein turnover, 17 % decreased in protein turnover and 47 % of proteins were unaffected by our resistance exercise training stimulus. This work is the first of its kind and presents a highly novel contribution to the rapidly growing field of exercise proteomics.

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	proteome; exercise; physiology; muscle adaptation
Subjects:	Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > R Medicine (General)
Divisions:	Sport & Exercise Sciences
Date Deposited:	21 Jan 2020 09:16
Last Modified:	08 Nov 2022 14:58
DOI or ID number:	10.24377/LJMU.t.00012055
Supervisors:	Burniston, J
URI:	https://researchonline.ljmu.ac.uk/id/eprint/12055

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