COMPOSITION OF HIGH DENSITY LIPOPROTEIN SUBCLASSES

高密度脂蛋白亚类的组成

• 批准号: 7601817
• 负责人: JOHN P KANE
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601817
• 关键词: Age-Years; Antiatherogenic; Antibodies; Antibody Specificity; Apolipoprotein E; Atherosclerosis; Blindness; Cells; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Coronary Arteriosclerosis; Funding; Grant; High Density Lipoproteins; Human; Indium; Individual; Institution; Laboratories; Lipids; Lipoproteins; Macular degeneration; Mass Spectrum Analysis; Mediating; Metabolic; Metabolism; Methods; Molecular; Plasma; Play; Protease Inhibitor; Proteins; Research; Research Personnel; Resources; Retinal; Role; Source; Structure of retinal pigment epithelium; Transfer Factor; Transferase; United States National Institutes of Health; Western Blotting; hepatic lipase; insight; lipid metabolism; lipid transport; particle; phosphatidylcholine transfer protein

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our studies of lipoprotein metabolism, in particular, the high density lipoproteins (HDL) offer unique insights into lipid metabolism and transport that will be of value in understanding atherosclerosis at a molecular level. Methods developed in our laboratory have allowed us to document previously unreported molecular subspecies of HDL, each of which may play a specific antiatherogenic role associated with HDL. HDL subspecies purified from plasmas of normo- and dyslipidemic subjects reveal a variety of proteins. To date we have identified fifty-three candidate proteins that associate with discrete HDL particles. Among these , we have also discovered a new protein, designated apoL-1, that is associated with two discrete HDL species. While protein compositions of some HDL subspecies have been identified by Western blotting, we seek to obtain unequivocal characterization by mass spectroscopy especially in cases were our antibodies produce questionable identities. This frequently results from poor antibody specificity and recognition. Mass spectroscopic identification is of most benefit for the identification of proteins for which we have no specific antibodies, for proteins of low concentration, and for proteins which are not generally considered to associate with HDL. Our understanding of the HDL protein components consisting of lipid transfer factors such as cholesterol transfer protein, lecithin:cholesterol transferase, phosholipid transfer protein, hepatic lipase, plasma protease inhibitors, apoE, apoAIV, and apoL is paramount to our ability to understand the metabolic function of HDL-mediated protection in coronary artery disease. We have now begun to study the role of lipid transport in the retinal pigment epithelial cells, because they are key elements in human macular degeneration, the major cause of blindness in individuals over fifty years of age. This involves the identification of proteins expressed by the retinal cells, using mass spectrometry.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们对脂蛋白代谢，特别是高密度脂蛋白（HDL）的研究提供了对脂质代谢和转运的独特见解，这将对在分子水平上理解动脉粥样硬化具有价值。我们实验室开发的方法使我们能够记录以前未报道的HDL分子亚种，每种分子亚种都可能发挥与HDL相关的特定抗动脉粥样硬化作用。 从正常和血脂异常受试者的血浆中纯化的HDL亚种揭示了多种蛋白质。到目前为止，我们已经确定了53个候选蛋白与离散HDL颗粒。其中，我们还发现了一种新的蛋白质，命名为apoL-1，这是与两个离散的HDL物种。虽然一些HDL亚种的蛋白质组成已通过Western印迹法鉴定，但我们寻求通过质谱法获得明确的表征，特别是在我们的抗体产生可疑身份的情况下。这通常是由于抗体特异性和识别能力差造成的。质谱鉴定对于鉴定我们没有特异性抗体的蛋白质、低浓度蛋白质和通常认为与HDL无关的蛋白质是最有益的。我们对HDL蛋白组分的理解，包括脂质转移因子，如胆固醇转移蛋白，卵磷脂：胆固醇转移酶，磷脂转移蛋白，肝脂肪酶，血浆蛋白酶抑制剂，载脂蛋白E，载脂蛋白AIV，和载脂蛋白L是至关重要的，我们有能力了解HDL介导的保护冠状动脉疾病的代谢功能。 我们现在已经开始研究脂质转运在视网膜色素上皮细胞中的作用，因为它们是人类黄斑变性的关键因素，黄斑变性是50岁以上个体失明的主要原因。 这涉及使用质谱法鉴定视网膜细胞表达的蛋白质。