Diversity of human skeletal muscle in health and disease: Contribution of proteomics

Gelfi, Cecilia; Vasso, Michele; Cerretelli, Paolo

doi:10.1016/j.jprot.2011.02.028

Cited by 62 publications

(69 citation statements)

References 142 publications

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“…Approximately 750 to 850 proteins were identified and quantified in the gastrocnemius muscle. These numbers are similar to those previously reported in other skeletal muscle proteome studies (29,30). However, these numbers are lower than those from a recent study in which a highly sensitive mass spectrometer was used on samples that were subjected to extensive fractionation (31).…”

Section: Mitochondria and Metabolic Enzymes Are Affected In Dystrophisupporting

confidence: 87%

Identification of Disease Specific Pathways Using in Vivo SILAC Proteomics in Dystrophin Deficient mdx Mouse

Rayavarapu

Coley

Çakır

et al. 2013

Molecular & Cellular Proteomics

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Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by a mutation in the dystrophin gene. DMD is characterized by progressive weakness of skeletal, cardiac, and respiratory muscles. The molecular mechanisms underlying dystrophy-associated muscle weakness and damage are not well understood. Quantitative proteomics techniques could help to identify disease-specific pathways. Recent advances in the in vivo labeling strategies such as stable isotope labeling in mouse (SILAC mouse) with 13 C 6 -lysine or stable isotope labeling in mammals (SILAM) with 15 N have enabled accurate quantitative analysis of the proteomes of whole organs and tissues as a function of disease. Here we describe the use of the SILAC mouse strategy to define the underlying pathological mechanisms in dystrophindeficient skeletal muscle. Differential SILAC proteome profiling was performed on the gastrocnemius muscles of 3-week-old (early stage) dystrophin-deficient mdx mice and wild-type (normal) mice. The generated data were further confirmed in an independent set of mdx and normal mice using a SILAC spike-in strategy. A total of 789 proteins were quantified; of these, 73 were found to be significantly altered between mdx and normal mice (p < 0.05). Bioinformatics analyses using Ingenuity Pathway software established that the integrin-linked kinase pathway, actin cytoskeleton signaling, mitochondrial energy metabolism, and calcium homeostasis are the pathways initially affected in dystrophin-deficient muscle at early stages of pathogenesis. The key proteins involved in these pathways were validated by means of immunoblotting and immunohistochemistry in independent sets of mdx mice and in human DMD muscle biopsies. The specific involvement of these molecular networks early in dystrophic pathology makes them potential therapeutic targets. In sum, our findings indicate that SILAC mouse strategy has uncovered previously unidentified pathological pathways in mouse models of human skeletal muscle disease. Molecular & Cellular

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Section: Mitochondria and Metabolic Enzymes Are Affected In Dystrophisupporting

confidence: 87%

Identification of Disease Specific Pathways Using in Vivo SILAC Proteomics in Dystrophin Deficient mdx Mouse

Rayavarapu

Coley

Çakır

et al. 2013

Molecular & Cellular Proteomics

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“…Since the proteome -the set of proteins present in a tissue -is the result of gene expression and epigenetic influences, the study of protein abundance in muscle may provide new insights into the molecular processes that lead to metabolic dysfunction in situations where the concentrations of circulating androgens are altered, an issue that has not been addressed in previous proteomic studies of muscle in insulin resistance-related disorders (8,9,10).…”

Section: Introductionmentioning

confidence: 99%

A nontargeted study of muscle proteome in severely obese women with androgen excess compared with severely obese men and nonhyperandrogenic women

Insenser

Montes-Nieto

Martínez‐García

et al. 2016

European Journal of Endocrinology

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Objective: Androgen excess in women is frequently associated with muscle insulin resistance, especially in obese women with polycystic ovary syndrome. However, whether this is a primary event or the result of indirect mechanisms is currently debated. Design: This is an observational study. Methods: We obtained skeletal muscle biopsies during bariatric surgery from severely obese men (nZ6) and women with (nZ5) or without (nZ5) androgen excess. We used two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight mass spectrometry to identify muscle proteins showing differences in abundance between the groups of obese subjects. Results: Women with hyperandrogenism presented the lowest abundances of glycogen phosphorylase, pyruvate kinase, b-enolase, glycerol-3-phosphate dehydrogenase, creatine kinase M-type, and desmin, whereas the abundances of these molecules were similar in control women and men. Conclusion: According to our nontargeted proteomic approach, women with hyperandrogenism show a specific alteration of the skeletal muscle proteome that could contribute to their insulin resistance. Because men do not show similar results, this alteration does not appear to be the direct effect on muscle of androgen excess, but rather the consequence of indirect mechanisms that merit further studies.

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“…14,15 Large-scale proteomic studies on rodent skeletal muscle cell lines have also provided invaluable information on the global changes affecting the proteome during in vitro muscle formation. 16−19 Although mouse C2C12 and rat L6 are widely used experimental models to study myogenesis in vitro, these rodent cell lines, by nature of their immortality, may not represent bona f ide satellite cells.…”

Section: ■ Introductionmentioning

confidence: 99%

Cellular Proteome Dynamics during Differentiation of Human Primary Myoblasts

et al. 2015

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Muscle stem cells, or satellite cells, play an important role in the maintenance and repair of muscle tissue and have the capacity to proliferate and differentiate in response to physiological or environmental changes. Although they have been extensively studied, the key regulatory steps and the complex temporal protein dynamics accompanying the differentiation of primary human muscle cells remain poorly understood. Here, we demonstrate the advantages of applying a MS-based quantitative approach, stable isotope labeling by amino acids in cell culture (SILAC), for studying human myogenesis in vitro and characterize the fine-tuned changes in protein expression underlying the dramatic phenotypic conversion of primary mononucleated human muscle cells during in vitro differentiation to form multinucleated myotubes. Using an exclusively optimized triple encoding SILAC procedure, we generated dynamic expression profiles during the course of myogenic differentiation and quantified 2240 proteins, 243 of which were regulated. These changes in protein expression occurred in sequential waves and underlined vast reprogramming in key processes governing cell fate decisions, i.e., cell cycle withdrawal, RNA metabolism, cell adhesion, proteolysis, and cytoskeletal organization. In silico transcription factor target analysis demonstrated that the observed dynamic changes in the proteome could be attributed to a cascade of transcriptional events involving key myogenic regulatory factors as well as additional regulators not yet known to act on muscle differentiation. In addition, we created of a dynamic map of the developing myofibril, providing valuable insights into the formation and maturation of the contractile apparatus in vitro. Finally, our SILAC-based quantitative approach offered the possibility to follow the expression profiles of several muscle disease-associated proteins simultaneously and therefore could be a valuable resource for future studies investigating pathogenesis of degenerative muscle disorders as well as assessing new therapeutic strategies.

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Diversity of human skeletal muscle in health and disease: Contribution of proteomics

Abstract: Muscle represents a large fraction of the human body mass. It is an extremely heterogeneous tissue featuring in its contractile structure various proportions of heavy-

Cited by 62 publications

References 142 publications

Identification of Disease Specific Pathways Using in Vivo SILAC Proteomics in Dystrophin Deficient mdx Mouse

Identification of Disease Specific Pathways Using in Vivo SILAC Proteomics in Dystrophin Deficient mdx Mouse

A nontargeted study of muscle proteome in severely obese women with androgen excess compared with severely obese men and nonhyperandrogenic women

Cellular Proteome Dynamics during Differentiation of Human Primary Myoblasts

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