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Time-Point Dependent Activation of Autophagy and the UPS in SOD1G93A Mice Skeletal Muscle.

Oliván S, Calvo AC, Gasco S, Muñoz MJ, Zaragoza P, Osta R - PLoS ONE (2015)

Bottom Line: In particular, the two main intracellular degradation mechanisms, autophagy and the ubiquitin-proteasome degradative system (UPS) have been poorly studied in this tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Genética y Bioquímica (LAGENBIO), Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Immunofluorescence of Beclin1 and LC3 staining.Beclin1 (A) and LC3 (B) staining was performed in skeletal muscle tissue from wild type (WT) and SOD1G93A mice. DAPI staining was also performed (blue). A merged image of the double staining is presented. A representative image presents of 3 independent animals for genotype and disease stages. Scale bars: 100 μm.
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pone.0134830.g003: Immunofluorescence of Beclin1 and LC3 staining.Beclin1 (A) and LC3 (B) staining was performed in skeletal muscle tissue from wild type (WT) and SOD1G93A mice. DAPI staining was also performed (blue). A merged image of the double staining is presented. A representative image presents of 3 independent animals for genotype and disease stages. Scale bars: 100 μm.

Mentions: Moreover, we also characterized the expression partner of Beclin1 and LC3 in the skeletal muscle tissue using immunofluorescence staining. The expression of both proteins was consistent with the pattern described above (Fig 3).


Time-Point Dependent Activation of Autophagy and the UPS in SOD1G93A Mice Skeletal Muscle.

Oliván S, Calvo AC, Gasco S, Muñoz MJ, Zaragoza P, Osta R - PLoS ONE (2015)

Immunofluorescence of Beclin1 and LC3 staining.Beclin1 (A) and LC3 (B) staining was performed in skeletal muscle tissue from wild type (WT) and SOD1G93A mice. DAPI staining was also performed (blue). A merged image of the double staining is presented. A representative image presents of 3 independent animals for genotype and disease stages. Scale bars: 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526523&req=5

pone.0134830.g003: Immunofluorescence of Beclin1 and LC3 staining.Beclin1 (A) and LC3 (B) staining was performed in skeletal muscle tissue from wild type (WT) and SOD1G93A mice. DAPI staining was also performed (blue). A merged image of the double staining is presented. A representative image presents of 3 independent animals for genotype and disease stages. Scale bars: 100 μm.
Mentions: Moreover, we also characterized the expression partner of Beclin1 and LC3 in the skeletal muscle tissue using immunofluorescence staining. The expression of both proteins was consistent with the pattern described above (Fig 3).

Bottom Line: In particular, the two main intracellular degradation mechanisms, autophagy and the ubiquitin-proteasome degradative system (UPS) have been poorly studied in this tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Genética y Bioquímica (LAGENBIO), Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus