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7521345 
Journal Article 
Nrf2 protects against diverse PM2.5 components-induced mitochondrial oxidative damage in lung cells 
Pardo, M; Xu, F; Shemesh, M; Qiu, X; Barak, Y; Zhu, T; Rudich, Y 
2019 
Science of the Total Environment
ISSN: 0048-9697
EISSN: 1879-1026 
669 
303-313 
English 
Nrf2 is an important transcription factor implicated in the oxidative stress response, which has been reported to play an important role in the way by which air pollution particulate matter (PM2.5) induces adverse health effects. This study investigates the mechanism by which Nrf2 exerts its protective effect in PM2.5 induced toxicity in lung cells. Lung cells silenced for Nrf2 (shNrf2) demonstrated diverse susceptibility to various PM extracts; water extracts containing high levels of dissolved metals exhibited higher capacity to generate mitochondrial reactive oxygen species (ROS) and hence increased oxidative stress levels. Organic extracts containing high levels of polycyclic aromatic hydrocarbons (PAHs) increased mortality and reduced ROS production in the silenced cells. shNrf2 cells exhibited a higher basal mitochondrial respiration rate compared to the control cells. Following exposure to water extracts, the mitochondrial respiration increased, which was not observed with the organic extracts. shNrf2 cells exposed to the organic extracts showed lower mitochondrial membrane potential and lower mtDNA copy number. Nrf2 may act as a signaling mediator for the mitochondria function following PM2.5 exposure.