DYNAMICS OF APOE BINDING TO LIPOPROTEINS AND RECEPTORS
APOE 与脂蛋白和受体结合的动力学
基本信息
- 批准号:3366035
- 负责人:
- 金额:$ 16.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-04-01 至 1998-03-31
- 项目状态:已结题
- 来源:
- 关键词:apolipoproteins blood lipoprotein blood lipoprotein biosynthesis blood lipoprotein transport cell type complementary DNA fatty acylation glycosylation human subject intracellular transport laboratory rabbit laboratory rat liver cells posttranslational modifications protein structure function radioimmunoassay radiotracer receptor binding site directed mutagenesis species difference thrombin transfection very low density lipoprotein western blottings
项目摘要
ApoE is found in a number of animal species and although it is
synthesized by various cell types, most plasma apoE is produced by the
liver. In the circulation, apoE participates in lipid transport by
mediating lipoprotein binding to the B/E receptor. A key factor in
plasma lipid transport is the capacity of apoE to exchange between
lipoprotein surfaces; however, not all apoE is capable of transfer, and
not all lipoprotein-associated apoE is receptor active. The factors
which govern apoE transfer between lipoproteins and receptor binding
capacity are unclear. Two lines of evidence demonstrate that apoE
secreted by the liver may be modified by fatty acid acylation. Whether
this acylation is related to the functional state of plasma apoE is not
known. Recently it has been suggested that a portion of the apoE
synthesized by hepatic cells is not secreted, but remains within the cell
where it may participate in intracellular lipid transport. The signal
which determines whether apoE is secreted or remains in the cell is
undefined, however, in other systems, targeting of proteins to specific
cellular sites is accomplished by fatty acid acylation. The possibility
that fatty acid acylation of apoE might affect its functional capacities
in the plasma and/or its trafficking within the cell is intriguing. The
goal of this project is to understand the factors which affect apoE
transferability and receptor binding capacity and control targeting of
apoE to intra- and extracellular pools. This goal will be accomplished
through four aims designed to examine the existence and origins of
different physical states of apoE and to probe their influence on apoE
functional capacity. First, the physical and physiological state of the
apoE component of nascent VLDL (isolated from the liver) will be examined
by determining the susceptibility of apoE to thrombin cleavage, the
capacity of apoE to transfer off of VLDL, and the capacity of apoE to
mediate binding of nascent VLDL to the B/E receptor. The second aim is
to examine fatty acid acylation of apoE and determine the appearance of
apoE acylation in differing cell types and animal species, the
localization of acyl-apoE in a specific lipoprotein class, the fatty acid
specificity and site(s) of acylation, and the physical and physiological
consequences of apoE acylation. The third aim is to examine cellular
aspects of apoE acylation and determine the role of acylation in
targeting of apoE to intra- and extracellular pools, the temporal
relationship of apoE acylation to protein synthesis and
post-translational modifications, and factors which influence apoE
acylation. Finally, site-directed mutagenesis will be used to modify the
acylation site(s) of apoE, and the cDNA will be transfected into
hepatocytes to examine the effect of the modifications on targeting of
apoE to intra- and extracellular pools, association of apoE with specific
lipoproteins, and apoE transferability and thrombin sensitivity.
