Identification of Potential Muscle Biomarkers in McArdle Disease : Insights from Muscle Proteome Analysis
García-Consuegra, Inés (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Asensio-Peña, Sara (Instituto de Investigación Sanitaria Hospital 12 de Octubre (Madrid))
Garrido-Moraga, Rocío (Instituto de Investigación Sanitaria Hospital 12 de Octubre (Madrid))
Pinós Figueras, Tomàs (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Domínguez-González, C (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Santalla, Alfredo (Universidad Pablo de Olavide)
Nogales, Gisela (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Serrano-Lorenzo, Pablo (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Andreu Périz, Antoni Lluís (European Infrastructure for Translational Medicine (Amsterdam, Holanda))
Arenas, Joaquín (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Zugaza, José L. (Basque Foundation for Science (Bilbao, País Basc))
Lucia, Alejandro (Universidad Europea de Madrid)
Martín, Miguel Angel (Centro de Investigación Biomédica en Red de Enfermedades Raras)

Data:	2022
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI17/02052 Instituto de Salud Carlos III PI19/01313 Instituto de Salud Carlos III CPII19/00021
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	PYGM ; Myophosphorylase ; Proteomics ; McArdle disease ; GSDV ; Itraq ; Skeletal muscle ; Metabolic myopathy ; Protein biomarkers
Publicat a:	International journal of molecular sciences, Vol. 23 (april 2022) , ISSN 1422-0067

DOI: 10.3390/ijms23094650
PMID: 35563042

18 p, 814.2 KB

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