June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The discovery of a new family of lipid mediators, the elovanoids, biosynthesized in human RPE cells
Author Affiliations & Notes
  • Nicolas Guillermo Bazan
    Ophthal & Neuroscience, LSU Health New Orleans , New Orleans, Louisiana, United States
  • Aram Asatryan
    Ophthal & Neuroscience, LSU Health New Orleans , New Orleans, Louisiana, United States
  • Pranab K Mukherjee
    Ophthal & Neuroscience, LSU Health New Orleans , New Orleans, Louisiana, United States
  • Rong Yang
    Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California, United States
  • Nicos Petasis
    Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California, United States
  • Bokkyoo Jun
    Ophthal & Neuroscience, LSU Health New Orleans , New Orleans, Louisiana, United States
  • Footnotes
    Commercial Relationships   Nicolas Bazan, None; Aram Asatryan, None; Pranab Mukherjee, None; Rong Yang, None; Nicos Petasis, None; Bokkyoo Jun, None
  • Footnotes
    Support  Supported by NEI grant EY005121, NIGMS grant GM103340, the Eye, Ear, Nose and Throat Foundation (NGB) and Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1051. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Nicolas Guillermo Bazan, Aram Asatryan, Pranab K Mukherjee, Rong Yang, Nicos Petasis, Bokkyoo Jun; The discovery of a new family of lipid mediators, the elovanoids, biosynthesized in human RPE cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1051.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Docosahexaenoic acid (DHA) elongation in the inner segment of photoreceptors leads to synthesis of very-long-chain polyunsaturated fatty acid (VLC-PUFA) omega-3s (n-3) by ELOVL4. Mutations of this enzyme cause certain forms of retinal degenerations. We found that genetic ablation of adiponectin receptor 1 (AdipoR1) results in retinal degeneration (Rice et al., Nature Comm, 2015) preceded by a remarkable downregulation of the VLC-PUFA omega-3 molecular species of phosphatidylcholine. These observations support our previous hypothesis that VLC-PUFA omega-3s are precursors of novel bioactive mediators. Here we report the identification of 32:6,n-3 and of 34:6,n-3 hydroxylated derivatives, their structural confirmation, and their biological activity in retinal pigment epithelial (RPE) cells.

Methods : Human RPE cells were cultured with 32:6 and 34:6. After cells and media were collected, lipids were extracted and loaded onto a liquid chromatography-mass spectrometer (LC-MS/MS) for analysis. We analyzed fatty acids, precursors of elovanoids (27-hydroxy-FA32:6 and 29–hydroxyl-FA34:6), and elovanoids (20,27-dihydroxy-FA32:6 and 22,29-dihydroxy-FA34:6). Elovanoids were synthesized, and matching with deuterium-labeled derivatives was performed.

Results : Both elovanoids and pre-cursors of elovanoids were detected on the cells under oxidative stress. We used m/z 499 -> 93 and 499 -> 401 MRM transitions for 20,27-dihydroxy-FA32:6, and m/z 527 -> 93 and 527 -> 429 transitions for 22,29-dihydroxy-FA34:6 for detection. For corresponding precursors, we used m/z 483 -> 385 for 27-hydroxy-FA32:6, and m/z 511 -> 413 for 29–hydroxyl-FA34:6. For further identification, we performed full fragmentation on elovanoids and found good matches to the standards.

Conclusions : In RPE cells, VLC-PUFAs (32:6,n-3 and 34:6,n-3) produce derivatives through a lipoxygenation step, and we proposed the name elovanoids. We also identified stable hydroxyl-intermediates of their synthesis. Elovanoids also are released to the extracellular space, therefore they might exert autocrine and paracrine bioactivity. Clearly they are remarkable inducers of cell survival under uncompensated oxidative stress conditions. Thus RPE and photoreceptors undergoing uncompensated oxidative stress, might need elovanoids to contribute to sustaining functional integrity.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×