The binding of A beta(1-42) to lipid rafts of RBC is enhanced by dietary docosahexaenoic acid in rats: Implicates to Alzheimer's disease

摘要

Once amyloid beta peptides (A beta s) of the Alzheimer's disease build up in blood circulation, they are capable of binding to red blood cell (RBC) and inducing hemolysis of RBC. The mechanisms of the interactions between RBC and A beta are largely unknown; however, it is very important for the therapeutic target of A beta-induced hemolysis. In the present study, we investigated whether A beta(1-42) interacts with caveolin-1-containing detergent-resistant membranes (DRMs) of RBC and whether the interaction could be modulated by dietary pre-administration of docosahexaenoic acid (DHA). DHA pre-administration to rats inhibited hemolysis by A beta(1-42). This activity was accompanied by increased DHA levels and membrane fluidity and decreased cholesterol level, lipid peroxidation, and reactive oxygen species in the RBCs of the DHA-pretreated rats, suggesting that the antioxidative property of DHA may rescue RBCs from oxidative damage by A beta(1-42). The level of caveolin-1 was augmented in the DRMs of DHA-pretreated rats. Binding between A beta(1-42) and DRMs of RBC significantly increased in DHA-rats. When fluorescently labeled A beta(1-42) (TAMRA-A beta(1-42)) was directly infused into the bloodstream, it again occupied the caveolin-1-containing DRMs of the RBCs from the DHA-rats to a greater extent, indicating that circulating A beta s interact with the caveolin-1-rich lipid rafts of DRMs and the interaction is stronger in the DHA-enriched RBCs. The levels of TAMRA-A beta(1-42) also increased in liver DRMs, whereas it decreased in plasma of DHA-pretreated rats. DHA might help clearance of circulating A beta s by increased lipid raft-dependent degradation pathways and implicate to therapies in Alzheinier's disease. (C) 2015 Elsevier B.V. All rights reserved.