Regulation of the calpain and ubiquitin-proteasome systems in a canine model of muscular dystrophy

Authors

  • Kristine M. Wadosky BS,

    1. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    2. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Luge Li BS,

    1. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    2. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Jessica E. Rodríguez BS,

    1. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    2. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Jin-na Min PhD,

    1. McAllister Heart Institute, University of North Carolina, Medical Biomolecular Research Building, 103 Mason Farm Road, Chapel Hill, North Carolina 27599-7525, USA
    2. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Dan Bogan MS,

    1. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    2. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Jason Gonzalez BS,

    1. Department of Exercise and Sports Science, University of North Carolina, Chapel Hill, North Carolina, USA
    2. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Cam Patterson MD,

    1. McAllister Heart Institute, University of North Carolina, Medical Biomolecular Research Building, 103 Mason Farm Road, Chapel Hill, North Carolina 27599-7525, USA
    2. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Joe N. Kornegay DVM, PhD,

    1. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    2. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Monte Willis MD, PhD

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    2. McAllister Heart Institute, University of North Carolina, Medical Biomolecular Research Building, 103 Mason Farm Road, Chapel Hill, North Carolina 27599-7525, USA
    3. Department of Medicine and Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
    • Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
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Abstract

Introduction: Previous studies have tested the hypothesis that calpain and/or proteasome inhibition is beneficial in Duchenne muscular dystrophy, based largely on evidence that calpain and proteasome activities are enhanced in the mdx mouse. Methods: mRNA expression of ubiquitin-proteasome and calpain system components were determined using real-time polymerase chain reaction in skeletal muscle and heart in the golden retriever muscular dystrophy model. Similarly, calpain 1 and 2 and proteasome activities were determined using fluorometric activity assays. Results: We found that less than half of the muscles tested had increases in proteasome activity, and only half had increased calpain activity. In addition, transcriptional regulation of the ubiquitin-proteasome system was most pronounced in the heart, where numerous components were significantly decreased. Conclusion: This study illustrates the diversity of expression and activities of the ubiquitin-proteasome and calpain systems, which may lead to unexpected consequences in response to pharmacological inhibition. Muscle Nerve, 2011

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