Document Detail

Activation of skeletal muscle calpain-3 by eccentric exercise in humans does not result in its translocation to the nucleus or cytosol.
MedLine Citation:
PMID:  21836041     Owner:  NLM     Status:  MEDLINE    
The skeletal muscle-specific calpain-3 protease is likely involved in muscle repair, although the mechanism is not known. Physiological activation of calpain-3 occurs 24 h following eccentric exercise in humans. Functional consequences of calpain-3 activation are not known; however, calpain-3 has been suggested to be involved in nuclear signaling via NF-κB. To test this and help identify how/where calpain-3 acts, we investigated whether calpain-3 autolysis (hence, activation) following eccentric exercise results in translocation from its normal myofibrillar location to the nucleus or the cytosol. In resting human skeletal muscle, the majority (87%) of calpain-3 was present in myofibrillar fractions, with only a small proportion (<10%) in an autolyzed state. Enriched nuclear fractions contained ∼8% of the total calpain-3, which was present in a predominantly (>80%) autolyzed state. Using freshly dissected human muscle fibers to identify freely diffusible proteins, we showed that only ∼5% of the total calpain-3 pool was cytosolic. At 3 and 24 h following eccentric step exercise, there was an ∼70% increase in autolysis in whole muscle samples (n = 11, P < 0.05, by 1-way ANOVA with repeated measures and Newman-Keuls post hoc analysis). This exercise-induced autolysis was attributed to myofibrillar-bound calpain-3, since neither the amount of calpain-3 nor the proportion autolyzed was significantly changed in enriched nuclear or cytosolic fractions following the exercise intervention. We present a model for calpain-3 localization at rest and following activation in human skeletal muscle and suggest that the functional importance of calpain-3 remains predominantly tightly associated with its localization within the myofibrillar compartment.
Robyn M Murphy; Kristian Vissing; Heidy Latchman; Cedric Lamboley; Michael J McKenna; Kristian Overgaard; Graham D Lamb
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-11
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  111     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-18     Completed Date:  2012-06-05     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1448-58     Citation Subset:  IM    
Dept. of Zoology, La Trobe Univ., VIC 3086, Australia.
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MeSH Terms
Autolysis / metabolism
Calpain / metabolism*
Cell Nucleus / metabolism*
Cytosol / metabolism*
Exercise / physiology*
Muscle Proteins / metabolism*
Muscle, Skeletal / metabolism*,  physiology
Myofibrils / metabolism
NF-kappa B / metabolism
Protein Transport / physiology*
Young Adult
Reg. No./Substance:
0/Muscle Proteins; 0/NF-kappa B; EC 3.4.22.-/CAPN3 protein, human; EC 3.4.22.-/Calpain

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