CSE/H₂S/SESN2 Signalling Mediates the Protective Effect of Exercise Against Immobilization-Induced Muscle Atrophy in...

Area of Science:

• Muscle physiology
• Biochemistry
• Cellular biology

Background:

• Hydrogen sulphide (H2S), a gasotransmitter, possesses antioxidant properties and may replicate exercise-induced muscle protection.
• The precise role of H2S in muscle atrophy and exercise interventions remains incompletely understood.

Purpose of the Study:

• To investigate the protective mechanisms of H2S against disuse-induced muscle atrophy.
• To explore the involvement of the SESN2/Nrf2 signaling pathway in H2S-mediated muscle protection.
• To evaluate H2S as a potential therapeutic mimic of exercise for muscle preservation.

Main Methods:

• Hindlimb immobilization followed by exercise or pharmacological treatment with an H2S donor (NaHS) or CSE inhibitor (PAG) in mice.
• In vitro studies using C2C12 myotubes exposed to oxidative stress and treated with NaHS.
• Assessment of muscle mass, fiber cross-sectional area (CSA), collagen deposition, and oxidative stress markers using histology and Western blot.

Main Results:

• Exercise intervention and NaHS administration significantly increased muscle mass, CSA, and reduced collagen deposition compared to immobilization.
• Pharmacological inhibition of CSE attenuated exercise-induced benefits, while NaHS mimicked exercise effects.
• NaHS upregulated SESN2, Nrf2, HO-1, and NQO1 expression in vitro and in vivo.
• SESN2 deficiency abolished NaHS-mediated muscle protection, confirming SESN2's crucial role.

Conclusions:

• H2S confers protection against disuse-induced muscle atrophy by enhancing antioxidant defenses via the SESN2/Nrf2 pathway.
• H2S acts as an exercise-mimetic agent, offering a potential therapeutic avenue for preserving muscle mass and function.