[{"key":"dc.contributor.author","value":"Shewchuk, Leann Dawn","language":null},{"key":"dc.date.accessioned","value":"2009-10-05T17:52:07Z","language":null},{"key":"dc.date.available","value":"2009-10-05T17:52:07Z","language":null},{"key":"dc.date.issued","value":"2002","language":null},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/13562","language":null},{"key":"dc.description.abstract","value":"In skeletal muscle, molecular and cellular adaptation occurs in response to changes in functional demand.\r\nThe changes in phenotype are well described, however the signalling mechanisms which lead to\r\nadaptation are poorly understood. Our purpose was to determine whether acute changes in myofibril\r\nintegrity caused by calpain activation are related to changes in myoblast proliferation and differentiation.\r\nWe hypothesized that degradation products of muscle, capable of stimulating myogenesis, are produced\r\nin response to acute exercise. Wistar rats ran downhill on a motorized treadmill (16% grade, 30 m\/min)\r\nfor 60 min or remained sedentary. Saline extracts prepared from hindlimb muscle following exercise\r\nincreased L6 myoblast proliferation and differentiation (p<0.01). Extracts from sedentary animals had\r\nno effect (p=NS). The active factor(s) had an apparent molecular weight of > 10 kDa. A subset of\r\nanimals in each group received E64c, a cysteine protease (calpain) inhibitor. The inhibitor attenuated the\r\nincrease in differentiation associated with exercise (p<0.05), suggesting that a cysteine protease was\r\ninvolved in the release of soluble factors that affect myogenesis. Many of the proteins that undergo\r\nremodelling in response to exercise are calpain substrates, therefore we further hypothesized that calpainderived\r\nmyofibril fragments are capable of stimulating myoblast proliferation and differentiation.\r\nPurified myofibrils were treated with m-calpain in the presence of calcium. The autolysis of calpain was\r\nfollowed under the same conditions in the absence of myofibrils. Both preparations showed equal ability\r\nto stimulate myoblast proliferation and differentiation. Therefore, the primary finding of this study was\r\nthat autolytic fragments of m-calpain stimulate myogenesis and calpain-derived myofibril fragments do\r\nnot. Further studies showed that autolytic fragments of u.-calpain also stimulate myoblast proliferation\r\nand differentiation. The active fragment was a low molecular weight peptide (<10 kDa) and was an early\r\nproduct of calpain autolysis. The results suggest a novel consequence for calpain activation. Overall, the\r\nresults support a relationship between the acute changes in myofibril integrity caused by calpain\r\nactivation and adaptation in muscle.","language":"en"},{"key":"dc.format.extent","value":"4902579 bytes","language":null},{"key":"dc.format.mimetype","value":"application\/pdf","language":null},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":null},{"key":"dc.rights","value":"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.","language":null},{"key":"dc.title","value":"An emerging role for calpain in skeletal muscle adaptation","language":"en"},{"key":"dc.type","value":"Text","language":null},{"key":"dc.degree.name","value":"Doctor of Philosophy - PhD","language":"en"},{"key":"dc.degree.discipline","value":"Interdisciplinary Studies","language":"en"},{"key":"dc.degree.grantor","value":"University of British Columbia","language":null},{"key":"dc.date.graduation","value":"2002-11","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Graduate and Postdoctoral Studies","language":null},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]