title: Docosahexaenoic acid reduces amyloid-β(1-42) secretion in human AβPP-transfected CHO-cells by mechanisms other than inflammation related to PGE₂.
abstract: The effect of supplementation with the omega 3 polyunsaturated fatty acid (n3 PUFA) docosahexaenoic acid (DHA) on membrane composition and amyloid-β₁₋₄₂ (Aβ₄₂) secretion was studied in human amyloid-β protein precursor-transfected Chinese Hamster Ovary (CHO) cells. Twenty-four hour incubation with a range of DHA concentrations resulted in a dose-dependent increase in membrane DHA and eicosapentaenoic acid content and a decrease in arachidonic acid content. In addition, DHA supplementation caused a dose-dependent reduction in the secreted Aβ₄₂ levels and resulted in a 4-8 fold decrease in extracellular prostaglandin E₂ (PGE₂) levels. Tocopherol, which was added to DHA to prevent oxidation, may have contributed to the effect of DHA, since it slightly decreased extracellular Aβ₄₂ and PGE₂ levels when given alone. The addition of selective COX2 inhibitors Celebrex and curcumin to the culture medium resulted in a significant and comparable inhibition of PGE₂ release, but did not inhibit Aβ₄₂ secretion, and even significantly increased Aβ₄₂ production in this cell system. Together, the present data show that, whereas both DHA and COX2 inhibitors may reduce PGE₂ production, only DHA in the presence of tocopherol significantly reduced Aβ₄₂ production and concurrently changed membrane lipid composition in CHO cells. It is concluded that in this in vitro setting DHA reduced Aβ₄₂ secretion through membrane-related, but not PGE₂-related mechanisms.
authors.affiliation: Danone Research, Centre For Specialised Nutrition, Wageningen, The Netherlands. martijn.dewilde@danone.com
authors.forename: Martijn C
authors.initials: MC
authors.lastname: de Wilde
authors.forename: Eline M
authors.initials: EM
authors.lastname: van der Beek
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
authors.forename: Inge
authors.initials: I
authors.lastname: Leenders
authors.forename: Almar A M
authors.initials: AA
authors.lastname: Kuipers
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Kamphuis
authors.forename: Laus M
authors.initials: LM
authors.lastname: Broersen
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D004281:Docosahexaenoic Acids; D015232:Dinoprostone