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Protective action of n-3 fatty acids on benzo[a]pyrene-induced apoptosis through the plasma membrane remodeling-dependent NHE1 pathway

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Béatrice Dendelé, Xavier Tekpli, Kévin Hardonnière, Jørn A Holme, Laure Debure, Daniel Catheline, Volker M Arlt, Eszter Nagy, David H Phillips, Steinar Ovrebø, Steen Mollerup, Mallory Poët, Martine Chevanne, Vincent Rioux, Marie-Thérèse Dimanche-Boitrel, Odile Sergent, Dominique Lagadic-Gossmann

Original languageEnglish
Article numberN/A
Pages (from-to)41-51
Number of pages11
JournalChemico-Biological Interactions
Volume207
Issue numberN/A
DOIs
Publication statusPublished - 25 Jan 2014

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Abstract

Plasma membrane is an early target of polycyclic aromatic hydrocarbons (PAH). We previously showed that the PAH prototype, benzo[a]pyrene (B[a]P), triggers apoptosis via DNA damage-induced p53 activation (genotoxic pathway) and via remodeling of the membrane cholesterol-rich microdomains called lipid rafts, leading to changes in pH homeostasis (non-genotoxic pathway). As omega-3 (n-3) fatty acids can affect membrane composition and function or hamper in vivo PAH genotoxicity, we hypothesized that addition of physiologically relevant levels of polyunsaturated n-3 fatty acids (PUFAs) might interfere with B[a]P-induced toxicity. The effects of two major PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were tested on B[a]P cytotoxicity in the liver epithelial cell line F258. Both PUFAs reduced B[a]P-induced apoptosis. Surprisingly, pre-treatment with DHA increased the formation of reactive B[a]P metabolites, resulting in higher levels of B[a]P-DNA adducts. EPA had no apparent effect on B[a]P metabolism or related DNA damage. EPA and DHA prevented B[a]P-induced apoptotic alkalinization by affecting Na(+)/H(+) exchanger 1 activity. Thus, the inhibitory effects of omega-3 fatty acids on B[a]P-induced apoptosis involve a non-genotoxic pathway associated with plasma membrane remodeling. Our results suggest that dietary omega-3 fatty acids may have marked effects on the biological consequences of PAH exposure.

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