NGF blocks polyunsaturated fatty acids biosynthesis in n − 3 fatty acid-supplemented PC12 cells |
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Authors: | Ora Msika Annette Brand Michael A. Crawford Ephraim Yavin |
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Affiliation: | 1. Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, UK;2. Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel |
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Abstract: | Regulation of polyunsaturated fatty acid (PUFA) biosynthesis in proliferating and NGF-differentiated PC12 pheochromocytoma cells deficient in n − 3 docosahexaenoic acid (DHA 22:6n − 3) was studied. A dose- and time-dependent increase in eicosapentaenoic acid (EPA, 20:5n − 3), docosapentaenoic acid (DPA, 22:5n − 3) and DHA in phosphatidylethanolamine (PtdEtn) and phosphatidylserine (PtdSer) glycerophospholipids (GPL) via the elongation/desaturation pathway following alpha-linolenic acid (ALA, 18:3n − 3) supplements was observed. That was accompanied by a marked reduction of eicosatrienoic acid (Mead acid 20:3n − 9), an index of PUFA deficiency. EPA supplements were equally effective converted to 22:5n − 3 and 22:6n − 3. On the other hand, supplements of linoleic acid (LNA, 18:2n − 6) were not effectively converted into higher n − 6 PUFA intermediates nor did they impair elongation/desaturation of ALA. Co-supplements of DHA along with ALA did not interfere with 20:5n − 3 biosynthesis but reduced further elongation to 22-hydrocarbon PUFA intermediates. A marked decrease in the newly synthesized 22:5n − 3 and 22:6n − 3 following ALA or EPA supplements was observed after nerve growth factor (NGF)-induced differentiation. NGF also inhibited the last step in 22:5n − 6 formation from LNA. These results emphasize the importance of overcoming n − 3 PUFA deficiency and raise the possibility that growth factor regulation of the last step in PUFA biosynthesis may constitute an important feature of neuronal phenotype acquisition. |
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Keywords: | ALA, α-linolenic acid (18:3n &minus 3) ARA, arachidonic acid (20:4n &minus 6) DHA, docosahexaenoic acid (22:6n &minus 3) DPA, docosapentaenoic acid (22:5n &minus 3) EPA, eicosapentaenoic acid (20:5n &minus 3) FA, fatty acid FAME, fatty acid methyl ester GC, gas chromatography GPL, glycerophospholipids LNA, linoleic acid (18:2n &minus 6) NGF, nerve growth factor PtdEtn, phosphatidylethanolamine PtdCho, phosphatidylcholine PtdSer, phosphatidylserine PUFA, polyunsaturated fatty acids TLC, thin layer chromatography |
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