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GSI Treatment Preserves Protein Synthesis in C2C12 Myotubes

Authors :
Charlotte McMullen
Joseph S. Marino
Joshua R. Huot
Brian Thompson
Susan T Arthur
Source :
Cells, Volume 10, Issue 7, Cells, Vol 10, Iss 1786, p 1786 (2021)
Publication Year :
2021

Abstract

It has been demonstrated that inhibiting Notch signaling through γ-secretase inhibitor (GSI) treatment increases myogenesis, AKT/mTOR signaling, and muscle protein synthesis (MPS) in C2C12 myotubes. The purpose of this study was to determine if GSI-mediated effects on myogenesis and MPS are dependent on AKT/mTOR signaling. C2C12 cells were assessed for indices of myotube formation, anabolic signaling, and MPS following GSI treatment in combination with rapamycin and API-1, inhibitors of mTOR and AKT, respectively. GSI treatment increased several indices of myotube fusion and MPS in C2C12 myotubes. GSI-mediated effects on myotube formation and fusion were completely negated by treatment with rapamycin and API-1. Meanwhile, GSI treatment was able to rescue MPS in C2C12 myotubes exposed to rapamycin or rapamycin combined with API-1. Examination of protein expression revealed that GSI treatment was able to rescue pGSK3β Ser9 despite AKT inhibition by API-1. These findings demonstrate that GSI treatment is able to rescue MPS independent of AKT/mTOR signaling, possibly via GSK3β modulation.

Details

ISSN :
20734409
Volume :
10
Issue :
7
Database :
OpenAIRE
Journal :
Cells
Accession number :
edsair.doi.dedup.....50556451faedcf0bee7e824f8de1c6ee