Molecular speciation and dynamics of oxidized triacylglycerols in lipid droplets: Mass spectrometry and coarse-grained simulations.
Molecular speciation and dynamics of oxidized triacylglycerols in lipid droplets: Mass spectrometry and coarse-grained simulations.
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DOI：
10.1016/j.freeradbiomed.2014.07.042
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发表时间：
2014-11
影响因子：
7.4
通讯作者：
Kagan, Valerian E.
中科院分区：
文献类型：
--
作者：
Mohammadyani, Dariush;Tyurin, Vladimir A.;O'Brien, Matthew;Sadovsky, Yoel;Gabrilovich, Dmitry I.;Klein-Seetharaman, Judith;Kagan, Valerian E.
脂滴（LDs）是一种普遍存在的生理活性细胞器，调节脂质的储存和动员以响应代谢需求。在LD中性脂质的组成成分中，如三酰甘油、胆固醇酯和游离脂肪酸，可氧化的多不饱和分子种类可能相当丰富，但其氧化产物的结构和功能作用尚未研究。我们以前的工作记录了LD中这些过氧化物质的存在。假设亲水性含氧官能团可能会显着改变疏水/亲水分子平衡，在这里，我们利用计算建模来测试的假设，脂质过氧化导致高度疏水性的核心和极性表面（磷酸）脂质单层之间的脂质重新分配的区域丰富的集成酶机械。使用定量液相色谱/质谱，我们的特点是分子形态的oxTAG在LD的树突状细胞在癌症和缺氧滋养层细胞作为两个细胞模型与血脂异常。在许多类型的氧化脂质鉴定，我们发现，氧化截断形式和羟基衍生物的TAG是占主导地位的氧化脂质种类在两种细胞类型的LD。使用粗粒分子动力学（CG-MD）模拟，我们建立了脂质氧化改变了他们的分区，从而氧化脂质迁移到外单层的LD，在那里他们可以影响基本的代谢途径和进行转换，可能导致形成的氧化脂质介质。
Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands. Among the constituent LD neutral lipids, such as triacylglycerols, cholesterol esters, and free fatty acids, oxidizable polyunsaturated molecular species may be quite abundant, yet the structural and functional roles of their oxidation products have not been studied. Our previous work documented the presence of these peroxidized species in LDs. Assuming that hydrophilic oxygen-containing functionalities may markedly change the hydrophobic/hydrophilic molecular balance, here we utilized computational modeling to test the hypothesis that lipid peroxidation causes redistribution of lipids between the highly hydrophobic core and the polar surface (phospho) lipid monolayer–the area enriched with integrated enzymatic machinery. Using quantitative liquid chromatography/mass spectrometry, we characterized molecular speciation of oxTAGs in LDs of dendritic cells in cancer and hypoxic trophoblasts cells as two cellular models associated with dyslipidemia. Among the many types of oxidized lipids identified, we found that oxidatively truncated forms and hydroxyl derivatives of TAGs were the prevailing oxidized lipid species in LDs in both cell types. Using coarse grained molecular dynamics (CG-MD) simulations we established that lipid oxidation changed their partitioning whereby oxidized lipids migrated into the outer monolayer of the LD, where they can affect essential metabolic pathways and undergo conversions, possibly leading to the formation of oxygenated lipid mediators.
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影响因子：
2.3
作者：
Fujimoto, Toyoshi;Ohsaki, Yuki;Cheng, Jinglei;Suzuki, Michitaka;Shinohara, Yuki
通讯作者：
Shinohara, Yuki
影响因子：
1.9
作者：
Malone, M;Evans, JJ
通讯作者：
Evans, JJ
影响因子：
4.5
作者：
Puskás LG;Fehér LZ;Vizler C;Ayaydin F;Rásó E;Molnár E;Magyary I;Kanizsai I;Gyuris M;Madácsi R;Fábián G;Farkas K;Hegyi P;Baska F;Ozsvári B;Kitajka K
通讯作者：
Kitajka K
DOI：
10.1016/s0002-9378(99)70661-7
发表时间：
1999-04-01
影响因子：
9.8
作者：
Nelson, DM;Johnson, RD;Sadovsky, Y
通讯作者：
Sadovsky, Y
癌症中的脂质积累和树突状细胞功能障碍
影响因子：
82.9
作者：
Herber, Donna L.;Cao, Wei;Gabrilovich, Dmitry I.
通讯作者：
Gabrilovich, Dmitry I.