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    Proteomic profiling of cardiomyopathic tissue from the aged mdx model of Duchenne muscular dystrophy reveals a drastic decrease in laminin, nidogen and annexin


    Holland, Ashling and Dowling, Paul and Zweyer, Margit and Swandulla, Dieter and Henry, Michael and Clynes, Martin and Ohlendieck, Kay (2013) Proteomic profiling of cardiomyopathic tissue from the aged mdx model of Duchenne muscular dystrophy reveals a drastic decrease in laminin, nidogen and annexin. Proteomics, 13 (15). pp. 2312-2323. ISSN 1615-9853

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    Abstract

    The majority of patients afflicted with Duchenne muscular dystrophy develop cardiomyopathic complications, warranting large-scale proteomic studies of global cardiac changes for the identification of new protein markers of dystrophinopathy. The aged heart from the X-linked dystrophic mdx mouse has been shown to exhibit distinct pathological aspects of cardiomyopathy. In order to establish age-related alterations in the proteome of dystrophin-deficient hearts, cardiomyopathic tissue from young versus aged mdx mice was examined by label-free LC-MS/MS. Significant age-dependent alterations were established for 67 proteins, of which 28 proteins were shown to exhibit a lower abundance and 39 proteins were found to be increased in their expression levels. Drastic changes were demonstrated for 17 proteins, including increases in Ig chains and transferrin, and drastic decreases in laminin, nidogen and annexin. An immunblotting survey of young and old wild-type versus mdx hearts confirmed these proteomic findings and illustrated the effects of natural aging versus dystrophin deficiency. These proteome-wide alterations suggest a disintegration of the basal lamina structure and cytoskeletal network in dystrophin-deficient cardiac fibres, increased levels of antibodies in a potential autoimmune reaction of the degenerating heart, compensatory binding of excess iron and a general perturbation of metabolic pathways in dystrophy-associated cardiomyopathy.

    Item Type: Article
    Additional Information: The definitive published version of this article is available at DOI: 10.1002/pmic.201200578
    Keywords: Animal proteomics; Annexin; Cardiomyopathy; Laminin; Muscular dystrophy; Nidogen;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 6925
    Identification Number: https://doi.org/10.1002/pmic.201200578
    Depositing User: Paul Dowling
    Date Deposited: 26 Jan 2016 17:33
    Journal or Publication Title: Proteomics
    Publisher: Wiley
    Refereed: Yes
    Funders: Muscular Dystrophy Ireland, Higher Education Authority (HEA)
    URI:

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