SMN Protein Contributes to Skeletal Muscle Cell Maturation Via Caspase-3 and Akt Activation

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved..

BACKGROUND/AIM: In spinal muscular atrophy (SMA), systemic deficiency of survival motor neurons (SMN) caused by loss or mutation of SMN1 leads to SMA symptoms. SMA was, for a long time, considered as a selective motor-neuron disease. However, accumulated evidence suggests that skeletal muscle cells are affected by low levels of SMN protein. The purpose of this study was to elucidate the function of SMN protein in skeletal cell differentiation and maturation.

MATERIALS AND METHODS: In SMNΔ7 mice, which exhibit a systemic reduction of SMN protein, muscle atrophy was evaluated. To direct the effect of SMN against muscle cells, SMN functions were examined by knockdown of SMN in mouse myoblasts cell line C2C12 using siRNA.

RESULTS: SMNΔ7 mice showed muscle atrophy accompanied by decreased both expression of a myogenesis marker and a proliferating marker. In SMN-knockdown myoblasts, early expression of myosin heavy chain and reduced multinuclear myotube formation were found. Decreased caspase-3 activity and reduced phosphorylation of Akt were observed at an early stage of differentiation in SMN-knockdown myoblasts.

CONCLUSION: A critical role of SMN protein in muscle cell differentiation via caspase-3 and Akt activation was shown.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:34

Enthalten in:

In vivo (Athens, Greece) - 34(2020), 6 vom: 03. Nov., Seite 3247-3254

Sprache:

Englisch

Beteiligte Personen:

Ando, Shiori [VerfasserIn]
Tanaka, Miruto [VerfasserIn]
Chinen, Naoki [VerfasserIn]
Nakamura, Shinsuke [VerfasserIn]
Shimazawa, Masamitsu [VerfasserIn]
Hara, Hideaki [VerfasserIn]

Links:

Volltext

Themen:

Caspase 3
EC 2.7.11.1
EC 3.4.22.-
Journal Article
Myotube formation
Proto-Oncogene Proteins c-akt
Skeletal muscles
Smn1 protein, mouse
Spinal muscular atrophy
Survival motor neurons
Survival of Motor Neuron 1 Protein

Anmerkungen:

Date Completed 18.06.2021

Date Revised 31.05.2022

published: Print

Citation Status MEDLINE

doi:

10.21873/invivo.12161

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317126881