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Activation of skeletal muscle calpain-3 by eccentric exercise in humans does not result in its translocation to the nucleus or cytosol

Murphy, Robyn and Vissing, Kristian and Latchman, Heidy and Lamboley, C. R and McKenna, Michael J and Overgaard, Kristian and Lamb, G. D (2011) Activation of skeletal muscle calpain-3 by eccentric exercise in humans does not result in its translocation to the nucleus or cytosol. Journal of Applied Physiology, 111 (5). pp. 1448-1458. ISSN 8750-7587 (print) 1522-1601 (online)

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: ResPubID23905, ResPubID24309, muscle injury, calcium-dependent protease, calpains, nuclear, cytosolic
Subjects: Faculty/School/Research Centre/Department > Institute of Sport, Exercise and Active Living (ISEAL)
FOR Classification > 1116 Medical Physiology
SEO Classification > 970111 Expanding Knowledge in the Medical and Health Sciences
Depositing User: VUIR
Date Deposited: 27 Aug 2012 07:13
Last Modified: 16 Mar 2015 06:07
URI: http://vuir.vu.edu.au/id/eprint/9249
DOI: 10.1152/japplphysiol.00441.2011
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Citations in Scopus: 8 - View on Scopus

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