NGF blocks polyunsaturated fatty acids biosynthesis in n 鈭?#xa0;3 fatty acid-supplemented PC12 cells

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• 作者：Ora Msika^a ; Annette Brand^a ; Michael A. Crawford^a ; Ephraim Yavin^a ; ^b ; ^{ephraim.yavin@weizmann.ac.il}
• 关键词：ALA ; 伪-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  ; &m
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2012
• 期刊代码：18_13881981
• 类别：bio
• 出版时间：July, 2012
• 卷：1821
• 期：7
• 页码：1022-1030
• 文件大小：1037 K

摘要

Regulation of polyunsaturated fatty acid (PUFA) biosynthesis in proliferating and NGF-differentiated PC12 pheochromocytoma cells deficient in n 鈭?#xA0;3 docosahexaenoic acid (DHA 22:6n 鈭?#xA0;3) was studied. A dose- and time-dependent increase in eicosapentaenoic acid (EPA, 20:5n 鈭?#xA0;3), docosapentaenoic acid (DPA, 22:5n 鈭?#xA0;3) and DHA in phosphatidylethanolamine (PtdEtn) and phosphatidylserine (PtdSer) glycerophospholipids (GPL) via the elongation/desaturation pathway following alpha-linolenic acid (ALA, 18:3n 鈭?#xA0;3) supplements was observed. That was accompanied by a marked reduction of eicosatrienoic acid (Mead acid 20:3n 鈭?#xA0;9), an index of PUFA deficiency. EPA supplements were equally effective converted to 22:5n 鈭?#xA0;3 and 22:6n 鈭?#xA0;3. On the other hand, supplements of linoleic acid (LNA, 18:2n 鈭?#xA0;6) were not effectively converted into higher n 鈭?#xA0;6 PUFA intermediates nor did they impair elongation/desaturation of ALA. Co-supplements of DHA along with ALA did not interfere with 20:5n 鈭?#xA0;3 biosynthesis but reduced further elongation to 22-hydrocarbon PUFA intermediates. A marked decrease in the newly synthesized 22:5n 鈭?#xA0;3 and 22:6n 鈭?#xA0;3 following ALA or EPA supplements was observed after nerve growth factor (NGF)-induced differentiation. NGF also inhibited the last step in 22:5n 鈭?#xA0;6 formation from LNA. These results emphasize the importance of overcoming n 鈭?#xA0;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.