Proteomic characterization of human plasma high density lipoprotein fractionated by gel filtration chromatography.
Proteomic characterization of human plasma high density lipoprotein fractionated by gel filtration chromatography.
复制标题
DOI：
10.1021/pr100520x
复制
发表时间：
2010-10-01
影响因子：
4.4
通讯作者：
Davidson WS
中科院分区：
文献类型：
--
作者：
Gordon SM;Deng J;Lu LJ;Davidson WS
血浆高密度脂蛋白胆固醇（HDL-C）水平与心血管疾病的发病率成反比。现代蛋白质组学技术的最新应用已经鉴定了50种以上与HDL颗粒相关的不同蛋白质，其中许多新发现的蛋白质涉及HDL的非脂质转运过程，包括补体激活，急性期反应和先天免疫。然而，迄今为止，几乎所有基于MS的HDL蛋白质组学研究都在分析前利用密度梯度超离心技术进行HDL分离。这些涉及高剪切力和盐浓度，可以破坏HDL蛋白质相互作用并改变颗粒功能。在这里，我们使用高分辨率尺寸排阻色谱法将正常人血浆分离为17个含磷脂的亚组分。然后，使用磷脂结合树脂，我们通过电喷雾电离质谱法鉴定了与各种大小的脂蛋白相关的蛋白质。我们确定了14个新的磷脂相关蛋白，迁移与传统定义的HDL，其中几个进一步支持HDL在补体调节和蛋白酶抑制作用。这种方法固有的分级分离增加使我们能够以前所未有的分辨率可视化HDL蛋白质在粒度上的分布。所观察到的亚组分的异质性表明HDL颗粒亚群的存在，每个亚群具有不同的蛋白质组分，可以证明赋予不同的生理功能。
Plasma levels of high density lipoprotein cholesterol (HDL-C) are inversely proportional to the incidence of cardiovascular disease. Recent applications of modern proteomic technologies have identified upward of 50 distinct proteins associated with HDL particles with many of these newly discovered proteins implicating HDL in nonlipid transport processes including complement activation, acute phase response and innate immunity. However, almost all MS-based proteomic studies on HDL to date have utilized density gradient ultracentrifugation techniques for HDL isolation prior to analysis. These involve high shear forces and salt concentrations that can disrupt HDL protein interactions and alter particle function. Here, we used high-resolution size exclusion chromatography to fractionate normal human plasma to 17 phospholipid-containing subfractions. Then, using a phospholipid binding resin, we identified proteins that associate with lipoproteins of various sizes by electrospray ionization mass spectrometry. We identified 14 new phospholipid-associated proteins that migrate with traditionally defined HDL, several of which further support roles for HDL in complement regulation and protease inhibition. The increased fractionation inherent to this method allowed us to visualize HDL protein distribution across particle size with unprecedented resolution. The observed heterogeneity across subfractions suggests the presence of HDL particle subpopulations each with distinct protein components that may prove to impart distinct physiological functions.
登录
查看更多内容
影响因子：
29
作者：
Crowe, Seamus;Wu, Lindsay E.;Watt, Matthew J.
通讯作者：
Watt, Matthew J.
影响因子：
14.9
作者：
Keshava Prasad TS;Goel R;Kandasamy K;Keerthikumar S;Kumar S;Mathivanan S;Telikicherla D;Raju R;Shafreen B;Venugopal A;Balakrishnan L;Marimuthu A;Banerjee S;Somanathan DS;Sebastian A;Rani S;Ray S;Harrys Kishore CJ;Kanth S;Ahmed M;Kashyap MK;Mohmood R;Ramachandra YL;Krishna V;Rahiman BA;Mohan S;Ranganathan P;Ramabadran S;Chaerkady R;Pandey A
通讯作者：
Pandey A
影响因子：
3.4
作者：
Karlsson, H;Leanderson, P;Lindahl, M
通讯作者：
Lindahl, M
DOI：
10.1161/01.atv.9.4.538
发表时间：
1989-07-01
期刊：
ARTERIOSCLEROSIS
影响因子：
--
作者：
HOFF, HF;ONEIL, J;JURGENS, G
通讯作者：
JURGENS, G
影响因子：
4.8
作者：
Plotnick, MI;Rubin, H;Schechter, NM
通讯作者：
Schechter, NM