Exposure to diesel exhaust particles accelerated neuronal cell death in xenoferroptosis-susceptible cells
Yan, Hong Zhang, Leshan Bergsma, Daan P Gadjdjoe, Phoeja S Tosato, Alessandra Rahman, Mohammad S Mulder, Kristel van Trigt, Joelle Rafie, Karim Mol-van der Veen, Christina HTJ
Yan, Hong
Zhang, Leshan
Bergsma, Daan P
Gadjdjoe, Phoeja S
Tosato, Alessandra
Rahman, Mohammad S
Mulder, Kristel
van Trigt, Joelle
Rafie, Karim
Mol-van der Veen, Christina HTJ
Series / Report no.
Open Access
Type
Article
Language
en
Date of publication
2025-08-22
Year of publication
Research Projects
Organizational Units
Journal Issue
Title
Exposure to diesel exhaust particles accelerated neuronal cell death in xenoferroptosis-susceptible cells
Translated Title
Published in
J Environ Sci-China 2026; 163:22–36
Abstract
Air pollution is a public health concern and has amongst others been associated with the development or aggravation of neurodegenerative diseases. However, the underlying biological pathways remain poorly defined. Ferroptosis, a cell death dependent on lipid peroxidation, is associated with aging and the pathology of neurodegenerative diseases. In this study, we investigated whether exposure to particulate matter (PM)-diesel exhaust particles (DEP), biodiesel exhaust particles (BioDEP), and black carbon (BC)-could affect neuronal survival in conditions of increased vulnerability to ferroptotic cell death. Applying low PM concentrations up to 100 μg/mL to mouse hippocampal (HT22) neuronal cells did not induce substantial cell death. However, a combined exposure (or stimulation) of ferroptotic pathway inducers (glutamate, erastin, and RAS-selective lethal small molecule 3 (RSL3)) decreased neuronal cell survival with PM. As studied in detail for DEP, the combined challenge led to impaired cell metabolism, increased lipid peroxidation, calcium deregulation, mitochondrial reactive oxygen species (ROS) production and fragmentation, and led to xenoferroptotic cell death. Our findings suggest that PM in combination with a ferroptotic pathway inducer can accelerate neuronal cell death, increasing the pathology of neurodegenerative diseases in ferroptosis-susceptible cells.