title: Effects of fatty acid unsaturation numbers on membrane fluidity and α-secretase-dependent amyloid precursor protein processing.
abstract: Fatty acids may integrate into cell membranes to change physical properties of cell membranes, and subsequently alter cell functions in an unsaturation number-dependent manner. To address the roles of fatty acid unsaturation numbers in cellular pathways of Alzheimer's disease (AD), we systematically investigated the effects of fatty acids on cell membrane fluidity and α-secretase-cleaved soluble amyloid precursor protein (sAPP(α)) secretion in relation to unsaturation numbers using stearic acid (SA, 18:0), oleic acid (OA, 18:1), linoleic acid (LA, 18:2), α-linolenic acid (ALA, 18:3), arachidonic acid (AA, 20:4), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6). Treatments of differentiated human neuroblastoma (SH-SY5Y cells) with AA, EPA and DHA for 24h increased sAPP(α) secretion and membrane fluidity, whereas those treatments with SA, OA, LA and ALA did not. Treatments with AA and DHA did not alter the total expressions of amyloid precursor protein (APP) and α-secretases in SH-SY5Y cells. These results suggested that not all unsaturated fatty acids but only those with 4 or more double bonds, such as AA, EPA and DHA, are able to increase membrane fluidity and lead to increase in sAPP(α) secretion. This study provides insights into dietary strategies for the prevention of AD.
authors.affiliation: Department of Biological Engineering, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Yang
authors.forename: Wenwen
authors.initials: W
authors.lastname: Sheng
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
authors.forename: James C-M
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy / Q000201:enzymology / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D045744:Cell Line, Tumor; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D046188:Protein Modification, Translational / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D053829:Amyloid Precursor Protein Secretases