Phospholipid species containing long and very long polyenoic fatty acids remain with rhodopsin after hexane extraction of photoreceptor membranes

Aveldaño, Marta I.

doi:10.1021/bi00404a024

Cited by 143 publications

(112 citation statements)

References 34 publications

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“…However, VLC-FA longer than C24 are found in fish, as reported by Aveldaño (1988) who reported the presence of polyene VLC-FA up to C36 in retinal lipids of two fish species. In order to elucidate the molecular mechanisms of VLC-FA biosynthesis in fish, we have focussed on the isolation and characterisation of Elovl4 enzymes from a freshwater model species, zebrafish, the marine teleost cobia, and now the diadromous salmonid, Atlantic salmon.…”

Section: Discussionsupporting

confidence: 65%

Biosynthesis of very long-chain fatty acids (C>24) in Atlantic salmon: Cloning, functional characterisation, and tissue distribution of an Elovl4 elongase

Carmona‐Antoñanzas

Monroig

Dick

et al. 2011

Comparative Biochemistry and Physiology Part B: Biochemistry an

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The elongases of very long-chain fatty acids (Elovl) account for the rate-limiting condensation step of the elongation process in fatty acid (FA) biosynthesis in vertebrates. One member of the Elovl family, Elovl4, has been regarded as a critical enzyme in vertebrates in the production of the so-called very long-chain fatty acids (VLC-FA), a group of compounds that have been scarcely explored in fish. Here we report on the cloning of a novel elovl4-like elongase from Atlantic salmon. The salmon elovl4 cDNA codes for a putative protein KeywordsAquaculture; Atlantic salmon; Elovl4-like elongase; fatty acid biosynthesis; very long-chain fatty acids.3

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Section: Discussionsupporting

confidence: 65%

Biosynthesis of very long-chain fatty acids (C>24) in Atlantic salmon: Cloning, functional characterisation, and tissue distribution of an Elovl4 elongase

Carmona‐Antoñanzas

Monroig

Dick

et al. 2011

Comparative Biochemistry and Physiology Part B: Biochemistry an

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“…We suggest that ELOVL4 protein is a component of an elongase system necessary for the biosynthesis of VLC-PUFA (beyond C26) that are incorporated into ceramides, sphingomyelin, and the sn-1 position of phosphatidylcholine, an activity that has not been established (28,29,37). To explore this possibility, we separated total lipids from 20:5n3-treated Elovl4-transduced cells into individual lipid classes by two-dimensional thin layer chromatography (39) and analyzed the FAME from each class by GC-MS.…”

Section: Resultsmentioning

confidence: 99%

Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids

Agbaga

Brush

Mandal

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

238

346

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Stargardt-like macular dystrophy (STGD3) is a dominantly inherited juvenile macular degeneration that eventually leads to loss of vision. Three independent mutations causing STGD3 have been identified in exon six of a gene named Elongation of very long chain fatty acids 4 (ELOVL4). The ELOVL4 protein was predicted to be involved in fatty acid elongation, although evidence for this and the specific step(s) it may catalyze have remained elusive. Here, using a gain-of-function approach, we provide direct and compelling evidence that ELOVL4 is required for the synthesis of C28 and C30 saturated fatty acids (VLC-FA) and of C28-C38 very long chain polyunsaturated fatty acids (VLC-PUFA), the latter being uniquely expressed in retina, sperm, and brain. Rat neonatal cardiomyocytes and a human retinal epithelium cell line (ARPE-19) were transduced with recombinant adenovirus type 5 carrying mouse Elovl4 and supplemented with 24:0, 20:5n3, or 22:5n3. The 24:0 was elongated to 28:0 and 30:0; 20:5n3 and 22:5n3 were elongated to a series of C28-C38 PUFA. Because retinal degeneration is the only known phenotype in STGD3 disease, we propose that reduced VLC-PUFA in the retinas of these patients may be the cause of photoreceptor cell death.fatty acid biosynthesis ͉ macular degeneration T hree independent mutations in the last exon (exon-VI) of the ELOVL4 gene are associated with dominant Stargardt-like macular dystrophy (STGD3) in humans (1-4). These mutations cause a frame-shift that introduces a stop codon, resulting in premature termination of the protein and removal of the signal sequence for targeting the protein to its putative cellular location, the endoplasmic reticulum (1, 4). As a result, the mutant protein mis-localizes and aggregates (3,5,6), and, when coexpressed with the wild type protein, the mutant and wild-type proteins associate and mis-localize (3, 7). Based on sequence homology with a group of functional yeast genes and other mammalian ELOVLs, the ELOVL4 protein was predicted to be involved in elongation of very long chain fatty acids (1,5,8). For example, the yeast microsomal Elo1p is responsible for elongation of carbon chains between 14:0 and 16:0 (9). Yeast Elo2p and Elo3p, and mammalian ELOVL1, 2, 3, and 5 have been shown to be involved in elongation of saturated, monounsaturated, or polyunsaturated fatty acids (PUFA) from 18 to 26 carbons (10-12). However, a role for ELOVL4 protein in fatty acid elongation and the specific step(s) it may catalyze have remained elusive (13,14). Based on the abundant expression of ELOVL4 protein in photoreceptor cells of the retina (15-17) and to lesser extents in brain, testis, and skin (17), it was first hypothesized that ELOVL4 may be involved in the biosynthetic pathway of docosahexaenoic acid (22:6n3, DHA), the most abundant PUFA in the retina and the brain (1,16,18). A series of experiments carried out in our laboratory (unpublished data) does not support this hypothesis.Recent reports establish ELOVL4 as an essential protein for growth and development, as neonatal ...

