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标题：EPA and DHA containing phospholipids have contrasting effects on membrane structure
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作者：Samuel C.R. Sherratt ; Rebecca A. Juliano ; Christina Copland 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2021
卷号：62
页码：100106
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl—Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. To test this, we used small-angle X-ray diffraction to compare 1-palmitoyl-2-eicosapentaenoyl-sn-glycero-3-phosphocholine (PL-EPA), 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PL-DHA), and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PL-AA) in membranes with and without 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol. Electron density profiles (electrons/Å3 vs. Å) were used to determine membrane structure, including membrane width (d-space). PL-EPA and PL-DHA had similar membrane structures without POPC and/or cholesterol but had contrasting effects in the presence of POPC and cholesterol. PL-EPA increased membrane hydrocarbon core electron density over an area of ±0–10 Å from the center, indicating an extended orientation. PL-DHA increased electron density in the phospholipid head group region, concomitant with disordering in the hydrocarbon core and a similar d-space (58 Å). Adding equimolar amounts of PL-EPA and PL-DHA produced changes that were attenuated compared with their separate effects. PL-AA increased electron density centered ±12 Å from the membrane center. The contrasting effects of PL-EPA, PL-DHA, and PL-AA on membrane structure may contribute to differences observed in the biological activities and clinical actions of various omega-3 FAs.
关键词：omega-3 FAs;X-ray diffraction;membrane structure;eicosapentaenoic acid;docosahexaenoic;acid;arachidonic acid