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Nonenzymatic oxygenated metabolite of docosahexaenoic acid, 4( RS )‐4‐F 4t ‐neuroprostane, acts as a bioactive lipid molecule in neuronal cells
Author(s) -
Lee Yiu Yiu,
Galano JeanMarie,
Leung Ho Hang,
Balas Laurence,
Oger Camille,
Durand Thierry,
Lee Jetty ChungYung
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13774
Subject(s) - docosahexaenoic acid , neuroprotection , metabolite , eicosapentaenoic acid , pharmacology , antioxidant , in vivo , biochemistry , chemistry , biology , fatty acid , polyunsaturated fatty acid , microbiology and biotechnology
Docosahexaenoic acid (DHA), an abundant fatty acid in the brain, is susceptible to auto‐oxidation in situ and releases metabolites such as F 4 ‐neuroprostane (4‐F 4t ‐NeuroP). The presence of 4‐F 4t ‐NeuroP in the brain is not well explored. In this study, 4‐F 4t ‐NeuroP was introduced into neuroblastoma cells (SH‐SY5Y) and, by in vivo infusion, into rodents. Targeted lipidomic analysis of liver and brain tissues shows significant elevation of anti‐inflammatory hydroxylated DHA metabolites and an isomer of neuroprotectin D1, suggesting potential beneficial bioactivities of 4‐F 4t ‐NeuroP. Additionally, 4‐F 4t ‐NeuroP treatment in SH‐SY5Y cells and primary neuronal culture consistently upregulates the transcriptional level of the antioxidant enzyme heme oxygenase‐1, but the effect is reduced when 4‐F 4t ‐NeuroP is further oxidized. Our data suggest that 4‐F 4t ‐NeuroP could be neuroprotective in the native state but may have disadvantageous bioactivity when oxidized extensively.