Purinergic Receptor Antagonist A438079 Disrupts Benzo[a]pyrene-Mediated IL-1β, CYP1A and CYP1B Transcript Induction Pathway in Zebrafish: Insights into Possible Mechanisms.
DOI:
https://doi.org/10.5132/eec.2022.02.09Keywords:
A438079, benzo[a]pyrene, CYP1B1, gene transcription, P2X7, zebrafishAbstract
The deleterious effects of benzo[a]pyrene are mainly due its metabolites generated by CYP1 metabolism. P2X7 is an important member of purinergic receptors involved in diverse cell signaling cascades, as the inflammasome pathway. Receptor blocking has beneficial effects in several models of inflammatory and neurological diseases. In our study, we show for the first time that the A438079, a “selective” P2X7 antagonist, promotes a down regulation in IL-1β, CYP1A1 and CYP1B1 gene transcription in Danio rerio gills exposed to benzo[a]pyrene. Our results shows a modulation of IL-1β and CYP1 mRNAs, suggesting a possible novel mechanism involving the P2X7 receptor in benzo[a]pyrene-mediated CYP1 induction. Nevertheless, as A438079 was also proven to block the membrane ATP channel pannexin-1, the effects of this compound on downregulating CYPs transcription would be also due to a disruption on Ca2+ influx necessary to activate CYPs transcription by the AhR-Arnt pathway.
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