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Elovanoids are nove...
Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
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Jun, B (author)
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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, NG (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-07-13
- 2017
- English.
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 5279-
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Abstract
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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.
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- By the author/editor
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Jun, B
-
Mukherjee, PK
-
Asatryan, A
-
Kautzmann, MA
-
Heap, J
-
Gordon, WC
-
show more...
-
Bhattacharjee, S
-
Yang, R
-
Petasis, NA
-
Bazan, NG
-
show less...
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Scientific repor ...
- By the university
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Karolinska Institutet