Frontiers in Toxicology · Published 2026-05-10 · DOI 10.3389/ftox.2026.1774625
Introduction Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, but their role in bladder epithelial injury remains unclear.MethodsSV-HUC-1 cells were exposed to PFOA and PFOS. Cell viability, lipid peroxidation, and ROS levels were assessed using CCK-8 assay, flow cytometry, and transmission electron microscopy. Protein expression and ubiquitination were analyzed by Western blotting and molecular docking.ResultsPFOA and PFOS induced ferroptosis in bladder epithelial cells, characterized by increased lipid peroxidation and ROS levels. Mechanistically, PFOA/PFOS inhibited ACSL4 ubiquitination at K593 and K690, leading to its stabilization and promoting ferroptosis. Knockdown of ACSL4 significantly reversed these effects.DiscussionThese findings reveal a novel mechanism by which PFAS induce ferroptosis via regulation of ACSL4 ubiquitination, providing new insights into PFAS-induced bladder toxicity.
Abstract from DOAJ. Public domain (CC0 1.0).
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