HDGF Protects Retinal Pigment Epithelium from Glyoxal-Induced Ferroptosis via SIRT1/PGC-1α/Nrf2 Pathway.

ABSTRACT: Age-related macular degeneration (AMD) is driven in part by the accumulation of reactive metabolites like glyoxal (GO), which induces retinal pigment epithelium (RPE) degeneration. Here, we demonstrate that GO triggers ferroptosis in human ARPE-19 cells, as characterized by iron-dependent lipid peroxidation, glutathione depletion, and reactive oxygen species (ROS) accumulation. This ferroptotic cell death is coupled with profound mitochondrial dysfunction, featuring network fragmentation and the downregulation of the key regulators MFN2, PGC-1α, and SIRT1. We identify hepatoma-derived growth factor (HDGF) as a potent protector against GO-induced damage. HDGF operates through a dual mechanism: it activates the p38 MAPK/AKT and SIRT1/PGC-1α axes to restore mitochondrial biogenesis and homeos

SUBMITTER: Lin HD 

PROVIDER: S-EPMC12729632 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature