The binding of Aβ1-42 to lipid rafts of RBC is enhanced by dietary docosahexaenoic acid in rats: Implicates to Alzheimer's disease.
Once amyloid β peptides (Aβs) 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 Aβ are largely unknown; however, it is very important for the therapeutic target of Aβ-induced hemolysis. In the present study, we investigated whether Aβ1-42 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 Aβ1-42. 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 Aβ1-42. The level of caveolin-1 was augmented in the DRMs of DHA-pretreated rats. Binding between Aβ1-42 and DRMs of RBC significantly increased in DHA-rats. When fluorescently labeled Aβ1-42 (TAMRA-Aβ1-42) 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 Aβs interact with the caveolin-1-rich lipid rafts of DRMs and the interaction is stronger in the DHA-enriched RBCs. The levels of TAMRA-Aβ1-42 also increased in liver DRMs, whereas it decreased in plasma of DHA-pretreated rats. DHA might help clearance of circulating Aβs by increased lipid raft-dependent degradation pathways and implicate to therapies in Alzheimer's disease.
['Hashimoto|Michio|M|', 'Hossain|Shahdat|S|', 'Katakura|Masanori|M|', 'Al Mamun|Abdullah|A|', 'Shido|Osamu|O|']
D000284:Administration, Oral D000544:Alzheimer Disease D000682:Amyloid D016229:Amyloid beta-Peptides D000818:Animals D051242:Caveolin 1 D048430:Cell Shape D002784:Cholesterol D003902:Detergents D004032:Diet D004281:Docosahexaenoic Acids D004912:Erythrocytes D006461:Hemolysis D008099:Liver D008297:Male D021962:Membrane Microdomains D010446:Peptide Fragments D017208:Rats, Wistar D012235:Rhodamines D012996:Solutions D013050:Spectrometry, Fluorescence
Lipid rafts Docosahexaenoic acid Alzheimer's disease Caveolin-1