Biphasic stress response in the soleus during reloading after hind limb unloading

Area of Science:

• Exercise physiology
• Muscle biology
• Spaceflight biology

Background:

• Spaceflight and extreme disuse cause rapid skeletal muscle atrophy.
• This atrophy is linked to increased inflammatory signals and impaired stress response proteins like heat shock proteins (HSP) and insulin-like growth factor 1 (IGF-1).
• Muscle mass recovery is delayed upon reloading after unloading, with persistent issues in HSP70 and IGF-1 levels.

Purpose of the Study:

• To investigate the distinct early and late signaling phases during skeletal muscle reloading after unloading.
• To determine if pro-inflammatory signaling and stress response alterations characterize these reloading phases.

Main Methods:

• Adult Sprague-Dawley rats underwent 28 days of hind limb unloading (HU).
• Groups included controls, HU, HU with early reloading (HU-R7), and HU with late reloading (HU-R28).
• Key molecular markers of inflammation, oxidative stress, and stress response proteins were analyzed.

Main Results:

• Hind limb unloading caused significant soleus muscle mass reduction, which persisted after early reloading.
• Nuclear factor κB activation and oxidative stress remained high during reloading.
• Early reloading showed recovery in phosphorylated HSP25 and Akt, but HSP70, heat shock factor 1, and IGF-1 remained depressed. Late reloading saw recovery of these factors.

Conclusions:

• Skeletal muscle reloading exhibits a biphasic response.
• The early phase is characterized by elevated pro-inflammatory signaling (NF-κB, 3-nitrotyrosine) and specific stress protein phosphorylation.
• The late phase is associated with the recovery of muscle mass and key stress response proteins (HSP70, IGF-1).