SR-BI MEDIATED SELECTIVE CHOLESTEROL ESTER UPTAKE

SR-BI 介导的选择性胆固醇酯摄取

基本信息

  • 批准号:
    6286827
  • 负责人:
  • 金额:
    $ 22.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-03-01 至 2006-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: There is interest in understanding the factors that regulate HDL and apoA-I levels in humans as these are inversely correlated with the risk for atherosclerotic vascular disease. Plasma levels of HDL and apoA-I are related to the rate of apoA-I catabolism rather than apoA-I production. Neither the mechanisms underlying accelerated catabolism nor the site(s) of apoA-I removal from plasma have been clearly delineated. This proposal focuses on the role of the HDL receptor, SR-B1, in regulating apoA-I catabolic rate. SR-B1 delivers cholesteryl ester to cells via a process that is fundamentally distinct from receptor-mediated endocytosis. During this process, HDL binds to SR-B1 on the cell surface and transfers cholesteryl ester from the core of the particle to the cell without internalization of the apolipoprotein moiety. Despite the absence of apolipoprotein uptake, increased selective lipid uptake in the liver mediated by SR-B1 is associated with increased catabolism of apoA-I, and at least some of this catabolism occurs in the kidney. Thus, a central hypothesis of this proposal is that SR-B1 interaction with HDL initiates changes in the lipoprotein particle that promotes subsequent catabolism by a mechanism that is independent of SR-B1. SR-B1 binds with high affinity a number of different lipoprotein particles in addition to HDL, including VLDL, LDL, and oxidized LDL. The important metabolic event subsequent to lipoprotein binding by SR-B1 is the selective delivery of CE from the core of particles to cells. We propose that apoA-I is a critical ligand for SR-B1-mediated selective uptake, and that apoA-I conformation on the HDL particle can influence its interaction with SR-B1 to impede or promote receptor binding and/or selective uptake. The efficiency of selective uptake mediated by SR-B1:apoA-I interaction can be modulated by properties of the HDL particle (lipid composition, apolipoprotein content, or the structure of apoA-I itself). These hypotheses will be tested by defining: 1) the sub-population of HDL particles that are the preferred substrate for SR-B1-mediated lipid transfer; 2) the structure and composition of HDL particles after processing by SR-B1 (including the potential for apoA-I proteolysis); and 3) the metabolic fate of HDL particles after SR-B1 processing. Understanding the role of SR-B1 in HDL metabolism could define new areas for potential therapeutic assault.
描述:人们对了解调节HDL的因素很感兴趣

项目成果

期刊论文数量(0)
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FREDERICK C. DE BEER其他文献

FREDERICK C. DE BEER的其他文献

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{{ truncateString('FREDERICK C. DE BEER', 18)}}的其他基金

Serum Amyloid A, Inflammasome Activation, and Abdominal Aortic Aneurysms
血清淀粉样蛋白 A、炎症小体激活和腹主动脉瘤
  • 批准号:
    9213910
  • 财政年份:
    2017
  • 资助金额:
    $ 22.05万
  • 项目类别:
HDL Structure and Metabolism During Inflammation
炎症过程中 HDL 的结构和代谢
  • 批准号:
    7219726
  • 财政年份:
    2006
  • 资助金额:
    $ 22.05万
  • 项目类别:
Analytical and Preparative Core
分析和准备核心
  • 批准号:
    7219730
  • 财政年份:
    2006
  • 资助金额:
    $ 22.05万
  • 项目类别:
SR-BI MEDIATED SELECTIVE CHOLESTEROL ESTER UPTAKE
SR-BI 介导的选择性胆固醇酯摄取
  • 批准号:
    6509679
  • 财政年份:
    2001
  • 资助金额:
    $ 22.05万
  • 项目类别:
SAA and sPLA2 Role in Atherogenesis
SAA 和 sPLA2 在动脉粥样硬化形成中的作用
  • 批准号:
    6618079
  • 财政年份:
    2001
  • 资助金额:
    $ 22.05万
  • 项目类别:
SR-BI MEDIATED SELECTIVE CHOLESTEROL ESTER UPTAKE
SR-BI 介导的选择性胆固醇酯摄取
  • 批准号:
    6866412
  • 财政年份:
    2001
  • 资助金额:
    $ 22.05万
  • 项目类别:
SAA and sPLA2 Role in Atherogenesis
SAA 和 sPLA2 在动脉粥样硬化形成中的作用
  • 批准号:
    6442685
  • 财政年份:
    2001
  • 资助金额:
    $ 22.05万
  • 项目类别:
SR-BI MEDIATED SELECTIVE CHOLESTEROL ESTER UPTAKE
SR-BI 介导的选择性胆固醇酯摄取
  • 批准号:
    6707547
  • 财政年份:
    2001
  • 资助金额:
    $ 22.05万
  • 项目类别:
SAA and sPLA2 Role in Atherogenesis
SAA 和 sPLA2 在动脉粥样硬化形成中的作用
  • 批准号:
    6779922
  • 财政年份:
    2001
  • 资助金额:
    $ 22.05万
  • 项目类别:
SR-BI MEDIATED SELECTIVE CHOLESTEROL ESTER UPTAKE
SR-BI 介导的选择性胆固醇酯摄取
  • 批准号:
    6629853
  • 财政年份:
    2001
  • 资助金额:
    $ 22.05万
  • 项目类别:

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Cholesterol esters of oligodendrocytes in developmental and ageing brain
发育和衰老大脑中少突胶质细胞的胆固醇酯
  • 批准号:
    BB/S000844/1
  • 财政年份:
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Cholesterol Esters in Hormone Production By Steroidogenic Tissues
类固醇生成组织产生激素中的胆固醇酯
  • 批准号:
    7715237
  • 财政年份:
    1977
  • 资助金额:
    $ 22.05万
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    Standard Grant
A DIRECT FLUOROMETRIC DETERMINATION OF SERUM CHOLESTEROL ESTERS
直接荧光法测定血清胆固醇酯
  • 批准号:
    3914069
  • 财政年份:
  • 资助金额:
    $ 22.05万
  • 项目类别:
A DIRECT FLUORMETRIC DETERMINATION OF SERUM CHOLESTEROL ESTERS
直接荧光法测定血清胆固醇酯
  • 批准号:
    3894769
  • 财政年份:
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