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

@article{citeulike:3454463, abstract = {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.}, author = {Agbaga, M. P. and Brush, R. S. and Mandal, M. N. and Henry, K. and Elliott, M. H. and Anderson, R. E.}, citeulike-article-id = {3454463}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0802607105}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18728184}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18728184}, doi = {10.1073/pnas.0802607105}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {elovl4}, month = {September}, number = {35}, pages = {12843--12848}, posted-at = {2008-10-27 23:16:20}, priority = {2}, title = {Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids.}, url = {http://dx.doi.org/10.1073/pnas.0802607105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:3454463 L3 - citeulike-article-id:3454463 N2 - 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. IS - 35 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 1091-6490 EP - 12848 TI - Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids. VL - 105 SP - 12843 KW - elovl4 AU - Agbaga, MP AU - Brush, RS AU - Mandal, MN AU - Henry, K AU - Elliott, MH AU - Anderson, RE PY - 2008/09/02/ UR - http://dx.doi.org/10.1073/pnas.0802607105 ER -