UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

An emerging role for calpain in skeletal muscle adaptation Shewchuk, Leann Dawn


In skeletal muscle, molecular and cellular adaptation occurs in response to changes in functional demand. The changes in phenotype are well described, however the signalling mechanisms which lead to adaptation are poorly understood. Our purpose was to determine whether acute changes in myofibril integrity caused by calpain activation are related to changes in myoblast proliferation and differentiation. We hypothesized that degradation products of muscle, capable of stimulating myogenesis, are produced in response to acute exercise. Wistar rats ran downhill on a motorized treadmill (16% grade, 30 m/min) for 60 min or remained sedentary. Saline extracts prepared from hindlimb muscle following exercise increased L6 myoblast proliferation and differentiation (p<0.01). Extracts from sedentary animals had no effect (p=NS). The active factor(s) had an apparent molecular weight of > 10 kDa. A subset of animals in each group received E64c, a cysteine protease (calpain) inhibitor. The inhibitor attenuated the increase in differentiation associated with exercise (p<0.05), suggesting that a cysteine protease was involved in the release of soluble factors that affect myogenesis. Many of the proteins that undergo remodelling in response to exercise are calpain substrates, therefore we further hypothesized that calpainderived myofibril fragments are capable of stimulating myoblast proliferation and differentiation. Purified myofibrils were treated with m-calpain in the presence of calcium. The autolysis of calpain was followed under the same conditions in the absence of myofibrils. Both preparations showed equal ability to stimulate myoblast proliferation and differentiation. Therefore, the primary finding of this study was that autolytic fragments of m-calpain stimulate myogenesis and calpain-derived myofibril fragments do not. Further studies showed that autolytic fragments of u.-calpain also stimulate myoblast proliferation and differentiation. The active fragment was a low molecular weight peptide (<10 kDa) and was an early product of calpain autolysis. The results suggest a novel consequence for calpain activation. Overall, the results support a relationship between the acute changes in myofibril integrity caused by calpain activation and adaptation in muscle.

Item Media

Item Citations and Data


For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.