ApoE存在于许多动物物种中,尽管它是
由多种细胞类型合成,大多数血浆apoE由
肝脏 在循环中,apoE通过以下途径参与脂质转运:
介导脂蛋白与B/E受体的结合。 的关键因素
血浆脂质转运是指apoE在血浆中进行脂质交换的能力。
脂蛋白表面;然而,并非所有的apoE都能够转移,
并非所有脂蛋白相关的apoE都是受体活性的。 的因素
其控制脂蛋白和受体结合之间的apoE转移
能力不清楚。 有两条证据表明apoE
由肝脏分泌的脂肪酸可以通过脂肪酸酰化来修饰。 是否
这种酰化与血浆apoE的功能状态无关,
知道的最近有人提出apoE的一部分
由肝细胞合成的蛋白质不被分泌,而是留在细胞内
在那里它可能参与细胞内脂质转运。 信号
它决定了apoE是分泌还是留在细胞内,
然而,在其他系统中,蛋白质靶向特定的
细胞位点通过脂肪酸酰化完成。 的可能性
apoE的脂肪酸酰化可能影响其功能
和/或其在细胞内的运输是有趣的。 的
本项目的目的是了解影响apoE的因素
转移性和受体结合能力以及控制靶向
apoE与细胞内和细胞外池。 这一目标将得以实现
通过四个目的,旨在研究的存在和起源,
探讨apoE的不同物理状态对apoE的影响
功能能力。 第一,身体和生理状态的
将检查新生VLDL(从肝脏分离)的apoE组分
通过测定apoE对凝血酶裂解的敏感性,
apoE转移VLDL的能力,以及apoE转移VLDL的能力。
介导新生VLDL与B/E受体的结合。 第二个目标是
检查apoE的脂肪酸酰化,并确定
在不同的细胞类型和动物物种中apoE酰化,
酰基载脂蛋白E定位于特定脂蛋白类,脂肪酸
酰化的特异性和位点,以及
apoE酰化的后果。 第三个目的是检查细胞
载脂蛋白E酰化的方面,并确定酰化在
apoE靶向细胞内和细胞外池,
载脂蛋白E酰化与蛋白质合成的关系
翻译后修饰和影响apoE的因素
酰化反应。 最后,定点诱变将用于修饰
在apoE的一个或多个酰化位点处,将cDNA转染入
肝细胞,以检查修饰对靶向
apoE与细胞内和细胞外池的关系,apoE与特异性
脂蛋白和apoE转移性和凝血酶敏感性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Martha P. Mims其他文献
Paraneoplastic Nephrotic Syndrome and Inflammatory Arthritis at Diagnosis in Hodgkin Lymphoma
- DOI:
10.1016/j.clml.2012.09.006 - 发表时间:
2013-02-01 - 期刊:
- 影响因子:
- 作者:
Daniel B. Aruch;Martha P. Mims - 通讯作者:
Martha P. Mims
Clinical Outcomes of Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma in a County Hospital System
- DOI:
10.1182/blood-2023-173927 - 发表时间:
2023-11-02 - 期刊:
- 影响因子:
- 作者:
Jun Yang Jiang;Chijioke Nze;Danielle Guffey;Rockbum Kim;Abiodun O. Ouyomi;Omar Rosales;Raka Bandyo;Akiva Diamond;Gustavo A. Rivero;Courtney Nicole Miller-Chism;Mark M. Udden;Martha P. Mims;Christopher R. Flowers;Ang Li;Purnima Sravanti Teegavarapu - 通讯作者:
Purnima Sravanti Teegavarapu
Disparities Among Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia
- DOI:
10.1182/blood-2023-190913 - 发表时间:
2023-11-02 - 期刊:
- 影响因子:
- 作者:
Elyse Lopez;Deepa Dongarwar;Martha P. Mims;Sara Taveras Alam - 通讯作者:
Sara Taveras Alam
Real-World Validation of the European Leukemia Network 2022 Risk Stratification in Acute Myelogenous Leukemia
- DOI:
10.1182/blood-2023-189309 - 发表时间:
2023-11-02 - 期刊:
- 影响因子:
- 作者:
Sarah Elizabeth Mudra;Paul Sackstein;Lacey Scott Williams;Garrett Diltz;Rachel Zemel;Ashwin Kumar;Purnima Sravanti Teegavarapu;Martha P. Mims;Catherine Lai;Kimberley Doucette;Gustavo A. Rivero - 通讯作者:
Gustavo A. Rivero
Clinical outcomes of patients with newly diagnosed large B-cell lymphoma in a safety-net hospital system
- DOI:
10.1016/j.bneo.2024.100020 - 发表时间:
2024-09-01 - 期刊:
- 影响因子:
- 作者:
Jun Y. Jiang;Chijioke Nze;Danielle Guffey;Rockbum Kim;Abiodun O. Oluyomi;Omar Rosales;Raka Bandyo;Courtney N. Miller-Chism;Mark M. Udden;Martha P. Mims;Hilary Ma;Gustavo A. Rivero;Akiva Diamond;Purnima S. Teegavarapu;Ang Li;Christopher R. Flowers - 通讯作者:
Christopher R. Flowers
Martha P. Mims的其他文献
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{{ truncateString('Martha P. Mims', 18)}}的其他基金
DMT1:Tissue specific expression & alternative splicing
DMT1:组织特异性表达
- 批准号:
6858234 - 财政年份:2005
- 资助金额:
$ 16.19万 - 项目类别:
DMT1:Tissue specific expression & alternative splicing
DMT1:组织特异性表达
- 批准号:
7031607 - 财政年份:2005
- 资助金额:
$ 16.19万 - 项目类别:
DYNAMICS OF APOE BINDING TO LIPOPROTEINS AND RECEPTORS
APOE 与脂蛋白和受体结合的动力学
- 批准号:
2223250 - 财政年份:1993
- 资助金额:
$ 16.19万 - 项目类别:
DYNAMICS OF APOE BINDING TO LIPOPROTEINS AND RECEPTORS
APOE 与脂蛋白和受体结合的动力学
- 批准号:
2392677 - 财政年份:1993
- 资助金额:
$ 16.19万 - 项目类别:
DYNAMICS OF APOE BINDING TO LIPOPROTEINS AND RECEPTORS
APOE 与脂蛋白和受体结合的动力学
- 批准号:
2223251 - 财政年份:1993
- 资助金额:
$ 16.19万 - 项目类别:
DYNAMICS OF APOE BINDING TO LIPOPROTEINS AND RECEPTORS
APOE 与脂蛋白和受体结合的动力学
- 批准号:
2223252 - 财政年份:1993
- 资助金额:
$ 16.19万 - 项目类别: