title: NGF blocks polyunsaturated fatty acids biosynthesis in n-3 fatty acid-supplemented PC12 cells.
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.
authors.affiliation: Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, UK.
authors.forename: Ora
authors.initials: O
authors.lastname: Msika
authors.forename: Annette
authors.initials: A
authors.lastname: Brand
authors.forename: Michael A
authors.initials: MA
authors.lastname: Crawford
authors.forename: Ephraim
authors.initials: E
authors.lastname: Yavin
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000172:deficiency; D002454:Cell Differentiation / Q000187:drug effects; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019787:Linoleic Acid / Q000378:metabolism / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000096:biosynthesis; D051381:Rats; D017962:alpha-Linolenic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D009414:Nerve Growth Factors; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D017962:alpha-Linolenic Acid; C483858:phosphatidylethanolamine; C045533:eicosa-5,11,14-trienoic acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid; C026219:docosapentaenoic acid