abstract
Atmospheric particulate matter (PM) with diameters below 10 mu m (PM10) may enter the lungs through inhalation and are linked to various negative health consequences. Emergent evidence emphasizes the significance of cell metabolism as a sensitive target of PM exposure. However, the current understanding of the relationship between PM composition, conventional toxicity measures, and the rewiring of intracellular metabolic processes remains limited. In this work, PM10 sampled at a residential area (urban background, UB) and a traffic-impacted location (roadside, RS) of a Portuguese city was comprehensively characterized in terms of polycyclic aromatic hydrocarbons and plasticizers. Epithelial lung cells (A549) were then exposed for 72 h to PM10 organic extracts and different biological outcomes were assessed. UB and RS PM10 extracts dose-dependently decreased cell viability, induced reactive oxygen species (ROS), decreased mitochondrial membrane potential, caused cell cycle arrest at the G0/G1 phase, and modulated the intracellular metabolic profile. Interestingly, the RS sample, richer in particularly toxic PAHs and plasticizers, had a greater metabolic impact than the UB extract. Changes comprised significant increases in glutathione, reflecting activation of antioxidant defences to counterbalance ROS production, together with increases in lactate, NAD(+), and ATP, which suggest stimulation of glycolytic energy production, possibly to compensate for reduced mitochondrial activity. Furthermore, a number of other metabolic variations hinted at changes in membrane turnover and TCA cycle dynamics, which represent novel clues on potential PM10 biological effects.
keywords
POLYCYCLIC AROMATIC-HYDROCARBONS; OXIDATIVE DNA-DAMAGE; TOXICITY; PM2.5; NANOPARTICLES; FINE; GLUTATHIONE; ACTIVATION; GENERATION; COMPONENTS
subject category
Biochemistry & Molecular Biology; Chemistry
authors
Silva, TD; Alves, C; Oliveira, H; Duarte, IF
our authors
Helena Oliveira
Post-Doc Fellowship
Iola Melissa Fernandes Duarte
Principal Researcher
Tatiana Silva
PhD StudentProjects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
acknowledgements
This work was developed in the scope of the project CICECO-Aveiro Institute of Materials(UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020), financed by national funds throughthe FCT/MEC (PIDDAC), and CESAM (UIDP/50017/2020, UIDB/50017/2020, LA/P/0094/2020),financed by national funds. The NMR spectrometer is part of the National NMR Network (PTNMR),partially supported by Infrastructure Project N degrees 022161 (co-financed by FEDER through COMPETE2020, POCI, and PORL and FCT through PIDDAC).