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

Abstract

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.

• Authors: Shiori Ando, Miruto Tanaka, Naoki Chinen, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara
• Journal: In vivo (Athens, Greece) (In Vivo) 2020 Nov-Dec Vol. 34 Issue 6 Pg. 3247-3254 ISSN: 1791-7549 [Electronic] Greece
• PMID: 33144430 (Publication Type: Journal Article)
• Copyright: Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Smn1 protein, mouse
• Survival of Motor Neuron 1 Protein
• Proto-Oncogene Proteins c-akt
• Caspase 3

Topics

• Animals
• Caspase 3 (genetics)
• Cell Differentiation
• Disease Models, Animal
• Mice
• Muscle Fibers, Skeletal
• Muscle, Skeletal
• Proto-Oncogene Proteins c-akt (genetics)
• Survival of Motor Neuron 1 Protein (physiology)