Article

Polyunsaturated Eicosapentaenoic Acid Displaces Proteins from Membrane Rafts by Altering Raft Lipid Composition

Department of Internal Medicine III, University of Vienna, A-1090 Vienna, Austria.
Journal of Biological Chemistry (Impact Factor: 4.57). 11/2001; 276(40):37335-40. DOI: 10.1074/jbc.M106193200
Source: PubMed

ABSTRACT

Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (20:5 (n-3)) inhibit T lymphocyte activation probably by displacing acylated signaling proteins from membrane lipid rafts. Under physiological conditions, saturated fatty acyl residues of such proteins partition into the cytoplasmic membrane lipid leaflet with high affinity for rafts that are enriched in saturated fatty acyl-containing lipids. However, the biochemical alteration causing displacement of acylated proteins from rafts in PUFA-treated T cells is still under debate but could principally be attributed to altered protein acylation or changes in raft lipid composition. We show that treatment of Jurkat T cells with polyunsaturated eicosapentaenoic acid (20:5 (n-3)) results in marked enrichment of PUFAs (20:5; 22:5) in lipids from isolated rafts. Moreover, PUFAs were significantly incorporated into phosphatidylethanolamine that predominantly resides in the cytoplasmic membrane lipid leaflet. Notably, palmitate-labeled Src family kinase Lck and the linker for activation of T cells (LAT) were both displaced from lipid rafts indicating that acylation by PUFAs is not required for protein displacement from rafts in PUFA-treated T cells. In conclusion, these data provide strong evidence that displacement of acylated proteins from rafts in PUFA-treated T cells is predominantly due to altered raft lipid composition.

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    • "Recently, it has been suggested a role for ω-3 PUFAs in reorganizing the composition of the mitochondrial membrane, while promoting improvements in ADP sensitivity, determined as mitochondrial responses during ADP titration (Herbst et al., 2014). Moreover, it is well known that saturated FA incorporation reduces membrane fluidity, whereas PUFA do not have such effect (Clamp et al., 1997;Stulnig et al., 2001;Holzer et al., 2011). Further studies are needed to elucidate these mechanisms. "
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    • "This indicates that, at the sn-1 position of phospholipids, a 18:1 fatty acid is not, while a 16:0 or 18:0 fatty acid is, favorable for inclusion in DRMs. The data of Stulnig et al. (2001) show a similar enrichment of 16:0 and 18:0 fatty acids in the DRM fraction of Jurkat T cells, while 16:1 and 18:1 fatty acids were excluded from DRMs. Unfortunately, the position of the fatty acids was not determined. "
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    • "One recent in vivo study demonstrated that a small fraction of n-3 PUFAs from dietary fish oil incorporated into sphingolipids of murine B cells (Rockett et al., 2012). These results were consistent with similar findings in cell culture with immortal T cells (Stulnig et al., 2001). A fourth possibility we propose is that n-3 PUFA acyl chains could become esterified to cholesterol to modify Figure 2 Potential mechanisms by which n-3 PUFAs could disrupt lipid microdomain distribution. "
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