Perfluorooctane sulfonate mediates GSH degradation leading to oral keratinocytes ferroptosis and mucositis through activation of the ER stress-ATF4-CHAC1 axis DOI Creative Commons
Ningning Yang, Kun Jia, Kazuoki Dai

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 292, P. 117964 - 117964

Published: March 1, 2025

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that induces inflammatory response and oxidative stress in oral mucosa. Ferroptosis, form of cell death characterized by iron-dependent lipid peroxidation (the degradation lipids), was believed to play crucial role pathogenesis mucositis; however, the involvement PFOS-induced ferroptosis remained unclear. Our findings demonstrated PFOS inhibited proliferation induced pro-apoptotic effects cells, with most pronounced observed human keratinocytes (HOK). significantly increased reactive oxygen species (ROS) peroxidation, depleted glutathione (GSH) HOK cells. Notably, decreased peroxidase 4 (GPX4) expression elevated Fe2 + levels, suggesting potential induction ferroptosis. Ferroptosis inhibitors mitigated GSH depletion, subsequently enhancing viability. Mechanistically, endoplasmic reticulum (ER) contributed nuclear translocation (from cytoplasm into nucleus) activating transcription factor (ATF4) up-regulated its downstream target gene Chac1. Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) catalyzed conversion cysteinylglycine 5-oxoproline, resulting depletion-a critical Knocking down CHAC1 attenuated Tauroursodeoxycholic acid (TUDCA), classical ER inhibitor, mucositis inhibiting ATF4/CHAC1 pathway activation. These elucidated toxicological mechanisms proposed therapeutic strategies counteract exposure mucositis.

Language: Английский

Perfluorooctane sulfonate induced ferritinophagy via detyrosinated alpha tubulin-TRIM21-HERC2-regulated NCOA4 degradation in hepatocytes DOI

Ruzhen Feng,

Lingli Hu,

Wei Yang

et al.

Environmental Pollution, Journal Year: 2025, Volume and Issue: unknown, P. 126101 - 126101

Published: March 1, 2025

Language: Английский

Citations

0
Perfluorooctane sulfonate mediates GSH degradation leading to oral keratinocytes ferroptosis and mucositis through activation of the ER stress-ATF4-CHAC1 axis DOI Creative Commons
Ningning Yang, Kun Jia, Kazuoki Dai

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 292, P. 117964 - 117964

Published: March 1, 2025

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that induces inflammatory response and oxidative stress in oral mucosa. Ferroptosis, form of cell death characterized by iron-dependent lipid peroxidation (the degradation lipids), was believed to play crucial role pathogenesis mucositis; however, the involvement PFOS-induced ferroptosis remained unclear. Our findings demonstrated PFOS inhibited proliferation induced pro-apoptotic effects cells, with most pronounced observed human keratinocytes (HOK). significantly increased reactive oxygen species (ROS) peroxidation, depleted glutathione (GSH) HOK cells. Notably, decreased peroxidase 4 (GPX4) expression elevated Fe2 + levels, suggesting potential induction ferroptosis. Ferroptosis inhibitors mitigated GSH depletion, subsequently enhancing viability. Mechanistically, endoplasmic reticulum (ER) contributed nuclear translocation (from cytoplasm into nucleus) activating transcription factor (ATF4) up-regulated its downstream target gene Chac1. Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) catalyzed conversion cysteinylglycine 5-oxoproline, resulting depletion-a critical Knocking down CHAC1 attenuated Tauroursodeoxycholic acid (TUDCA), classical ER inhibitor, mucositis inhibiting ATF4/CHAC1 pathway activation. These elucidated toxicological mechanisms proposed therapeutic strategies counteract exposure mucositis.

Language: Английский

Citations

0