Docosahexaenoic acid affects cell signaling by altering lipid rafts

Abstract

-With 22 carbons and 6 double bonds docosahexaenoic acid (DHA) is the longest and most unsaturated fatty acid commonly found in membranes. It represents the extreme example of a class of important human health promoting agents known as omega-3 fatty acids. DHA is particularly abundant in retinal and brain tissue, often comprising about 50% of the membrane's total acyl chains. Inadequate amounts of DHA have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities to depression and suicide. The molecular mode of action of DHA, while not yet understood, has been the focus of our research. Here we briefly summarize how DHA affects membrane physical properties with an emphasis on membrane signaling domains known as rafts. We report the uptake of DHA into brain phosphatidylethanolamines and the subsequent exclusion of cholesterol from the DHA-rich membranes. We also demonstrate that DHA-induced apoptosis in MDA-MB-231 breast cancer cells is associated with externalization of phosphatidylserine and membrane disruption ("blebbing"). We conclude with a proposal of how DHA incorporation into membranes may control cell biochemistry and physiology. apoptosis / docosahexaenoic acid / lipid rafts / membranes / phospholipids

The location and behavior of α‐tocopherol in membranes

“…With 22 carbons and 6 double bonds, docosahexaenoic acid (DHA) is the most unsaturated PUFA commonly found in biological membranes [46] and so would be an ideal candidate for a-tocopherol association studies. We [47][48][49], as do others [50,51], attribute the efficacy of DHA in preventing numerous human afflictions in part to the formation of DHA-rich, non-raft domains from which cholesterol is excluded. The tremendous disorder of PUFA chains is responsible for the aversion cholesterol has for DHA-containing phospholipids [48,49].…”

Baclofen, raclopride, and naltrexone differentially reduce solid fat emulsion intake under limited access conditions

“…It is possible that GABA B actions potentially affected by fat consumption (e.g. altered association with lipid rafts; Becker, et al, 2001;Koyrakh, et al, 2005;Stillwell, et al, 2005) require a certain threshold level of weekly fat intake. In addition, the present study involved consumption of a large quantity of emulsion in a relatively short period of time (1 hour).…”

Docosahexaenoic Acid (DHA), in the Prevention and Treatment of Neurodegenerative Diseases

“…Their role in the fluidity of the neuronal membrane appears as one of the most relevant attributes (Saiz & Klein, 2001). In fact, up to day the classification of membrane fluidity is based on the level of DHA present in the phospholipids that form the membrane matrix (Stillwell et al, 2005). However, the higher fluidity that confers DHA to neuronal membrane is not sufficient to explain the neuroprotective effects attributed to the fatty acid.…”

“…However, the higher fluidity that confers DHA to neuronal membrane is not sufficient to explain the neuroprotective effects attributed to the fatty acid. As result of multiple investigations, it has been established that acylation of DHA at the sn-2 position in the membrane phospholipids and the activity of PLA-2, are additional features of DHA, by itself, to achieve an additional neuroprotective action of the fatty acid against certain cytotoxic situations, as are neurodegenerative diseases (Stillwell et al, 2005;Brown & London, 2000). It is no casual that DHA is present mainly at the sn-2 position in the phospholipids of neuronal membranes (48% in phosphatidylcholine, 52% in fosfatidilserine and 20% in phosphatidylethanolamine) (Aveldano & Bazan, 1983).…”