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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- 作者：B茅atrice Dendel茅 ; Xavier Tekpli ; K茅vin Hardonni猫re ; J酶rn A. Holme ; Laure Debure ; Daniel Catheline ; Volker M. Arlt ; Eszter Nagy ; David H. Phillips ; Steinar 脴vreb酶 ; Steen Mollerup ; Mallory Po毛t ; Martine Chevanne ; Vincent Rioux ; Marie-Th茅r猫se Dimanche-Boitrel ; Odile Sergent ; Dominique Lagadic-Gossmann
- 关键词：B[a]P ; benzo[a]pyrene ; P450 ; cytochrome P450 ; DHA ; docosahexaenoic acid ; DPA ; docosapentaenoic acid ; EPA ; eicosapentaenoic acid ; ER ; endoplasmic reticulum ; HPLC ; high-performance liquid chromatography ; MUFA ; monounsaturated fatty acid ; PUFA ; polyunsaturated fatty acid ; PAH ; polycylic aromatic hydrocarbon ; SFA ; saturated fatty acid
- 刊名：Chemico-Biological Interactions
- 出版年：25 January, 2014
- 年：2014
- 卷：207
- 期：Complete
- 页码：41-51
- 全文大小：1946 K
文摘
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.