Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis
Copyright policy )Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis
Glycogen storage disease type V (GSDV, McArdle disease) is a rare genetic myopathy caused by deficiency of the muscle isoform of glycogen phosphorylase (PYGM). This results in a block in the use of muscle glycogen as an energetic substrate, with subsequent exercise intolerance. The pathobiology of GSDV is still not fully understood, especially with regard to some features such as persistent muscle damage (i.e., even without prior exercise). We aimed at identifying potential muscle protein biomarkers of GSDV by analyzing the muscle proteome and the molecular networks associated with muscle dysfunction in these patients. Muscle biopsies from eight patients and eight healthy controls showing none of the features of McArdle disease, such as frequent contractures and persistent muscle damage, were studied by quantitative protein expression using isobaric tags for relative and absolute quantitation (iTRAQ) followed by artificial neuronal networks (ANNs) and topology analysis. Protein candidate validation was performed by Western blot. Several proteins predominantly involved in the process of muscle contraction and/or calcium homeostasis, such as myosin, sarcoplasmic/endoplasmic reticulum calcium ATPase 1, tropomyosin alpha-1 chain, troponin isoforms, and alpha-actinin-3, showed significantly lower expression levels in the muscle of GSDV patients. These proteins could be potential biomarkers of the persistent muscle damage in the absence of prior exertion reported in GSDV patients. Further studies are needed to elucidate the molecular mechanisms by which PYGM controls the expression of these proteins.
Proteomics, Other subheadings::Other subheadings::Other subheadings::/genetics, McArdle disease, Enfermedad del almacenamiento de glucógeno tipo V, Múscul estriat - Patogènesi, Proteome, Enfermedad cardiovascular, 610, Skeletal muscle, ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::trastornos congénitos del metabolismo de los carbohidratos::enfermedad por almacenamiento de glucógeno::enfermedad por almacenamiento de glucógeno tipo V, Genética humana, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteoma, DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Carbohydrate Metabolism, Inborn Errors::Glycogen Storage Disease::Glycogen Storage Disease Type V, Article, PYGM, CHEMICALS AND DRUGS::Biological Factors::Biomarkers, proteomics, Otros calificadores::Otros calificadores::Otros calificadores::/genética, 616, myophosphorylase, Humans, Protein Isoforms, COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores, skeletal muscle, Muscle, Skeletal, Metabolic myopathy, PYGM; myophosphorylase; proteomics; McArdle disease; GSDV; iTRAQ; skeletal muscle; metabolic myopathy; protein biomarkers, Metabolismo, Itraq, protein biomarkers, Glicogen, metabolic myopathy, Myophosphorylase, iTRAQ, GSDV, Protein biomarkers, Marcadors bioquímics, Glycogen Storage Disease Type V, Metabolisme, Errors congènits del, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Proteome, Biomarkers, Glycogen
Proteomics, Other subheadings::Other subheadings::Other subheadings::/genetics, McArdle disease, Enfermedad del almacenamiento de glucógeno tipo V, Múscul estriat - Patogènesi, Proteome, Enfermedad cardiovascular, 610, Skeletal muscle, ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::trastornos congénitos del metabolismo de los carbohidratos::enfermedad por almacenamiento de glucógeno::enfermedad por almacenamiento de glucógeno tipo V, Genética humana, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteoma, DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Carbohydrate Metabolism, Inborn Errors::Glycogen Storage Disease::Glycogen Storage Disease Type V, Article, PYGM, CHEMICALS AND DRUGS::Biological Factors::Biomarkers, proteomics, Otros calificadores::Otros calificadores::Otros calificadores::/genética, 616, myophosphorylase, Humans, Protein Isoforms, COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores, skeletal muscle, Muscle, Skeletal, Metabolic myopathy, PYGM; myophosphorylase; proteomics; McArdle disease; GSDV; iTRAQ; skeletal muscle; metabolic myopathy; protein biomarkers, Metabolismo, Itraq, protein biomarkers, Glicogen, metabolic myopathy, Myophosphorylase, iTRAQ, GSDV, Protein biomarkers, Marcadors bioquímics, Glycogen Storage Disease Type V, Metabolisme, Errors congènits del, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Proteome, Biomarkers, Glycogen
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