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“…However, the relationship between decreased DHA blood supply and disease initiation and progression remains to be ascertained. Moreover, specific structural roles for DHA in photoreceptor outer segments (POS) have been suggested, such as an elongation product of DHA that is found tightly bound to rhodopsin that may favor a membrane organization unlike the classical bilayer (19). The functional significance and the pathological consequences (when peroxidation or shortage in DHA supply occurs) of this DHA elongation product have not been defined.…”

mentioning

confidence: 99%

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Mukherjee

Marcheselli

Vaccari

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

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Photoreceptor cell (rods and cones) renewal is accompanied by intermittent shedding of the distal tips of the outer segment followed by their phagocytosis in the retinal pigment epithelial (RPE) cells. This renewal is essential for vision, and it is thought that it fosters survival of photoreceptors and of RPE cells. However, no specific survival messenger/mediators have as yet been identified. We show here that photoreceptor outer segment (POS) phagocytosis markedly attenuates oxidative stress-induced apoptosis in ARPE-19 cells in culture. This phenomenon does not seem to be a generalized outcome of phagocytosis because nonbiological (polystyrene microsphere) phagocytosis did not elicit protection. The free docosahexaenoic acid (DHA) pool size and neuroprotectin D1 (NPD1) content increased during POS phagocytosis but not during microspheres phagocytosis. We have also explored other lipid mediators [lipoxin A4 and 15(S)-and 12(S)-hydroxyeicosatetraenoic acids] under these conditions and found them unchanged upon POS phagocytosis. Moreover, oxidative stress challenge to RPE cells undergoing POS phagocytosis further increased DHA and NPD1 content. Under these conditions, NPD1 was found within the RPE cells as well as in the culture medium, suggesting autocrine and paracrine bioactivity. Furthermore, using deuterium-labeled DHA, we show that as the availability of free DHA increases during oxidative stress, NPD1 synthesis is augmented in ARPE-19 cells. Our data suggest a distinct signaling that promotes survival of photoreceptor and RPE cells by enhancing the synthesis of NPD1 during phagocytosis. Taken together, NPD1 may be a mediator that promotes homeostatic regulation of cell integrity during photoreceptor cell renewal. docosahexaenoic acid ͉ polystyrene microspheres ͉ retinal pigment epithelial cells ͉ survival ͉ omega-3 fatty acids

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Phospholipid species containing long and very long polyenoic fatty acids remain with rhodopsin after hexane extraction of photoreceptor membranes

Cited by 143 publications

References 34 publications

Biosynthesis of very long-chain fatty acids (C>24) in Atlantic salmon: Cloning, functional characterisation, and tissue distribution of an Elovl4 elongase

Biosynthesis of very long-chain fatty acids (C>24) in Atlantic salmon: Cloning, functional characterisation, and tissue distribution of an Elovl4 elongase

Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

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