Differential induction of electrophile-responsive element-regulated genes by n-3 and n-6 polyunsaturated fatty acids |
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Authors: | van Beelen Vincent A Aarts Jac M M J G Reus Astrid Mooibroek Hans Sijtsma Lolke Bosch Dirk Rietjens Ivonne M C M Alink Gerrit M |
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Affiliation: | Division of Toxicology, Wageningen University and Research Center, Tuinlaan 5, 6703 HE Wageningen, The Netherlands. Vincent.vanBeelen@wur.nl |
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Abstract: | In this study the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid and docosahexaenoic acid appear to be effective inducers of electrophile-responsive element (EpRE) regulated genes, whereas the n-6 PUFA arachidonic acid is not. These n-3 PUFAs need to be oxidized to induce EpRE-regulated gene expression, as the antioxidant vitamin E can partially inhibit the PUFA induced dose-dependent effect. Results were obtained using a reporter gene assay, real-time RT-PCR and enzyme activity assays. The induction of EpRE-regulated phase II genes by n-3 PUFAs may be a major pathway by which n-3 PUFAs, in contrast to n-6 PUFAs, are chemopreventive and anticarcinogenic. |
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Keywords: | AA, arachidonic acid DHA, docosahexaenoic acid EPA, eicosapentaenoic acid EpRE, electrophile-responsive element GST(P1), glutathione S-transferase (Pi 1) Keap1, Kelch-like ECH-associated protein 1 MT1, metallothionein 1 NQO1, NAD(P)H:quinone oxido-reductase 1 Nrf2, NF-E2-related factor 2 PUFA, polyunsaturated fatty acid |
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