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Proteomics identification of differentially expressed proteins in the muscle of dysferlin myopathy patients
Author(s) -
De la Torre Carolina,
Illa Isabel,
Faulkner Georgine,
Soria Laura,
RoblesCedeño Rene,
DominguezPerles Raul,
De Luoemí,
Gallardo Eduard
Publication year - 2009
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200800087
Subject(s) - dysferlin , limb girdle muscular dystrophy , myopathy , muscular dystrophy , skeletal muscle , biology , itga7 , facioscapulohumeral muscular dystrophy , phenotype , sarcomere , pathology , medicine , myocyte , endocrinology , genetics , gene
The muscular dystrophies are a large and heterogeneous group of neuromuscular disorders that can be classified according to the mode of inheritance, the clinical phenotype and the molecular defect. To better understand the pathological mechanisms of dysferlin myopathy we compared the protein‐expression pattern in the muscle biopsies of six patients with this disease with six patients with limb girdle muscular dystrophy 2A, five with facioscapulohumeral dystrophy and six normal control subjects. To investigate differences in the expression levels of skeletal muscle proteins we used 2‐DE and MS. Western blot or immunohistochemistry confirmed relevant results. The study showed specific increase expression of proteins involved in fast‐to‐slow fiber type conversion (ankyrin repeat protein 2), type I predominance (phosphorylated forms of slow troponin T), sarcomere stabilization (actinin‐associated LIM protein), protein ubiquitination (TRIM 72) and skeletal muscle differentiation (Rho‐GDP‐dissociation inhibitor ly‐GDI) in dysferlin myopathy. As anticipated, we also found differential expression of proteins common to all the muscular dystrophies studied. This comparative proteomic analysis suggests that in dysferlin myopathy (i) the type I fiber predominance is an active process of fiber type conversion rather than a selective loss of type II fibers and (ii) the dysregulation of proteins involved in muscle differentiation further confirms the role of dysferlin in this process.