| The biological response to exercise-induced muscle injury involves a complex interaction between systems that bear loads, react to these loads, and then respond by repairing damaged tissue and initiating adaptations. Proteins in muscle that sense, bear, and react to load, therefore, play an important role in muscle functioning. This dissertation examines some of the mechanisms behind these changes by exploring the function of a select set of load-sensing proteins.; First examined was the muscle specific intermediate filament protein, desmin. It was noted that despite a small decrease in the amount of desmin in a muscle fiber soon after eccentric contraction-induced injury, there was a compensatory increase in desmin concentration upon recovery. This effect was relatively small, however, so to identify other proteins that might be playing a role in the recovery to exercise-induced injury, a non-invasive model of exercise in the mouse was developed, and microarray technology used to identify candidate genes that were upregulated in response to muscle injury. Two important gene families were identified: the Muscle Ankyrin Repeat Proteins (MARP) and muscle LIM protein. Both of these genes were found to be upregulated specifically after eccentric exercise as compared to both passive stretch and isometric contractions, and were therefore excellent candidates for participating in the eccentric contraction recovery process.; Finally, the role of these novel genes in normal muscle structure and physiology was examined. The MARP family was found to influence muscle passive mechanical properties, serving to strengthen and regulate sarcomere length and increase the mechanical integrity of the fiber. In addition, MARPs were shown to be negative regulators of muscle regeneration, such that MARP knockout animals had improved signs of recovery compared to controls. MLP, on the other hand, was shown to play a role in the maintenance of slow muscle fibers and in the positive regulation of muscle regeneration. Both genes, therefore, might be considered stress sensors, serving both mechanical and gene regulatory roles. The dynamic interplay between the positive influence of MLP and the negative influence of the MARPs may contribute to the normal recovery process after exercise-induced injury. |
