Docosahexaenoic Acid Reduces Amyloid-beta(1-42) Secretion in Human A beta PP-Transfected CHO-Cells by Mechanisms Other than Inflammation Related to PGE(2)

The effect of supplementation with the omega 3 polyunsaturated fatty acid (n-3 PUFA) docosahexaenoic acid (DHA) on membrane composition and amyloid-beta(1-42) (A beta(42)) secretion was studied in human amyloid-beta 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 A beta(42) levels and resulted in a 4-8 fold decrease in extracellular prostaglandin E-2 (PGE(2)) levels. Tocopherol, which was added to DHA to prevent oxidation, may have contributed to the effect of DHA, since it slightly decreased extracellular A beta(42) and PGE(2) levels when given alone. The addition of selective COX-2 inhibitors Celebrex and curcumin to the culture medium resulted in a significant and comparable inhibition of PGE(2) release, but did not inhibit A beta(42) secretion, and even significantly increased A beta(42) production in this cell system. Together, the present data show that, whereas both DHA and COX-2 inhibitors may reduce PGE2 production, only DHA in the presence of tocopherol significantly reduced A beta(42) production and concurrently changed membrane lipid composition in CHO cells. It is concluded that in this in vitro setting DHA reduced A beta(42) secretion through membrane-related, but not PGE(2)-related mechanisms.