1. Air pollution-derived PM 2.5 impairs mitochondrial function in healthy and chronic obstructive pulmonary diseased human bronchial epithelial cells.
- Author
-
Leclercq B, Kluza J, Antherieu S, Sotty J, Alleman LY, Perdrix E, Loyens A, Coddeville P, Lo Guidice JM, Marchetti P, and Garçon G
- Subjects
- Air Pollutants toxicity, Air Pollution analysis, Air Pollution statistics & numerical data, Bronchi cytology, Epithelial Cells drug effects, Humans, Hypersensitivity, Lung drug effects, Mitochondria metabolism, NF-E2-Related Factor 2, Particulate Matter metabolism, Pulmonary Disease, Chronic Obstructive metabolism, Air Pollutants analysis, Mitochondria drug effects, Particulate Matter analysis, Particulate Matter toxicity
- Abstract
In order to clarify whether the mitochondrial dysfunction is closely related to the cell homeostasis maintenance after particulate matter (PM
2.5 ) exposure, oxidative, inflammatory, apoptotic and mitochondrial endpoints were carefully studied in human bronchial epithelial BEAS-2B, normal human bronchial epithelial (NHBE) and chronic obstructive pulmonary disease (COPD)-diseased human bronchial epithelial (DHBE) cells acutely or repeatedly exposed to air pollution-derived PM2.5 . Some modifications of the mitochondrial morphology were observed within all these cell models repeatedly exposed to the highest dose of PM2.5 . Dose- and exposure-dependent oxidative damages were reported in BEAS-2B, NHBE and particularly COPD-DHBE cells acutely or repeatedly exposed to PM2.5 . Nuclear factor erythroid 2-p45 related factor 2 (NRF2) gene expression and binding activity, together with the mRNA levels of some NRF2 target genes, were directly related to the number of exposures for the lowest PM2.5 dose (i.e., 2 μg/cm2 ), but, surprisingly, inversely related to the number of exposures for the highest dose (i.e., 10 μg/cm2 ). There were dose- and exposure-dependent increases of both nuclear factor kappa-B (NF-κB) binding activity and NF-κB target cytokine secretion in BEAS-2B, NHBE and particularly COPD-DHBE cells exposed to PM2.5 . Mitochondrial ROS production, membrane potential depolarization, oxidative phosphorylation, and ATP production were significantly altered in all the cell models repeatedly exposed to the highest dose of PM2.5 . Collectively, our results indicate a cytosolic ROS overproduction, inducing oxidative damage and activating oxygen sensitive NRF2 and NF-k B signaling pathways for all the cell models acutely or repeatedly exposed to PM2.5 . However, one of the important highlight of our findings is that the prolonged and repeated exposure in BEAS-2B, NHBE and in particular sensible COPD-DHBE cells further caused an oxidative boost able to partially inactivate the NRF2 signaling pathway and to critically impair mitochondrial redox homeostasis, thereby producing a persistent mitochondrial dysfunction and a lowering cell energy supply., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF