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Title: Proteomic analysis of diurnal variation in human skeletal muscle performance
Author: Malik, Z. A.
ISNI:       0000 0004 5992 9957
Awarding Body: Liverpool John Moores University
Current Institution: Liverpool John Moores University
Date of Award: 2015
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Phenotyping of human muscle based on its profile of myosin heavy chain isoforms is commonly used to help understand changes in muscle function. However, in many instances, measureable changes in force output or contractility occur in the absence of any change in myosin heavy chain profile. Therefore, more sophisticated analysis is required. Proteomic techniques including 2-dimensional gel electrophoresis, high- performance liquid chromatography and peptide mass spectrometry can be used to investigate changes in the abundance of hundreds of proteins simultaneously. To date, such techniques have not been used to specifically characterise the human myofibrillar proteome, or study how the myofibrillar proteome relates to muscle outputs such as peak isometric force or the velocity of contraction. This thesis presents a series of studies that develop proteomic techniques for the analysis of myofibrillar proteins as well as optimisation of techniques for measuring the range of muscle output from isometric through to velocity maximum of the human knee extensor muscles in vivo. After optimisation, the proteomic and muscle function measurement were employed to study diurnal variation. Time-of-day differences in sports performance and muscle function are widely reported, and typically, performance is ~10 % greater in the evening compared to the morning. This is consistent with our result in Chapter 3; we investigated this chapter by conducting a battery of muscle performance tests in a population of well-familiarised participants. Our data show that RFD exhibits the greatest diurnal variation (18 %) followed by isometric force (10.2 %). The diurnal variation in IKD data was less robust (range 8.1 - 9.8 %), which may have been due to the lesser precision of this technique compared to MVC and RFD. Therefore MVC and RFD were used in the final study. In final study, this thesis reports significantly (P<0.05) greater peak isometric force (11 %) and rate of force development (16 %) of knee extensor muscles of young strength-trained males in the evening compared to morning. Proteomic analysis of biopsy samples of the vastus lateralis profiled more than 100 myofibrillar protein species and detected 8 significant differences in protein abundance between morning and evening samples. The greatest difference was in the abundance of the slow isoform of myosin binding protein C (MyBPC1), which is known to modulate the activity of actin-bound myosin ATPases. MyBPC1 was resolved to 6 species; therefore the difference in abundance of one species reported here likely represents a change in post-translational modification. Therefore, this thesis provides associational evidence that post-translational modification of MyBPC1 contributes to the diurnal variation in muscle function.
Supervisor: Burniston, J. ; Edwards, B. ; Vanrenterghem, J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: RC1200 Sports Medicine