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Elovanoids are nove...
Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-07-13
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Springer Science and Business Media LLC,2017
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:136238375
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http://kipublications.ki.se/Default.aspx?queryparsed=id:136238375URI
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https://doi.org/10.1038/s41598-017-05433-7DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Docosahexaenoic acid (DHA, 22:6 n-3) is abundant in the retina and is enzymatically converted into pro-homeostatic docosanoids. The DHA- or eicosapentaenoic acid (EPA)-derived 26 carbon fatty acid is a substrate of elongase ELOVL4, which is expressed in photoreceptor cells and generates very long chain (≥C28) polyunsaturated fatty acids including n-3 (VLC-PUFAs,n-3). While ELOVL4 mutations are linked to vision loss and neuronal dysfunctions, the roles of VLC-PUFAs remain unknown. Here we report a novel class of lipid mediators biosynthesized in human retinal pigment epithelial (RPE) cells that are oxygenated derivatives of VLC-PUFAs,n-3; we termed these mediators elovanoids (ELV). ELVs have structures reminiscent of docosanoids but with different physicochemical properties and alternatively-regulated biosynthetic pathways. The structures, stereochemistry, and bioactivity of ELVs were determined using synthetic materials produced by stereo-controlled chemical synthesis. ELVs enhance expression of pro-survival proteins in cells undergoing uncompensated oxidative stress. Our findings unveil a novel autocrine/paracrine pro-homeostatic RPE cell signaling that aims to sustain photoreceptor cell integrity and reveal potential therapeutic targets for retinal degenerations.
Added entries (persons, corporate bodies, meetings, titles ...)
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Mukherjee, PK
(author)
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Asatryan, A
(author)
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Kautzmann, MA
(author)
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Heap, J
(author)
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Gordon, WC
(author)
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Bhattacharjee, S
(author)
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Yang, R
(author)
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Petasis, NA
(author)
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Bazan, NGKarolinska Institutet
(author)
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Karolinska Institutet
(creator_code:org_t)
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In:Scientific reports: Springer Science and Business Media LLC7:1, s. 5279-2045-2322
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Jun, B
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Mukherjee, PK
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Asatryan, A
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Kautzmann, MA
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Heap, J
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Gordon, WC
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Bhattacharjee, S
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Yang, R
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Petasis, NA
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Bazan, NG
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Karolinska Institutet