FoxO1 overexpression promotes for the early activation of Akt/mTOR signaling in skeletal myotubes

Abstract

The regulation of skeletal muscle is dependent upon the balance between protein synthesis and protein degradation. Previous studies indicate that FoxO1 expression plays an important role in regulating this balance. It has been demonstrated that activation of Akt and its downstream targets such as mTOR and p70s6kare associated with protein synthesis. However, there is little evidence on the role of the Akt/mTOR pathway in association with FoxO1 activity. In order to study the role FoxO1 plays in regulating skeletal muscle atrophy and hypertrophy, a cell culture model was used in which FoxO1 estrogen receptor fusion proteins were transfected into skeletal muscle myoblasts and grown into skeletal muscle myotubes. The myotubes were treated with 4-hydroxytamoxifen (4-OHT) to activate the FoxO1 estrogen receptor fusion proteins or treated with a vehicle control for 24, 48, and 72 hours. The cells were collected and run through western blots using phospho-Akt (ser473), total Akt, phospho-p70s6k and total p70s6k antibodies. Cells expressing FoxO1 activity and treated with 4-OHT had slightly decreased p70s6k activity and had increased Akt activity compared to control cells. These findings provide support that FoxO1 overexpression promotes for elevations in Akt/mTOR signaling. Thus, the overexpression of FoxO1 may allow for suppression or degradation of the Akt/mTOR pathway and this link needs to be further investigated.