Embryogenesis is dependent upon 12-lipoxygenase, 5-lipoxygenase, and α-tocopherol to modulate polyunsaturated fatty acid status and the production of oxidized fatty acids in zebrafish Public Deposited

Embryogenesis is dependent upon 12-lipoxygenase, 5-lipoxygenase, and alpha-tocopherol to modulate polyunsaturated fatty acid status and the production of oxidized fatty acids in zebrafish

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/df65vd07b

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  • Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are polyunsaturated fatty acids required for proper embryonic development, specifically neurodevelopment. However, little is known regarding their conversion to other metabolites during embryogenesis. The oxidation of ARA gives rise to the biologically active eicosanoids and the oxidation of DHA gives rise to the biologically active docosanoids. The oxidation of ARA and DHA occurs through enzymatic processes, via lipoxygenase (LOX), or non-enzymatic processes, via radical-mediated lipid peroxidation. We hypothesize that oxidation of ARA and DHA via LOX is required for proper embryonic development. Additionally, we hypothesize that α-tocopherol, a potent lipid soluble antioxidant, mediates the conversion of ARA and DHA to their respective oxidized metabolites. Using zebrafish as a model of vertebrate embryogenesis, we found that the selective knockdown of either 12-LOX or 5-LOX decreased the production of docosanoids, altered fatty acid homeostasis, and increased the incidence of malformations and mortality in embryos by 24 hours post fertilization. α-Tocopherol deficiency also increased the incidence of malformations and mortality during embryogenesis, and in its absence, increased oxidized metabolites of ARA and DHA and decreased fatty acids concentrations. Therefore, oxidized metabolites of ARA and DHA perform crucial functions during embryonic development, but the production of oxidized fatty acids must be balanced with antioxidant bioavailability for proper embryogenesis.
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