title: ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3.
abstract: We hypothesized that reduction/loss of very long chain PUFAs (VLC-PUFAs) due to mutations in the ELOngase of very long chain fatty acid-4 (ELOVL4) protein contributes to retinal degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3) and age-related macular degeneration; hence, increasing VLC-PUFA in the retina of these patients could provide some therapeutic benefits. Thus, we tested the efficiency of elongation of C20-C22 PUFA by the ELOVL4 protein to determine which substrates are the best precursors for biosynthesis of VLC-PUFA. The ELOVL4 protein was expressed in pheochromocytoma cells, while green fluorescent protein-expressing and nontransduced cells served as controls. The cells were treated with 20:5n3, 22:6n3, and 20:4n6, either individually or in equal combinations. Both transduced and control cells internalized and elongated the supplemented FAs to C22-C26 precursors. Only ELOVL4-expressing cells synthesized C28-C38 VLC-PUFA from these precursors. In general, 20:5n3 was more efficiently elongated to VLC-PUFA in the ELOVL4-expressing cells, regardless of whether it was in combination with 22:6n3 or with 20:4n6. In each FA treatment group, C34 and C36 VLC-PUFAs were the predominant VLC-PUFAs in the ELOVL4-expressing cells. In summary, 20:5n3, followed by 20:4n6, seems to be the best precursor for boosting the synthesis of VLC-PUFA by ELOVL4 protein.
authors.affiliation: Departments of Ophthalmology and Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Ophthalmic Laboratories and Department of Ophthalmology, West China Hospital, Sichuan University, P. R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Yu
authors.affiliation: Departments of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Dean McGee Eye Institute, Oklahoma City, OK; and.
authors.forename: Aaron
authors.initials: A
authors.lastname: Benham
authors.affiliation: Departments of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Departments of Ophthalmology and Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Dean McGee Eye Institute, Oklahoma City, OK; and.
authors.forename: Sreemathi
authors.initials: S
authors.lastname: Logan
authors.affiliation: Departments of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Dean McGee Eye Institute, Oklahoma City, OK; and.
authors.forename: R Steven
authors.initials: RS
authors.lastname: Brush
authors.affiliation: Departments of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Dean McGee Eye Institute, Oklahoma City, OK; and.
authors.forename: Md Nawajes A
authors.initials: MNA
authors.lastname: Mandal
authors.affiliation: Departments of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Departments of Ophthalmology and Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Dean McGee Eye Institute, Oklahoma City, OK; and.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Anderson
authors.affiliation: Departments of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Dean McGee Eye Institute, Oklahoma City, OK; and. Electronic address: martin-paul-agbaga@ouhsc.edu.
authors.forename: Martin-Paul
authors.initials: MP
authors.lastname: Agbaga
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D015153:Blotting, Western; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016716:PC12 Cells; D051381:Rats
chemical_list: C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; D016718:Arachidonic Acid; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases