title: 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.
authors: SeRAIC, IRSET, Université de Rennes, France.
authors: Abdullah
authors: A
authors: Mayati
authors: Eric
authors: E
authors: Le Ferrec
authors: Dominique
authors: D
authors: Lagadic-Gossmann
authors: Olivier
authors: O
authors: Fardel
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D001571:Benzoflavones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004787:Environmental Pollution; D055785:Gene Knockdown Techniques; D006801:Humans; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D001571:Benzoflavones; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D002118:Calcium