Dataset Information

The Human Skeletal Muscle Proteome Project: a reappraisal of the current literature.

ABSTRACT: Skeletal muscle is a large organ that accounts for up to half the total mass of the human body. A progressive decline in muscle mass and strength occurs with ageing and in some individuals configures the syndrome of 'sarcopenia', a condition that impairs mobility, challenges autonomy, and is a risk factor for mortality. The mechanisms leading to sarcopenia as well as myopathies are still little understood. The Human Skeletal Muscle Proteome Project was initiated with the aim to characterize muscle proteins and how they change with ageing and disease. We conducted an extensive review of the literature and analysed publically available protein databases. A systematic search of peer-reviewed studies was performed using PubMed. Search terms included 'human', 'skeletal muscle', 'proteome', 'proteomic(s)', and 'mass spectrometry', 'liquid chromatography-mass spectrometry (LC-MS/MS)'. A catalogue of 5431 non-redundant muscle proteins identified by mass spectrometry-based proteomics from 38 peer-reviewed scientific publications from 2002 to November 2015 was created. We also developed a nosology system for the classification of muscle proteins based on localization and function. Such inventory of proteins should serve as a useful background reference for future research on changes in muscle proteome assessed by quantitative mass spectrometry-based proteomic approaches that occur with ageing and diseases. This classification and compilation of the human skeletal muscle proteome can be used for the identification and quantification of proteins in skeletal muscle to discover new mechanisms for sarcopenia and specific muscle diseases that can be targeted for the prevention and treatment.

SUBMITTER: Gonzalez-Freire M

PROVIDER: S-EPMC5326819 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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The Human Skeletal Muscle Proteome Project: a reappraisal of the current literature.

Gonzalez-Freire Marta M Semba Richard D RD Ubaida-Mohien Ceereena C Fabbri Elisa E Scalzo Paul P Højlund Kurt K Dufresne Craig C Lyashkov Alexey A Ferrucci Luigi L

Journal of cachexia, sarcopenia and muscle 20160803 1

Skeletal muscle is a large organ that accounts for up to half the total mass of the human body. A progressive decline in muscle mass and strength occurs with ageing and in some individuals configures the syndrome of 'sarcopenia', a condition that impairs mobility, challenges autonomy, and is a risk factor for mortality. The mechanisms leading to sarcopenia as well as myopathies are still little understood. The Human Skeletal Muscle Proteome Project was initiated with the aim to characterize musc ...[more]

PMID: 27897395

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Project description:Skeletal muscle is one of the largest tissues in the human body. Changes in mRNA and protein abundance in this tissue are central to a large number of metabolic and other disorders, including, commonly, insulin resistance. Proteomic and microarray analyses are important approaches for gaining insight into the molecular and biochemical basis for normal and pathophysiological conditions. With the use of vastus lateralis muscle obtained from two groups of healthy, nonobese subjects, we performed a detailed comparison of the muscle proteome, obtained by HPLC-ESI-MS/MS, with the muscle transcriptome, obtained using oligonucleotide microarrays. HPLC-ESI-MS/MS analysis identified 507 unique proteins as present in four out of six subjects, while 5193 distinct transcripts were called present by oligonucleotide microarrays from four out of six subjects. The majority of the proteins identified by mass spectrometry also had their corresponding transcripts detected by microarray analysis, although 73 proteins were only identified in the proteomic analysis. Reflecting the high abundance of mitochondria in skeletal muscle, 30% of proteins detected were attributed to the mitochondrion, as compared to only 9% of transcripts. On the basis of Gene Ontology annotations, proteins assigned to mitochondrial inner membrane, mitochondrial envelope, structural molecule activity, electron transport, as well as generation of precursor metabolites and energy, had more corresponding transcripts detected than would be expected by chance. On the contrary, proteins assigned to Golgi apparatus, extracellular region, lyase activity, kinase activity, and protein modification process had fewer corresponding transcripts detected than would be expected by chance. In conclusion, these results provide the first global comparison of the human skeletal muscle proteome and transcriptome to date. These data show that a combination of proteomic and transcriptic analyses will provide data that can be used to test hypotheses regarding the pathogenesis of muscle disorders as well as to generate observational data that can be used to form novel hypotheses.

Project description:Introduction: Both cancer and cancer associated therapies (CAT; including chemotherapy or concurrent chemoradiation) disrupt cellular metabolism throughout the body, including the regulation of skeletal muscle mass and function. Adjunct testosterone therapy during standard of care chemotherapy and chemoradiation modulates CAT-induced dysregulation of skeletal muscle metabolism and protects lean body mass during CAT. However, the extent to which the skeletal muscle proteome is altered under these therapeutic conditions is unknown. Objective: We probed the skeletal muscle proteome of cancer patients as an ancillary analysis following a randomized, double-blind, placebo-controlled phase II trial investigating the effect of adjunct testosterone on body composition in men and women with advanced cancers undergoing CAT. Methods: Men and women diagnosed with late stage (≥IIB) or recurrent head and neck or cervical cancer who were scheduled to receive standard of care CAT were administered an adjunct 7 weeks treatment of weekly intramuscular injections of either 100 mg testosterone (CAT+T, n = 7; 2M/5F) or placebo/saline (CAT+P, n = 6; 4M/2F). Biopsies were performed on the vastus lateralis before (PRE) and after (POST) the 7 weeks treatment. Extracted proteins were separated with 2-dimensional gel electrophoresis (2DE), and subjected to analyses of total protein abundance, phosphorylation and S-nitrosylation. Proteoforms showing significant 1.5 fold differences (t-test p ≤ 0.05) between PRE and POST timepoints were identified by mass spectroscopy (MS), and lists of altered proteins were subjected to Gene Set Enrichment Analysis (GSEA) to identify affected pathways. Results: A total of 756 distinct protein spots were identified. Of those spots, 102 were found to be altered in terms of abundance, phosphorylation, or S-nitrosylation, and identified by mass spectroscopy analysis to represent 58 unique proteins. Among the biological processes and pathways identified, CAT+P predominantly impacted metabolic processes, cell assembly, oxygen transport, and apoptotic signaling, while CAT+T impacted transcription regulation, muscle differentiation, muscle development, and contraction. Conclusion: Cancer and CAT significantly altered the skeletal muscle proteome in a manner suggestive of loss of structural integrity, reduced contractile function, and disrupted metabolism. Proteomic analysis suggests that the addition of adjunct testosterone minimized the structural and contractile influence of cancer and its associated therapies.

Dataset Information

The Human Skeletal Muscle Proteome Project: a reappraisal of the current literature.

Publications

The Human Skeletal Muscle Proteome Project: a reappraisal of the current literature.

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