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Am J Physiol Cell Physiol. 2009 Feb;296(2):C363-71. doi: 10.1152/ajpcell.00497.2008. Epub 2008 Dec 24.

Calpain-1 is required for hydrogen peroxide-induced myotube atrophy.

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  • 1Dept. of Applied Physiology and Kinesiology, Univ. of Florida, Rm. 25 Florida Gym, Gainesville, FL 32611, USA. joseph.mcclung@duke.edu

Abstract

Recent reports suggest numerous roles for cysteine proteases in the progression of skeletal muscle atrophy due to disuse or disease. Nonetheless, a specific requirement for these proteases in the progression of skeletal muscle atrophy has not been demonstrated. Therefore, this investigation determined whether calpains or caspase-3 is required for oxidant-induced C2C12 myotube atrophy. We demonstrate that exposure to hydrogen peroxide (25 microM H2O2) induces myotube oxidative damage and atrophy, with no evidence of cell death. Twenty-four hours of exposure to H2O2 significantly reduced both myotube diameter and the abundance of numerous proteins, including myosin (-81%), alpha-actinin (-40%), desmin (-79%), talin (-37%), and troponin I (-80%). Myotube atrophy was also characterized by increased cleavage of the cysteine protease substrate alphaII-spectrin following 4 h and 24 h of H2O2 treatment. This degradation was blocked by administration of the protease inhibitor leupeptin (10 microM). Using small interfering RNA transfection of mature myotubes against the specific proteases calpain-1, calpain-2, and caspase-3, we demonstrated that calpain-1 is required for H2O2-induced myotube atrophy. Collectively, our data provide the first evidence for an absolute requirement for calpain-1 in the development of skeletal muscle myotube atrophy in response to oxidant-induced cellular stress.

PMID:
19109522
[PubMed - indexed for MEDLINE]
PMCID:
PMC2643855
Free PMC Article
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