Aryl hydrocarbon receptor-independent up-regulation of intracellular calcium concentration by environmental polycyclic aromatic hydrocarbons in human endothelial HMEC-1 cells

Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (B(a)P) constitute a major family of widely‐distributed environmental toxic contaminants, known as potent ligands of the aryl hydrocarbon receptor (AhR). B(a)P has been recently shown to trigger an early and transient increase of intracellular calcium concentration (Ca²⁺]_i), involved in AhR‐related up‐regulation of target genes by B(a)P. This study was designed to determine whether AhR may play a role in Ca²⁺]_i induction provoked by B(a)P. We demonstrated that, in addition to B(a)P, various PAHs, including pyrene and benzo(e)pyrene, known to not or only very poorly interact with AhR, similarly up‐regulated Ca²⁺]_i in human endothelial HMEC‐1 cells. Moreover, α‐naphthoflavone, a flavonoïd antagonist of AhR, was also able to induce Ca²⁺]_i. Knocking‐down AhR expression in HMEC‐1 cells through transfection of siRNAs, was finally demonstrated to not prevent B(a)P‐mediated induction of Ca²⁺]_i, whereas it efficiently counteracted B(a)P‐mediated induction of the referent AhR target gene cytochrome P‐450 1B1. Taken together, these data demonstrate that environmental PAHs trigger Ca²⁺]_i induction in an AhR‐independent manner. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.