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Calpain-1 is required for hydrogen peroxide-induced myotube atrophy
Journal article   Open access   Peer reviewed

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

J. M. McClung, A. R. Judge, E. E. Talbert and S. K. Powers
American Journal of Physiology: Cell Physiology, Vol.296(2), pp.C363-C371
02/01/2009
DOI: 10.1152/ajpcell.00497.2008
PMCID: PMC2643855
PMID: 19109522
url
https://doi.org/10.1152/ajpcell.00497.2008View
Published (Version of record) Open Access

Abstract

McClung JM, Judge AR, Talbert EE, Powers SK. Calpain-1 is required for hydrogen peroxide-induced myotube atrophy. Am J Physiol Cell Physiol 296: C363-C371, 2009. First published December 24, 2008; doi:10.1152/ajpcell.00497.2008.-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 mu M 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 alpha II-spectrin following 4 h and 24 h of H2O2 treatment. This degradation was blocked by administration of the protease inhibitor leupeptin (10 mu M). 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.
Cell Biology Physiology Life Sciences & Biomedicine Science & Technology

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