Proteomic profiling of animal models mimicking skeletal muscle disorders

Abstract

Over the last few decades of biomedical research, animal models of neuromuscular diseases have been widely used for determining pathological mechanisms and for testing new therapeutic strategies. With the emergence of high-throughput proteomics technology, the identification of novel protein factors involved in disease processes has been decisively improved. This review outlines the usefulness of the proteomic profiling of animal disease models for the discovery of new reliable biomarkers, for the optimization of diagnostic procedures and the development of new treatment options for skeletal muscle disorders. Since inbred animal strains show genetically much less interindividual differences as compared to human patients, considerably lower experimental repeats are capable of producing meaningful proteomic data. Thus, animal model proteomics can be conveniently employed for both studying basic mechanisms of molecular pathogenesis and the effects of drugs, genetic modifications or cell-based therapies on disease progression. Based on the results from comparative animal proteomics, a more informed decision on the design of clinical proteomics studies could be reached. Since no one animal model represents a perfect pathobiochemical replica of all of the symptoms seen in complex human disorders, the proteomic screening of novel animal models can also be employed for swift and enhanced protein biochemical phenotyping.

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

“…This can be advantageous for the identification of lowabundance signature molecules. With respect to muscle proteomics, the mass spectrometry-based profiling of crude muscle extracts has decisively advanced basic and applied myology [13,37,38], but a major limitation of current proteomic platforms is their limited dynamic range for resolving complex protein complements. Crude extract proteomics is therefore unable to reveal the complete proteome complexity of whole skeletal muscles.…”

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age

“…As recently reviewed by Vijg and Campisi (2008), sarcopenia-related muscle weakness represents a conserved aging phenotype and affects a diverse range of species, including Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Rattus rattus and Homo sapiens. Since cross-sectional studies with differently aged human muscle specimens have to be often interpreted with caution due to fundamental differences in general lifestyle, activity patterns and food habits of examined individuals (Proctor et al, 1999;Melton et al, 2000;Lindle et al, 1997), initial model studies with inbred animal strains can give crucial data for the design of more advanced studies in human populations (Doran et al, 2007b). Therefore, the alternative analysis of aged animals with a suitable phenotype plays a vital role in modern biogerontology.…”

“…The activity level of the younger rat population was enhanced as compared to the older cohort. Both human and rat muscles share common age-related changes (Edstrom et al, 2007), making 26-month-old Wistar rat muscle a suitable model system to study age-dependent adaptations in sarcopenia (Doran et al, 2007b). Rat muscle aging is associated with fibre degeneration, altered fibre type size, changed fibre proportions, the incomplete recruitment of distinct fibre groupings and overall contractile weakness (Larsson and Edstrom, 1986;Alnaqeeb and Goldspink, 1987;Edstrom and Larsson, 1987;Larsson et al, 1991;Cutlip et al, 2007).…”

Lectin-based proteomic profiling of aged skeletal muscle: Decreased pyruvate kinase isozyme M1 exhibits drastically increased levels of N-glycosylation

“…As an established tissue model of sarcopenia, 30-month-old rat gastrocnemius muscle was used (Edstrom et al, 2007;Doran et al, 2007a). WGA labeling revealed an altered glycosylation in the major metabolic muscle protein pyruvate kinase and a concomitant reduction in enzyme activity.…”