EPA and DHA containing phospholipids have contrasting effects on membrane structure.
EPA and DHA containing phospholipids have contrasting effects on membrane structure.
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DOI：
10.1016/j.jlr.2021.100106
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发表时间：
2021
影响因子：
6.5
通讯作者：
Mason RP
中科院分区：
文献类型：
--
作者：
Sherratt SCR;Juliano RA;Copland C;Bhatt DL;Libby P;Mason RP
Omega-3脂肪酸EPA和DHA影响膜流动性、脂筏和信号转导。一项临床试验，减少心血管事件与伊克沙喷特乙基干预试验，证明高剂量EPA（4 g/d伊克沙喷特乙基）减少复合心血管事件在他汀类药物治疗的高危患者。EPA的益处与治疗水平相关，但使用含DHA制剂的类似试验并未显示事件减少。我们假设不同omega-3 FA制剂的临床疗效差异可能是由于对膜结构的不同影响。为了测试这一点，我们使用小角X射线衍射来比较在具有和不具有1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）和胆固醇的膜中的1-棕榈酰-2-二十碳五烯酰-sn-甘油-3-磷酸胆碱（PL-EPA）、1-棕榈酰-2-二十二碳六烯酰-sn-甘油-3-磷酸胆碱（PL-DHA）和1-棕榈酰-2-花生四烯酰-sn-甘油-3-磷酸胆碱（PL-AA）。使用电子密度分布（电子/μ 3 vs. μ 3）来确定膜结构，包括膜宽度（d-空间）。PL-EPA和PL-DHA在没有POPC和/或胆固醇的情况下具有相似的膜结构，但在POPC和胆固醇的存在下具有相反的效果。PL-EPA在离中心±0-10 μ m的区域内增加膜烃核心电子密度，表明延伸的取向。PL-DHA增加了磷脂头基区域的电子密度，伴随着烃核心的无序和类似的d空间（58 Ω）。添加等摩尔量的PL-EPA和PL-DHA产生的变化与其单独的影响相比减弱。PL-AA使离膜中心±12 μ m处的电子密度增加。PL-EPA、PL-DHA和PL-AA对膜结构的对比效应可能有助于观察到各种omega-3 FA的生物活性和临床作用的差异。
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.
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