title: Estradiol favors the formation of eicosapentaenoic acid (20:5n-3) and n-3 docosapentaenoic acid (22:5n-3) from alpha-linolenic acid (18:3n-3) in SH-SY5Y neuroblastoma cells.
abstract: Whether neurosteroids regulate the synthesis of long chain polyunsaturated fatty acids in brain cells is unknown. We examined the influence of 17-beta-estradiol (E2) on the capacity of SH-SY5Y cells supplemented with alpha-linolenic acid (ALA), to produce eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). Cells were incubated for 24 or 72 h with ALA added alone or in combination with E2 (ALA + E2). Fatty acids were analyzed by gas chromatography of ethanolamine glycerophospholipids (EtnGpl) and phosphatidylcholine (PtdCho). Incubation for 24 h with ALA alone increased EPA and DPA in EtnGpl, by 330 and 430% compared to controls (P < 0.001) and DHA by only 10% (P < 0.05). Although DHA increased by 30% (P < 0.001) in ALA + E2-treated cells, the difference between the ALA and ALA + E2 treatments were not significant after 24 h (Anova-1, Fisher's test). After 72 h, EPA, DPA and DHA further increased in EtnGpl and PtdCho of cells supplemented with ALA or ALA + E2. Incubation for 72 h with ALA + E2 specifically increased EPA (+34% in EtnGpl, P < 0.001) and DPA (+15%, P < 0.001) compared to ALA alone. Thus, SH-SY5Y cells produced membrane EPA, DPA and DHA from supplemental ALA. The formation of DHA was limited, even in the presence of E2. E2 significantly favored EPA and DPA production in cells grown for 72 h. Enhanced synthesis of ALA-elongation products in neuroblastoma cells treated with E2 supports the hypothesis that neurosteroids could modulate the metabolism of PUFA.
authors.affiliation: Unit of Lipid Nutrition and Regulation of Brain Functions, Nu.Re.Li.Ce, INRA, Jouy-en-Josas, France. Jean-Marc.Alessandri@jouy.inra.fr
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alessandri
authors.forename: Audrey
authors.initials: A
authors.lastname: Extier
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Langelier
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Perruchot
authors.forename: Christine
authors.initials: C
authors.lastname: Heberden
authors.forename: Philippe
authors.initials: P
authors.lastname: Guesnet
authors.forename: Monique
authors.initials: M
authors.lastname: Lavialle
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D014407:Tumor Cells, Cultured; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
chemical_list: D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D004958:Estradiol; D015118:Eicosapentaenoic Acid; C026219:docosapentaenoic acid