ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3[S]
- Man Yu†,**,
- Aaron Benham*,§,
- Sreemathi Logan*,†§,
- R. Steven Brush*,§,
- Md Nawajes A. Mandal*,§,
- Robert E. Anderson*,†§ and
- Martin-Paul Agbaga1,*,§
- *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
- **Ophthalmic Laboratories and Department of Ophthalmology, West China Hospital, Sichuan University, P. R. China
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.
- elongase of very long chain fatty acids
- very long chain polyunsaturated fatty acids
- chylomicrons
- fatty acids/biosynthesis
- juvenile autosomal dominant Stargardt-like macular dystrophy type 3 disease
- arachidonic acid
- fish oil
Footnotes
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↵1 To whom correspondence should be addressed. e-mail: martin-paul-agbaga{at}ouhsc.edu
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- Abbreviations:
- AA
- arachidonic acid
- AMD
- age-related macular degeneration
- AREDS
- Age-Related Eye Disease Study
- DHA
- docosahexaenoic acid
- EPA
- eicosapentaenoic acid
- ELOVL4
- ELOngase of very long chain fatty acid-4
- FAME
- fatty acid methyl ester
- FID
- flame ionization detector
- GC
- gas chromatograph
- LA
- linoleic acid
- LC-PUFA
- long-chain PUFA
- PC
- phosphatidylcholine
- PC12
- pheochromocytoma cell
- pfu
- plaque-forming units
- qRT-PCR
- quantitative real-time PCR
- RPE
- retinal pigment epithelium
- SIM
- single-ion monitoring
- STGD3
- autosomal dominant Stargardt-like macular dystrophy
- VLC-FA
- very long chain saturated or monounsaturated fatty acid
- VLC-PUFA
- very long chain PUFA
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This work was supported by National Institutes of Health, National Eye Institute, Grants EY-04149, EY-00871, and EY-12190 (R.E.A.); National Center for Research Resources Grant RR-17703 (R.E.A.); grants from Research to Prevent Blindness, Inc. and the Foundation Fighting Blindness (R.E.A.); and from the Hope for Vision and Knights Templar Eye Foundation, Inc. (M.P.A.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
-
↵[S] The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one figure.
- Received October 11, 2011.
- Revision received December 5, 2011.
- Copyright © 2012 by the American Society for Biochemistry and Molecular Biology, Inc.
