The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

Anna Wójtowicz , Agnieszka Sitarz , Małgorzata Szczęsna , Konrad A. Szychowski

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in various plastic compounds, such as polyvinyl chloride (PVC), and products including baby toys, packaging films and sheets, medical tubing, and blood storage bags. Epidemiological data suggest that phthalates increase the risk of the nervous system disorders; however, the impact of DEHP on the brain cells and the mechanisms of its action have not been clarified. The aim of the present study was to investigate the effects of DEHP on production of reactive oxygen species (ROS) and aryl hydrocarbon receptor (AhR), as well as Cyp1a1 and Cyp1b1 mRNA and protein expression in primary mouse cortical neurons and glial cells in the in vitro mono-cultures. Our experiments showed that DEHP stimulated ROS production in both types of mouse neocortical cells. Moreover, the results strongly support involvement of the AhR/Cyp1A1 signaling pathway in the action of DEHP in neurons and glial cells. However, the effects of DEHP acting on the AhR signaling pathways in these two types of neocortical cells were different. In neurons, AhR mRNA expression did not change, but AhR protein expression decreased in response to DEHP. A similar trend was observed for Cyp1a1 and Cyp1b1 mRNA and protein expression. Failure to induce Cyp1a1 in neurons was confirmed by EROD assay. In primary glial cells, a decrease in AhR protein level was accompanied by a decrease in AhR mRNA expression. In glial cells, mRNA and protein expression of Cyp1a1 as well as Cyp1a1-related EROD activity were significantly increased. As for Cyp1b1, both in neurons and glial cells Cyp1b1 mRNA expression did not significantly change, whereas Cyp1b1 protein level were decreased. We postulate that developmental exposure to DEHP which dysregulates AhR/Cyp1a1 may disrupt defense processes in brain neocortical cells that could increase their susceptibility to environmental toxins.
Author Anna Wójtowicz (FoAS / DoAB)
Anna Wójtowicz,,
- Department of Animal Biotechnology
, Agnieszka Sitarz (DoAS / DoAB)
Agnieszka Sitarz,,
- Department of Animal Biotechnology
, Małgorzata Szczęsna (FoAS / DoAB)
Małgorzata Szczęsna,,
- Department of Animal Biotechnology
, Konrad A. Szychowski
Konrad A. Szychowski,,
-
Journal seriesNeurotoxicity Research, ISSN 1029-8428, e-ISSN 1476-3524, (N/A 70 pkt)
Issue year2019
Vol35
No1
Pages183-195
Publication size in sheets0.6
Keywords in EnglishDEHP, AhR, Cyp1a1, Glia, Neurons, ROS
ASJC Classification2800 General Neuroscience; 3005 Toxicology
DOIDOI:10.1007/s12640-018-9946-7
URL https://link.springer.com/content/pdf/10.1007%2Fs12640-018-9946-7.pdf
Internal identifierWHiBZ/2019/7
Languageen angielski
LicenseJournal (articles only); author's original; Uznanie Autorstwa (CC-BY); after publication
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Wójtowicz2019_Article_TheActionOfDi-2-EthylhexylPhth.pdf of 18-02-2020
1,5 MB
Score (nominal)70
Score sourcejournalList
Publication indicators WoS Citations = 1; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.823; WoS Impact Factor: 2018 = 3.311 (2) - 2018=3.245 (5)
Citation count*
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FinansowanieThis work was supported by grant from the Polish National Science Centre 2012/07/B/NZ4/00238.
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