Hypoxia-Induced ROS Contribute to Myoblast Pyroptosis during Obstructive Sleep Apnea via the NF-κB/HIF-1α Signaling...

Area of Science:

• Cell Biology
• Pathophysiology
• Molecular Medicine

Background:

• Obstructive sleep apnea (OSA) is linked to tissue hypoxia, oxidative stress, and systemic inflammation.
• Hypoxia-induced reactive oxygen species (ROS) can impair cell survival and cause tissue injury.

Purpose of the Study:

• To investigate if hypoxia-induced ROS activate pyroptosis in myoblasts, a key cell type in skeletal muscle.
• To explore the therapeutic potential of targeting ROS in hypoxia-related muscle damage.

Main Methods:

• Utilized OSA mouse models and in vitro C2C12 myoblast cultures under hypoxic conditions.
• Assessed cell death, pyroptosis markers (caspase-1, GSDMD), ROS levels, and signaling pathways (NF-κB, HIF-1α).
• Administered N-acetylcysteine (NAC), an ROS scavenger, to evaluate its protective effects.

Main Results:

• Hypoxia induced pyroptotic cell death in skeletal muscle of OSA mice and C2C12 myoblasts.
• ROS overproduction was observed in hypoxia-exposed myoblasts, activating caspase-1 and GSDMD.
• NAC treatment mitigated hypoxia-induced cell swelling, inflammation, pyroptosis, and normalized signaling pathways.

Conclusions:

• Hypoxia-induced ROS directly contribute to myoblast pyroptosis, a mechanism implicated in OSA pathophysiology.
• Targeting ROS with antioxidants like NAC shows promise for treating hypoxia-induced cell death and tissue injury.
• Findings highlight ROS as a potential therapeutic target for OSA and other hypoxia-related conditions.