27-Hydroxycholesterol Inhibits Muscle Cell Viability via Mitochondrial Dysfunction: Protective Role of ROS-induced HIF-1α - PubMed
5 hours ago
- #Muscle Atrophy
- #27-Hydroxycholesterol
- #Mitochondrial Dysfunction
- 27-Hydroxycholesterol (27OHC) decreases skeletal muscle viability by activating pro-apoptotic signaling pathways.
- RNA sequencing shows 27OHC treatment upregulates 767 genes (linked to hypoxia-inducible factor 1-alpha response) and downregulates 989 genes (involved in phosphoinositide 3-kinase pathway and muscle differentiation).
- 27OHC induces myoblast cell death via reactive oxygen species (ROS) generation, mitochondrial dysfunction, and disruption of mitochondrial membrane potential.
- 27OHC reduces mitochondrial gene expression via glycogen synthase kinase-3 beta activation, increasing mitochondrial ROS.
- Hypoxia-inducible factor 1-alpha (HIF-1α) induction by 27OHC activates cellular defense mechanisms against oxidative damage.
- 27OHC impairs myotube differentiation and fusion index; HIF-1α knockdown worsens tube formation impairment.
- Mice treated with 27OHC show reduced exercise endurance, decreased muscle cross-sectional area, and impaired muscle recovery after injury.
- Elevated plasma 27OHC levels in elderly suggest pharmacological inhibition could treat age-related muscle atrophy.