Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
Open accessAbstract
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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ELVs and their precursors were detected in neuronal cultures under OGD stress.
“ELVs and their precursors were detected in neuronal cultures under OGD stress (Jun et al., 2017).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Jun et al., 2017
These ≥ 28 carbons VLC fatty acids are critical to brain function.
“These ≥ 28 carbons VLC fatty acids are critical to brain function (Bhattacharjee et al., 2017; Demaerschalk et al., 2016; Jun et al., 2017; Poulin et al., 2016; Rau et al., 2012; Tasca et al., 2015; Tasic et al., 2016; Zeisel et al., 2015; Zhang et al., 2014).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Jun et al., 2017
ELV availability is abolished in the retinas of mice with genetically ablated AdipoR1.
“ELV availability is abolished in the retinas of mice with genetically ablated AdipoR1 (Jun et al., 2017).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Jun et al., 2017
The structure and stereochemistry of ELV-N32 and ELV-N34 was established.
“The structure and stereochemistry of ELVs with 32 and 34 carbons (ELV-N32, ELV-N34) was established (Bhattacharjee et al., 2017; Jun et al., 2017).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Jun et al., 2017
ELVs biosynthesis in human RPE cells is activated during UOS, targeting pro-homeostatic functions to preserve PRC integrity.
“ELVs biosynthesis in human RPE cells is activated during UOS (Jun et al., 2017) targeting pro-homeostatic functions to preserve PRC integrity.”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Jun et al., 2017
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- Authors
- Jun, B., Mukherjee, P. K., Asatryan, A., Kautzmann, M.-A., Heap, J., Gordon, W. C., Bhattacharjee, S., Yang, R., Petasis, N. A., & Bazan, N. G.
- Affiliations
- Louisiana State University (US)
- University of Southern California (US)
- Corresponding author
- Bazan, Nicolas G.
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-07-13
- Volume
- 7
- Issue
- 1
- Pages
- 5279-5279
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5509689
- OpenAlex
- W2729615630
- Cited by
- 80
- References
- 70
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 14 · 2022: 7 · 2021: 12 · 2020: 9 · 2019: 10 · 2018: 11 · 2017: 3
- FWCI
- 7.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Research to Prevent Blindness
- National Eye Institute (R01EY005121)
- National Institute of General Medical Sciences (GM-103340, P30GM103340)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- docosanoids, very long chain polyunsaturated fatty acids, ELOVL4, retinal pigment epithelium, neuroprotection, oxidative stress, autocrine and paracrine signaling, retinal degeneration, docosahexaenoic acid, eicosapentaenoic acid, lipid mediators
- MeSH terms
- Neuroprotection, Adult, Animals, Cells, Cultured, Eye Proteins, Fatty Acids, Unsaturated, Humans, Male, Membrane Proteins, Mice, Inbred C57BL, Photoreceptor Cells, Signal Transduction, Mice, Knockout, Oxidative Stress, Neuroprotective Agents, Receptors, Adiponectin, Retinal Pigment Epithelium, Young Adult
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