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

Abstract : 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 ([Ca(2+)](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 [Ca(2+)](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 [Ca(2+)](i) in human endothelial HMEC-1 cells. Moreover, α-naphthoflavone, a flavonoïd antagonist of AhR, was also able to induce [Ca(2+)](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 [Ca(2+)](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 [Ca(2+)](i) induction in an AhR-independent manner. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.
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Submitted on : Tuesday, March 20, 2012 - 1:15:18 PM
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Abdullah Mayati, Eric Le Ferrec, Dominique Lagadic-Gossmann, Olivier Fardel. Aryl hydrocarbon receptor-independent up-regulation of intracellular calcium concentration by environmental polycyclic aromatic hydrocarbons in human endothelial HMEC-1 cells.. Environmental Toxicology, Wiley, 2011, 27 (9), pp.556-562. ⟨10.1002/tox.20675⟩. ⟨hal-00680889⟩

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