Calpain-3 is autolyzed and hence activated in human skeletal muscle 24 h following a single bout of eccentric exercise.
The function and normal regulation of calpain-3, a muscle-specific Ca(2+)-dependent protease, is uncertain, although its absence leads to limb-girdle muscular dystrophy type 2A. This study examined the effect of eccentric exercise on calpain-3 autolytic activation, because such exercise is known to damage sarcomeric structures and to trigger adaptive changes that help prevent such damage on subsequent exercise. Six healthy human subjects performed a 30-min bout of one-legged, eccentric, knee extensor exercise. Torque measurements, vastus lateralis muscle biopsies, and venous blood samples were taken before and up to 7 days following the exercise. Peak isometric muscle torque was depressed immediately and at 3 h postexercise and recovered by 24 h, and serum creatine kinase concentration peaked at 24 h postexercise. The amount of autolyzed calpain-3 was unchanged immediately and 3 h after exercise, but increased markedly (from approximately 16% to approximately 35% of total) 24 h after the exercise, and returned to preexercise levels within 7 days. In contrast, the eccentric exercise produced little autolytic activation of the ubiquitous Ca(2+)-activated protease, mu-calpain. Eccentric exercise is the first physiological circumstance shown to result in calpain-3 activation in vivo.
Murphy
Robyn M
RM
Department of Zoology, La Trobe University, Victoria 3086, Australia. r.murphy@latrobe.edu.au
Goodman
Craig A
CA
McKenna
Michael J
MJ
Bennie
Jason
J
Leikis
Murray
M
Lamb
Graham D
GD
D000293:Adolescent; D000328:Adult; D002154:Calpain / Q000378:metabolism*; D003402:Creatine Kinase / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D052097:Quadriceps Muscle / Q000378:metabolism*; D013997:Time Factors; D019415:Torque
D009124:Muscle Proteins; D003402:Creatine Kinase; C105884:CAPN3 protein, human; D002154:Calpain; C449002:mu-calpain