| Activation of skeletal muscle calpain-3 by eccentric exercise in humans does not result in its translocation to the nucleus or cytosol. | |
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MedLine Citation:
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PMID: 21836041 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 24h 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 NFkB. To test this and help identify how/where calpain-3 acts, we investigated whether calpain-3 autolysis (and hence activation) following eccentric exercise results in translocation from its normal myofibrillar location to either the nucleus or 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 were found to contain ~8% of the total calpain-3, which was present in a predominantly autolyzed state (>80%). Using freshly dissected human muscle fibers to identify freely diffusible proteins, we showed that only ~5% of the total calpain-3 pool was cytosolic. Three and 24h following eccentric step exercise, there was ~1.7 fold increase in autolysis in whole muscle samples (n=11, p<0.05, one-way ANOVA with repeated measures, Newman Keuls post-hoc analyses). This exercise-induced autolysis was attributed to myofibrillar bound calpain-3 since neither the amount of calpain-3 nor the proportion autolyzed were significantly changed in either 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. |
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Authors:
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Robyn M Murphy; Kristian Vissing; Heidy Latchman; Cedric Lamboley; Michael John McKenna; Kristian Overgaard; Graham D Lamb |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-11 |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: - ISSN: 1522-1601 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1La Trobe University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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