TY - JOUR 
A1 - Luna, Noemí de
AU - Brull, Astrid
AU - Guiu, J. M.
AU - Lucía Mulas, Alejandro
AU - Martín, Miguel Ángel
AU - Arenas, Joaquín
AU - Martí, Ramón
AU - Andreu, Antoni L.
AU - Pinós, Tomás
T1 - Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro
Y1 - 2015
SN - 17548403

UR - http://hdl.handle.net/11268/4004
AB - McArdle disease, also termed ‘glycogen storage disease type V’, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM). It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL) and brain (GP-BB) isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA), a histone deacetylase inhibitor.
KW - Glycogen phosphorylase
KW - Glycogenolysis
KW - McArdle disease
KW - Myotubes
KW - Enfermedades - McArdle
KW - Ejercicio físico
KW - Genética
KW - Ciencia
KW - Salud
LA - eng
ER -