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    Reduced expression of regucalcin in young and aged mdx diaphragm indicates abnormal cytosolic calcium handling in dystrophin-deficient muscle


    Doran, Philip and Dowling, Paul and Donoghue, Pamela and Buffini, Maria and Ohlendieck, Kay (2006) Reduced expression of regucalcin in young and aged mdx diaphragm indicates abnormal cytosolic calcium handling in dystrophin-deficient muscle. Biochimica et Biophysica Acta - Proteins and Proteomics, 1764 (4). pp. 773-785. ISSN 1570-9639

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    Abstract

    The cytosolic Ca2+ -binding protein regucalcin is involved in intracellular signaling and present in high abundance in the liver. Here, we could show by comparative mass spectrometry-based proteomics screening of normal versus dystrophic fibres that regucalcin of 33.9 kDa and pI5.2 also exists in diaphragm muscle. Since the expression of sarcolemmal Ca2+ -leak channels and luminal Ca2+ -binding elements is altered in dystrophin-deficient muscle, we initiated this study in order to determine whether additional soluble muscle proteins involved in Ca2+ -handling are affected in muscular dystrophy. Following separation by two-dimensional gel electrophoresis, the spot pattern of the normal versus the mdx diaphragm muscle proteome was evaluated by densitometry. The expression levels of 20 major protein spots were shown to change and their identity determined by mass spectrometry. A 2-fold reduction of regucalcin in mdx diaphragm, as well as in dystrophic limb muscle and heart, was confirmed by immunoblotting in both young and aged mdx mice. The results from our proteomics analysis of dystrophic diaphragm support the concept that abnormal Ca2+ -handling is involved in x-linked muscular dystrophy. The reduction in key Ca2+ -handling proteins may result in an insufficient maintenance of Ca2+ -homeostasis and an abnormal regulation of Ca2+ -dependent enzymes resulting in disturbed intracellular signaling mechanisms in dystrophinopathies.

    Item Type: Article
    Keywords: mdx diaphragm; Calcium homeostasis; Regucalcin; Muscle proteomics; Muscular dystrophy;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7356
    Identification Number: https://doi.org/10.1016/j.bbapap.2006.01.007
    Depositing User: Paul Dowling
    Date Deposited: 18 Aug 2016 15:22
    Journal or Publication Title: Biochimica et Biophysica Acta - Proteins and Proteomics
    Publisher: Elsevier
    Refereed: Yes
    Funders: Science Foundation Ireland (SFI), Muscular Dystrophy Ireland, European Commission, Health Research Board (HRB)
    URI:

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