Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity

Abstract 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 ver...

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Autores principales:	Bokkyoo Jun, Pranab K. Mukherjee, Aram Asatryan, Marie-Audrey Kautzmann, Jessica Heap, William C. Gordon, Surjyadipta Bhattacharjee, Rong Yang, Nicos A. Petasis, Nicolas G. Bazan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78f8ad6d48ad4ead8958b0ab446f4c81
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spelling	oai:doaj.org-article:78f8ad6d48ad4ead8958b0ab446f4c812021-12-02T16:06:07ZElovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity10.1038/s41598-017-05433-72045-2322https://doaj.org/article/78f8ad6d48ad4ead8958b0ab446f4c812017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05433-7https://doaj.org/toc/2045-2322Abstract 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.Bokkyoo JunPranab K. MukherjeeAram AsatryanMarie-Audrey KautzmannJessica HeapWilliam C. GordonSurjyadipta BhattacharjeeRong YangNicos A. PetasisNicolas G. BazanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bokkyoo Jun Pranab K. Mukherjee Aram Asatryan Marie-Audrey Kautzmann Jessica Heap William C. Gordon Surjyadipta Bhattacharjee Rong Yang Nicos A. Petasis Nicolas G. Bazan Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
description	Abstract 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.
format	article
author	Bokkyoo Jun Pranab K. Mukherjee Aram Asatryan Marie-Audrey Kautzmann Jessica Heap William C. Gordon Surjyadipta Bhattacharjee Rong Yang Nicos A. Petasis Nicolas G. Bazan
author_facet	Bokkyoo Jun Pranab K. Mukherjee Aram Asatryan Marie-Audrey Kautzmann Jessica Heap William C. Gordon Surjyadipta Bhattacharjee Rong Yang Nicos A. Petasis Nicolas G. Bazan
author_sort	Bokkyoo Jun
title	Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
title_short	Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
title_full	Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
title_fullStr	Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
title_full_unstemmed	Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
title_sort	elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/78f8ad6d48ad4ead8958b0ab446f4c81
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Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity

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