Attenuated secretion of very low density lipoproteins from McA-RH7777 cells treated with eicosapentaenoic acid is associated with impaired utilization of triacylglycerol synthesized via phospholipid remodeling.
Attenuated secretion of very low density lipoproteins from McA-RH7777 cells treated with eicosapentaenoic acid is associated with impaired utilization of triacylglycerol synthesized via phospholipid remodeling.
复制标题
DOI：
10.1016/j.bbalip.2006.03.018
复制
发表时间：
2006-04
期刊：
影响因子：
--
通讯作者：
K. Tran;Fengcheng Sun;Zheng Cui;G. Thorne‐Tjomsland;Carly St Germain;Louis R. Lapierre;R. McLeod;J. C. Jamieson;Z. Yao
中科院分区：
文献类型：
--
作者：
K. Tran;Fengcheng Sun;Zheng Cui;G. Thorne‐Tjomsland;Carly St Germain;Louis R. Lapierre;R. McLeod;J. C. Jamieson;Z. Yao
在稳定表达人载脂蛋白（apo）B100的McA-RH 7777细胞中，油酸（18：1（n-9））处理促进VLDL的组装和分泌，而二十碳五烯酸（EPA，20：5（n-3））处理减弱VLDL的组装和分泌。在细胞在20%血清存在下培养的条件下，EPA（0.4 mM）对总apoB 100的分泌具有边际效应（通过脉冲追踪分析测定），但降低（50%）三酰甘油（TG）的分泌，表明EPA的抑制效应主要施加在富含TG的VLDL上。通过串联质谱分析磷脂质量和种类，显示EPA处理的细胞中的磷脂酰乙醇胺（PE）增加，在远端高尔基体膜（170%）和内质网（116%）中增加是显着的。脂质脉冲追踪研究显示，含20：5（n-3）和18：1（n-9）的磷脂物质之间存在重大差异，这反过来又与含20：5（n-3）或18：1（n-9）的TG在胞质溶胶和微粒体之间的明显区室化及其在VLDL组装期间的募集相关。因此，18：1-TG作为VLDL分泌，而20：5-TG不是。这些结果表明，EPA衰减极低密度脂蛋白分泌与受损的利用甘油三酯来源于磷脂重塑。
In McA-RH7777 cells stably expressing human apolipoprotein (apo) B100, treatment with oleic acid (18:1(n-9)) promoted whereas treatment with eicosapentaenoic acid (EPA, 20:5(n-3)) attenuated assembly and secretion of VLDL. Under conditions where the cells were cultured in the presence of 20% serum, EPA (0.4 mM) had marginal effect on the secretion of total apoB100 (determined by pulse-chase analysis) but decreased (by 50%) secretion of triacylglycerol (TG), indicating that the inhibitory effect of EPA was exerted primarily on TG-rich VLDL. Analysis of phospholipid mass and species by tandem mass spectrometry showed increased phosphatidylethanolamine (PE) in EPA-treated cells, the increase was significant in the distal Golgi membranes (by 170%) and endoplasmic reticulum (by 116%). Lipid pulse-chase studies showed a major distinction between phospholipid species containing 20:5(n-3) and 18:1(n-9), which in turn was associated with distinct compartmentalization of TG containing 20:5(n-3) or 18:1(n-9) between cytosol and microsomes and their recruitment during VLDL assembly. Thus, 18:1-TG was secreted as VLDL but 20:5-TG was not. These results suggest that EPA attenuation of VLDL secretion is associated with impaired utilization of TG derived from phospholipid remodeling.