Time-point dependent activation of autophagy and the UPS in SOD1G93A mice skeletal muscle

Oliván, S. (Universidad de Zaragoza) ; Calvo, A.C. (Universidad de Zaragoza) ; Gasco, S. ; Muñoz, M.J. (Universidad de Zaragoza) ; Zaragoza, P. (Universidad de Zaragoza) ; Osta, R. (Universidad de Zaragoza)
Time-point dependent activation of autophagy and the UPS in SOD1G93A mice skeletal muscle
Resumen: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by a selective loss of motor neurons together with a progressive muscle weakness. Albeit the pathophysiological mechanisms of the disease remain unknown, growing evidence suggests that skeletal muscle can be a target of ALS toxicity. In particular, the two main intracellular degradation mechanisms, autophagy and the ubiquitin-proteasome degradative system (UPS) have been poorly studied in this tissue. In this study we investigated the activation of autophagy and the UPS as well as apoptosis in the skeletal muscle from SOD1G93A mice along disease progression. Our results showed a significant upregulation of proteasome activity at early symptomatic stage, while the autophagy activation was found at presymptomatic and terminal stages. The mRNA upregulated levels of LC3, p62, Beclin1, Atg5 and E2f1 were only observed at symptomatic and terminal stages, which reinforced the time-point activation of autophagy. Furthermore, no apoptosis activation was observed along disease progression. The combined data provided clear evidence for the first time that there is a time-point dependent activation of autophagy and UPS in the skeletal muscle from SOD1G93A mice.
Idioma: Inglés
DOI: 10.1371/journal.pone.0134830
Año: 2015
Publicado en: PloS one 10, 8 (2015), 0134830 [15 p.]
ISSN: 1932-6203

Factor impacto JCR: 3.057 (2015)
Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 11 / 62 = 0.177 (2015) - Q1 - T1
Factor impacto SCIMAGO: 1.427 - Agricultural and Biological Sciences (miscellaneous) (Q1) - Medicine (miscellaneous) (Q1) - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/FIS/PI14-00947
Tipo y forma: Article (Published version)
Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Farmacología (Dpto. Farmacología y Fisiolog.)

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