title: The binding of Aβ1-42 to lipid rafts of RBC is enhanced by dietary docosahexaenoic acid in rats: Implicates to Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan. Electronic address: michio1@med.shimane-u.ac.jp.
authors.forename: Michio
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan; Department of Biochemistry & Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors.forename: Shahdat
authors.initials: S
authors.lastname: Hossain
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Katakura
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Mamun
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shido
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004032:Diet; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D017208:Rats, Wistar; D012235:Rhodamines / Q000378:metabolism; D012996:Solutions; D013050:Spectrometry, Fluorescence
chemical_list: C114557:5-carboxytetramethylrhodamine succinimidyl ester; D000682:Amyloid; D016229:Amyloid beta-Peptides; D051242:Caveolin 1; D003902:Detergents; D010446:Peptide Fragments; D012235:Rhodamines; D012996:Solutions; C075222:amyloid beta-protein (1-42); D004281:Docosahexaenoic Acids; D002784:Cholesterol
keywords: Alzheimer's disease; Caveolin-1; Docosahexaenoic acid; Lipid rafts