Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism
Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism
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DOI：
10.1160/th13-02-0178
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发表时间：
2014-03-01
影响因子：
6.7
通讯作者：
Rezaee, Farhad
中科院分区：
文献类型：
--
作者：
Dashty, Monireh;Motazacker, Mohammad M.;Rezaee, Farhad
除了在体内转运脂质外，人血浆脂蛋白极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）也被认为是体内蛋白质转移的一种方式，将在炎症和血栓形成中起重要作用的蛋白质从合成部位运送到效应部位。为了更好地了解VLDL和LDL在蛋白质转运中的作用，我们将LTQ ORBITRAP-XL（nLC-MS/MS）与SDS-PAGE凝胶和纯的和确定的VLDL和LDL组分的溶液中胰蛋白酶消化相结合。我们鉴定了95种VLDL相关蛋白和51种LDL相关蛋白的存在，包括所有已知的载脂蛋白和脂质转运蛋白，以及有趣的一组凝血蛋白、补体系统和抗微生物蛋白。凝血酶原、蛋白S、纤维蛋白原γ、PLTP、CETP、CD 14和LBP存在于VLDL上，但不存在于LDL上。异戊酰半胱氨酸氧化酶1、杀皮素、抗菌肽、TFPI-1和纤维蛋白原α链与VLDL和LDL均相关。Apo A-V仅存在于VLDL上，而不存在于LDL上。总的来说，这项研究提供了丰富的知识的蛋白质成分的人血浆脂蛋白系统，并强烈支持的概念，蛋白质穿梭通过这个系统参与调节的生物过程。与VLDL和LDL携带的蛋白质相关的人类疾病可分为三大类：1血脂异常，2动脉粥样硬化和血管疾病，3凝血障碍。
Apart from transporting lipids through the body, the human plasma lipoproteins very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are also thought to serve as a modality for intra-organismal protein transfer, shipping proteins with important roles in inflammation and thrombosis from the site of synthesis to effector locations. To better understand the role of VLDL and LDL in the transport of proteins, we applied a combination of LTQ ORBITRAP-XL (nLC-MS/MS) with both in-SDS-PAGE gel and in-solution tryptic digestion of pure and defined VLDL and LDL fractions. We identified the presence of 95 VLDL- and 51 LDL-associated proteins including all known apolipoproteins and lipid transport proteins, and intriguingly a set of coagulation proteins, complement system and anti- microbial proteins. Prothrombin, protein S, fibrinogen gamma, PLTP, CETP, CD14 and LBP were present on VLDL but not on LDL. Prenylcysteine oxidase 1, dermcidin, cathelicidin antimicrobial peptide, TFPI-1 and fibrinogen alpha chain were associated with both VLDL and LDL. Apo A-V is only present on VLDL and not on LDL. Collectively, this study provides a wealth of knowledge on the protein constituents of the human plasma lipoprotein system and strongly supports the notion that protein shuttling through this system is involved in the regulation of biological processes. Human diseases related to proteins carried by VLDL and LDL can be divided in three major categories: 1 dyslipidaemia, 2 atherosclerosis and vascular disease, and 3 coagulation disorders.