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-secretasecleaved soluble amyloid precursor protein (sAPP α ) secretion in relations 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 24 h 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.

Simultaneous Effects of Green Tea Extracts and Fish Oil on Mercury Accumulation and Antioxidant Defenses in Methylmercury-exposed Adult Mice

“…This positive effect of GTE and FO intake may reflect protection against MeHg-mediated oxidative damage. Furthermore, it is reported that EGCG protects neurons by suppressing production of NADPH oxidase-mediated reactive oxygen species and NADPH-d/nNOS expression, and that FO improves the fluidity of synaptic membranes (Wei et al, 2011;He et al, 2011;Suzuki et al, 1998;Yang et al, 2011;Hashimoto et al, 2006). Furthermore, Grotto et al (2011) agree that the protective effects of FO during MeHg exposure may be related to its anti-inflammatory effects.…”

Thioesterase-mediated control of cellular calcium homeostasis enables hepatic ER stress

“…Membrane phospholipids with polyunsaturated fatty acyl chains with 4 or more double bonds have been associated with increased membrane fluidity (34)(35)(36). We investigated the influence of Them2 and PC-TP on the composition of the major ER membrane phospholipids, phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), by mass spectrometry analyses ( Figure 6, C-H).…”

“…ER membranes isolated from livers of Them2 -/-and Pctp -/-mice were enriched with unsaturated membrane phospholipids containing fatty acyl chains with 4 or more double bonds, which markedly increase membrane fluidity (36). Our results further support that the changes in the abundance of ER phospholipids must depend on the activities of enzymes that control fatty acid metabolism (e.g., acyl-CoA synthetases, thioesterases, and desaturases), as opposed to differences in the fatty acid compositions of chow and high-fat diets, which do not contain substantial contents of fatty acids containing 4 or more double bonds.…”

“…Under these conditions, our current findings indicate that the Them2/PC-TP complex facilitates the trafficking of SFAs into the synthesis of glycerolipids, including phospholipids ( Figure 7D). By this molecular mechanism, high-fat diet-induced increases in the acyl chain saturation of ER membrane phospholipids reduce membrane fluidity and alter calcium channel activity (34)(35)(36), leading to the activation of ER stress and gluconeogenic pathways (5,40).…”

Semen Ziziphi Spinosae and Fructus Gardeniae extracts synergistically improve learning and memory of a mouse model

“…Linoleic acid can be transformed in vivo into linolenic and further into arachidonic acid. Linolenic acid is able to increase membrane fluidity and plays an important role in neuron proliferation, nerve conduction and synapse formation (12)(13)(14). Arachidonic acid is one of the most abundant polyunsaturated fatty acids in the body and is essential for maintaining the physical property and function of the membrane (15)(16)(17)(18)(19).…”