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

TitleProtective action of n-3 fatty acids on benzo[a]pyrene-induced apoptosis through the plasma membrane remodeling-dependent NHE1 pathway.
Publication TypeJournal Article
Year of Publication2014
AuthorsDendelé B, Tekpli X, Hardonnière K, Holme JA, Debure L, Catheline D, Arlt VM, Nagy E, Phillips DH, Ovrebø S, Mollerup S, Poët M, Chevanne M, Rioux V, Dimanche-Boitrel M-T, Sergent O, Lagadic-Gossmann D
JournalChem Biol Interact
Volume207
Pagination41-51
Date Published01/2014
ISSN1872-7786
KeywordsAnimals, Apoptosis, Benzo(a)pyrene, Cell Line, Cell Membrane, Cholesterol, Cytochrome P-450 Enzyme System, DNA Damage, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Hydrogen-Ion Concentration, Intracellular Space, Lipids, Membrane Microdomains, Models, Biological, Protective Agents, Protein Transport, Rats, Signal Transduction, Sodium-Hydrogen Antiporter, Tumor Suppressor Protein p53
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.

DOI10.1016/j.cbi.2013.11.002
Alternate JournalChem. Biol. Interact.
PubMed ID24246761