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SIRT1 Prevents Ferroptosis in Corneal Epithelial Cells by Enhancing HIF1α Protein Stability in Dry Eye Disease - PubMed

4 hours ago
  • #dry eye disease
  • #SIRT1
  • #ferroptosis
  • Hyperosmotic stress from tear film instability worsens oxidative damage in corneal epithelial cells in dry eye disease (DED).
  • Ferroptosis, an iron-dependent cell death mechanism driven by lipid peroxidation, plays a critical role in DED.
  • SIRT1 downregulation under hyperosmotic stress promotes ferroptosis in corneal epithelial cells.
  • SIRT1 positively regulates GPX4, a key mediator of ferroptosis, and its activation (e.g., via SRT1720) reduces oxidative damage and ferroptosis.
  • SIRT1 stabilizes HIF1α by deacetylating it, preventing its degradation via the ubiquitin-proteasome pathway.
  • The SIRT1-HIF1α axis enhances GPX4 levels, inhibiting ferroptosis and suggesting a therapeutic strategy for DED.