Genotoxicant exposure, activation of the aryl hydrocarbon receptor, and lipid peroxidation in cultured human alveolar type II A549 cells

0532294 - ÚEM 2021 RIV NL eng J - Článek v odborném periodiku
Rössner ml., Pavel - Líbalová, Helena - Vrbová, Kristýna - Červená, Tereza - Rössnerová, Andrea - Elzeinová, Fatima - Milcová, Alena - Nováková, Zuzana - Topinka, Jan
Genotoxicant exposure, activation of the aryl hydrocarbon receptor, and lipid peroxidation in cultured human alveolar type II A549 cells.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis. Roč. 853, SI (2020), č. článku 503173. ISSN 1383-5718. E-ISSN 1879-3592
Grant CEP: GA ČR(CZ) GA16-14631S; GA MŠMT(CZ) LO1508
Institucionální podpora: RVO:68378041
Klíčová slova: aryl hydrocarbon receptor * extractable organic matter * lipid peroxidation
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 2.873, rok: 2020
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/abs/pii/S1383571820300437?via%3Dihub

The aryl hydrocarbon receptor (AhR) transcription factor is activated by polycyclic aromatic hydrocarbons (PAH) and other ligands. Activated AhR binds to dioxin responsive elements (DRE) and initiates transcription of target genes, including the gene encoding prostaglandin endoperoxide synthase 2 (PTGS-2), which is also activated by the transcription factor NF-kappa B. PTGS-2 catalyzes the conversion of arachidonic acid (AA) into prostaglandins, thromboxanes or isoprostanes. 15-F2t-Isoprostane (IsoP), regarded as a universal marker of lipid peroxidation, is also induced by PAH exposure. We investigated the processes associated with lipid peroxidation in human alveolar basal epithelial cells (A549) exposed for 4 h or 24 h to model PAH (benzo[a]pyrene, BaP, 3-nitrobenzanthrone, 3-NBA) and organic extracts from ambient air particulate matter (EOM), collected in two seasons in a polluted locality. Both EOM induced the expression of CYP1A1 and CYP1B1, 24 h treatment significantly reduced PTGS-2 expression. IsoP levels decreased after both exposure periods, while the concentration of AA was not affected. The effects induced by BaP were similar to EOM except for increased IsoP levels after 4 h exposure and elevated AA concentration after 24 h treatment. In contrast, 3-NBA treatment did not induce CYP expression, had a weak effect on PTGS-2 expression, and, similar to BaP, induced IsoP levels after 4 h exposure and AA levels after 24 h treatment. All tested compounds induced the activity of NF-kappa B after the longer exposure period. In summary, our data suggest that EOM, and partly BaP, reduce lipid peroxidation by a mechanism that involves AhR-dependent inhibition of PTGS-2 expression. The effect of 3-NBA on IsoP levels is probably mediated by a different mechanism independent of AhR activation.
Trvalý link: http://hdl.handle.net/11104/0310824