Pb induces ferroptosis in choroid plexus epithelial cells via Fe metabolism.

Pb can enhance blood-cerebrospinal fluid barrier (BCSFB) permeability and accumulate in brain tissue, leading to central nervous system (CNS) dysfunction. Choroid plexus (CP) epithelial cells are the main components of the BCSFB with crucial functions in BCSFB maintenance. However, the mechanism by which Pb exposure affects CP epithelial cells remains unclear. Here, ferroptosis was identified as the major programmed cell death modality by sophisticated high-throughput sequencing and biochemical investigations in primary cultured CP epithelial cells following Pb exposure. Bioinformatics analysis using the ferroptosis database revealed that 16 ferroptosis-related genes were differentially expressed in primary cultured CP epithelial cells following Pb exposure. Among them, Gpx4, Slc7a11, Tfrc, and Slc40a1 were hub ferroptosis-related genes. In addition, CP epithelial cells can be impaired when the concentration of the Pb2+ reached 2050 μg/L (10 μM PbAc), which included the decrease of cell viability, Gpx4 and Slc7a11 proteins expression, etc. Moreover, inhibition of ferroptosis enhanced CP epithelial cell viability and reduced BCSFB permeability in vitro following Pb exposure. In summary, ferroptosis of CP epithelial cells is involved in BCSFB dysfunction following Pb exposure. Gpx4, Slc7a11, Tfrc, and Slc40a1 are hub ferroptosis-related genes in CP epithelial cells.