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

作者：Mayati Abdullah; Le Ferrec Eric^*; Lagadic Gossmann Dominique; Fardel Olivier

来源：Environmental Toxicology, 2012, 27(9): 556-562.

DOI：10.1002/tox.20675

• calcium
• polycyclic aromatic hydrocarbon
• Aryl hydrocarbon receptor
• endothelial cell
• benzo(a)pyrene

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, a-naphthoflavone, a flavonoid 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.

• 出版日期2012-9