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Expression of glycogen phosphorylase isoforms in cultured muscle from patients with McArdle's disease carrying the p.R771PfsX33 PYGM mutation

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dc.contributor.author Nogales-Gadea, Gisela spa
dc.contributor.author Mormeneo, Emma spa
dc.contributor.author García-Consuegra, Inés spa
dc.contributor.author Rubio, Juan Carlos spa
dc.contributor.author Orozco, Anna spa
dc.contributor.author Arenas, Joaquín spa
dc.contributor.author Martín, Miguel Ángel spa
dc.contributor.author Lucía Mulas, Alejandro spa
dc.contributor.author Gómez-Foix, Anna M. spa
dc.contributor.author Martí, Ramón spa
dc.contributor.author Andreu, Antoni L. spa
dc.date.accessioned 2013-11-27T17:26:39Z
dc.date.available 2013-11-27T17:26:39Z
dc.date.issued 2010 spa
dc.identifier.citation Nogales-Gadea, G., Mormeneo, E., García-Consuegra, I., Rubio, J. C., Orozco, A., Arenas, J., ..., & Andreu, A. L. (2010). Expression of glycogen phosphorylase isoforms in cultured muscle from patients with McArdle's disease carrying the p.R771PfsX33 PYGM mutation. PloS One, 5(10), e13164. spa
dc.identifier.issn 19326203 spa
dc.identifier.uri http://hdl.handle.net/11268/924
dc.description.abstract Mutations in the PYGM gene encoding skeletal muscle glycogen phosphorylase (GP) cause a metabolic disorder known as McArdle's disease. Previous studies in muscle biopsies and cultured muscle cells from McArdle patients have shown that PYGM mutations abolish GP activity in skeletal muscle, but that the enzyme activity reappears when muscle cells are in culture. The identification of the GP isoenzyme that accounts for this activity remains controversial. In this study we present two related patients harbouring a novel PYGM mutation, p.R771PfsX33. In the patients' skeletal muscle biopsies, PYGM mRNA levels were ∼60% lower than those observed in two matched healthy controls; biochemical analysis of a patient muscle biopsy resulted in undetectable GP protein and GP activity. A strong reduction of the PYGM mRNA was observed in cultured muscle cells from patients and controls, as compared to the levels observed in muscle tissue. In cultured cells, PYGM mRNA levels were negligible regardless of the differentiation stage. After a 12 day period of differentiation similar expression of the brain and liver isoforms were observed at the mRNA level in cells from patients and controls. Total GP activity (measured with AMP) was not different either; however, the active GP activity and immunoreactive GP protein levels were lower in patients' cell cultures. GP immunoreactivity was mainly due to brain and liver GP but muscle GP seemed to be responsible for the differences. These results indicate that in both patients' and controls' cell cultures, unlike in skeletal muscle tissue, most of the protein and GP activities result from the expression of brain GP and liver GP genes, although there is still some activity resulting from the expression of the muscle GP gene. More research is necessary to clarify the differential mechanisms of metabolic adaptations that McArdle cultures undergo in vitro. spa
dc.language.iso eng spa
dc.title Expression of glycogen phosphorylase isoforms in cultured muscle from patients with McArdle's disease carrying the p.R771PfsX33 PYGM mutation spa
dc.type article spa
dc.description.impact 4.411 JCR (2010) Q1, 12/86 Biology spa
dc.identifier.doi 10.1371/journal.pone.0013164 spa
dc.rights.accessRights openAccess en
dc.subject.unesco Genética humana spa
dc.description.filiation UEM spa
dc.peerreviewed Si spa


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