Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis
Por:
Garcia-Consuegra, I, Asensio-Pena, S, Garrido-Moraga, R, Pinos, T, Dominguez-Gonzalez, C, Santalla, A, Nogales-Gadea, G, Serrano-Lorenzo, P, Andreu, AL, Arenas, J, Zugaza, JL, Lucia, A and Martin, MA
Publicada:
1 may 2022
Resumen:
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.
Filiaciones:
Garcia-Consuegra, I:
Hosp Octubre Hlth Res Inst, Mitochondrial & Neuromuscular Disorders Grp, Madrid 28041, Spain
Ctr Invest Biomed Red Enfermedades Raras C, Madrid 28029, Spain
Asensio-Pena, S:
Hosp Octubre Hlth Res Inst, Mitochondrial & Neuromuscular Disorders Grp, Madrid 28041, Spain
Garrido-Moraga, R:
Hosp Octubre Hlth Res Inst, Mitochondrial & Neuromuscular Disorders Grp, Madrid 28041, Spain
Pinos, T:
Ctr Invest Biomed Red Enfermedades Raras C, Madrid 28029, Spain
Univ Autonoma Barcelona, Vall Hebron Inst Recerca, Mitochondrial & Neuromuscular Disorders Unit, Barcelona 08193, Spain
Dominguez-Gonzalez, C:
Hosp Octubre Hlth Res Inst, Mitochondrial & Neuromuscular Disorders Grp, Madrid 28041, Spain
Ctr Invest Biomed Red Enfermedades Raras C, Madrid 28029, Spain
Santalla, A:
Univ Pablo Olavide, Dept Comp & Sport Sci, Seville 41013, Spain
:
Univ Autonoma Barcelona, Inst Invest Ciencies Salut Germans Trias P, Dept Neurosci, Grup Recerca Malalties Neuromusculars Neuropediat, Barcelona 08916, Spain
Serrano-Lorenzo, P:
Hosp Octubre Hlth Res Inst, Mitochondrial & Neuromuscular Disorders Grp, Madrid 28041, Spain
Ctr Invest Biomed Red Enfermedades Raras C, Madrid 28029, Spain
Andreu, AL:
EATRIS, European Infrastruct Translat Med, NL-1019 Amsterdam, Netherlands
Arenas, J:
Hosp Octubre Hlth Res Inst, Mitochondrial & Neuromuscular Disorders Grp, Madrid 28041, Spain
Ctr Invest Biomed Red Enfermedades Raras C, Madrid 28029, Spain
Zugaza, JL:
Sci Pk UPV EHU, Achucarro Basque Ctr Neurosci, Leioa 48940, Spain
Univ Basque Country, Fac Sci & Technol, Dept Genet Phys Anthropol & Anim Physiol, Leioa 48940, Spain
Basque Fdn Sci, Ikerbasque, Plaza Euskadi 5, Bilbao 48009, Spain
Lucia, A:
Hosp Octubre Hlth Res Inst, Mitochondrial & Neuromuscular Disorders Grp, Madrid 28041, Spain
Univ Europea Madrid, Fac Sport Sci, Madrid 28670, Spain
Martin, MA:
Hosp Octubre Hlth Res Inst, Mitochondrial & Neuromuscular Disorders Grp, Madrid 28041, Spain
Ctr Invest Biomed Red Enfermedades Raras C, Madrid 28029, Spain
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