Journal de protéomique et bioinformatique
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Comparative Proteomics for Studying Muscular Dystrophy: Intrinsic Biological and Analytical Issues Associated with the Systematic Utilization of Tissue Specimens

Ashling Holland and Kay Ohlendieck

Over the past decade, mass spectrometry-based proteomics has been instrumental for the detailed elucidation of pathobiochemical mechanisms involved in major neuromuscular diseases. Although the identification of musclederived proteins in biofluids is the main focus of diagnostic biomarker research, the large-scale proteomic analysis of pathological muscle tissue is of central importance for furthering our general understanding of the dysregulation that underlies complex muscle diseases. Here, we discuss intrinsic biological issues and bioanalytical difficulties that are generally associated with comparative muscle tissue proteomics. The systematic utilization of cellular mixtures or whole tissue specimens as starting material for studying neuromuscular pathology is seriously complicated by the cellular heterogeneity and physiological plasticity of contractile tissues. The comprehensive biochemical analysis of the skeletal muscle proteome is often hampered by the wide dynamic expression range of proteins, the greatly differing physicochemical properties of dissimilar muscle protein species and the potential cross-contamination of samples by highly abundant proteins. Thus, neither gel electrophoretic methodology nor liquid chromatography, is capable of appropriately separating all constituents of the skeletal muscle proteome. However, the application of advanced extraction strategies, the usage of subcellular fractionation protocols to reduce sample complexity and the affinity purification of distinct protein fractions prior to mass spectrometric analysis promises to overcome some of the inherent problems associated with muscle tissue proteomics.