Etudes des mécanismes cellulaires impliqués dans la signalisation calcique lors de l'exposition à des contaminants environnementaux : les hydrocarbures aromatiques polycycliques (HAPs)
Polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (B(a)P), constitute a major family of widely-distributed environmental contaminants known to promote various deleterious effects towards human health, including the development of cancers and cardiovascular pathologies. Most of these effects have been linked to the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor primarily located in the cytosol. In addition, PAHs have been shown to elicit an early and transient increase in intracellular calcium concentration, that is required for up-regulation of AhR-mediated induction of PAHs target genes and PAHs toxicity. However, the origin of PAHs-related calcium signal still yet unknown. Our results show that AhR is not involved in the calcium signal triggered by PAHs in our models. In addition, we demonstrated the prototypical PAH B(a)P can bind to s2ADR and to consequently activate a G protein/AC/cAMP/Epac-1/IP3 pathway, which in turn resulted into [Ca2+]i increase, required for B(a)P-mediated induction of the AhR gene target CYP1B1. Such data are therefore consistent with a previously-unsuspected implication of the s2ADR system in deleterious effects of environmental PAHs.