Cargando…

Elovanoids are a novel class of homeostatic lipid mediators that protect neural cell integrity upon injury

We report the characterization of a novel class of lipid mediators termed elovanoids (ELVs) (ELV-N32 and ELV-N34), which are dihydroxylated derivatives of 32:6n3 and 34:6n3, respectively. The precursors of ELVs are made by elongation of a 22:6n3 fatty acid and catalyzed by ELOVL4 (elongation of very...

Descripción completa

Detalles Bibliográficos
Autores principales: Bhattacharjee, Surjyadipta, Jun, Bokkyoo, Belayev, Ludmila, Heap, Jessica, Kautzmann, Marie-Audrey, Obenaus, Andre, Menghani, Hemant, Marcell, Shawn J., Khoutorova, Larissa, Yang, Rong, Petasis, Nicos A., Bazan, Nicolas G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617374/
https://www.ncbi.nlm.nih.gov/pubmed/28959727
http://dx.doi.org/10.1126/sciadv.1700735
Descripción
Sumario:We report the characterization of a novel class of lipid mediators termed elovanoids (ELVs) (ELV-N32 and ELV-N34), which are dihydroxylated derivatives of 32:6n3 and 34:6n3, respectively. The precursors of ELVs are made by elongation of a 22:6n3 fatty acid and catalyzed by ELOVL4 (elongation of very-long-chain fatty acids–4). The structure and stereochemistry of ELVs were established using synthetic compounds produced by stereocontrolled total synthesis. We report that ELV-mediated protection is induced in neuronal cultures undergoing either oxygen/glucose deprivation or N-methyl-d-aspartate receptor–mediated excitotoxicity, as well as in experimental ischemic stroke. The methyl ester or sodium salt of ELV-N32 and ELV-N34 resulted in reduced infarct volumes, promoted cell survival, and diminished neurovascular unit disruption when administered 1 hour following 2 hours of ischemia by middle cerebral artery occlusion. Together, our data reveal a novel prohomeostatic and neuroprotective lipid-signaling mechanism aiming to sustain neural cell integrity.