During oxidative stress, the abundant unsaturated fatty acid linoleic acid undergoes lipid peroxidation to produce α,β-
unsaturated epoxy-
keto-
octadecenoic acids (EKODEs). Nonenzymatic autooxidation of linoleic acid generates six major EKODE isomers, which differ from one another in the positioning and the orientation of the epoxy group relative to the keto moiety.
trans-
EKODE-
(E)-
Ib is a biologically active peroxidation product of linoleic acid that is characterized, structurally, by having a
trans carbon-
carbon double bond between the 9-
keto and 12,13-
epoxy groups. It activates an antioxidant response element (ARE) in neuronal cells and induces the expression of ARE-
regulated cytoprotective genes like NQO1.
1 This EKODE also stimulates the synthesis of aldosterone and corticosterone in adrenal cells when supplied at 1-
5 μM.
2,3 This effect appears to be mediated by a rise in intracellular calcium.
4
1. Wang, R., Kern, J.T., Goodfriend, T.L., et al. Activation of the antioxidant response element by specific oxidized metabolites of linoleic acid Prostaglandins Leukot. Essent. Fatty Acids 81(1),53-59(2009).
2. Goodfriend, T.L., Ball, D.L., Raff, H., et al. Oxidized products of linoleic acid stimulate adrenal steroidogenesis Endocr. Res. 28(4),325-330(2002).
3. Goodfriend, T.L., Ball, D.L., Egan, B.M., et al. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion Hypertension 43[part 2],358-363(2004).
4. Payet, M.D., Goodfriend, T.L., Bilodeau, L., et al. An oxidized metabolite of linoleic acid increases intracellular calcium in rat adrenal glomerulosa cells Am. J. Physiol. Endocrinol. Metab. 291,E1160-E1167(2006).
