de Wilde MC, van der Beek EM, Kiliaan AJ, Leenders I, Kuipers AA, Kamphuis PJ, Broersen LM, de Wilde, Martijn C, van der Beek, Eline M, Kiliaan, Amanda J, Leenders, Inge, Kuipers, Almar A M, Kamphuis, Patrick J, and Broersen, Laus M
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. [ABSTRACT FROM AUTHOR]