The Role of ABCA1 in HDL Subfraction Formation
The Role of ABCA1 in HDL Subfraction Formation
批准号:
7450736
负责人:
JOHN E PARKS
金额:
$35.56万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
ATP-Binding Cassette TransportersAgonistAlbuminsAnimalsApolipoprotein A-IApolipoprotein A-IIApolipoproteinsApolipoproteins ABiliaryCatabolismCell LineCellobioseCellsChargeCholesterolComplementary DNAConfounding Factors (Epidemiology)Coronary heart diseaseCulture MediaCultured CellsDataDevelopmentDietEthersEthyl EtherEventExcretory functionGelGene TargetingGenerationsGoalsGrantHepaticHepatocyteHeterogeneityHigh Density LipoproteinsHumanIn VitroIntestinesKnockout MiceKnowledgeLeadLipidsLipoprotein (a)Lipoprotein (a-)LipoproteinsLiverMeasuresMembrane Transport ProteinsMetabolicMetabolic Clearance RateMetabolic PathwayMetabolismMethodsMiningMolecularMolecular Sieve ChromatographyMonitorMusParticle SizePathway interactionsPeripheralPhospholipidsPlasmaPopulation HeterogeneityPositioning AttributeProcessProductionRadiolabeledRateRiskRoleSepharoseSiteTestingTimeTissuesTransfectionTransgenic MiceTransgenic OrganismsTyramineUp-RegulationWild Type Mousebasedenaturing gradient gel electrophoresisdensitymacrophagenonhuman primatenovelparticlepre-beta high-density lipoproteinprotective effectradiotracerreceptorresidencereverse cholesterol transportsaturated fatsizeuptake
中文摘要
高密度脂蛋白(hdl)的浓度与糖尿病风险呈负相关
英文摘要
The concentration of high density lipoproteins (HDLs) is inversely associated with the risk of devel-
oping premature coronary heart disease, but our understanding of the metabolic pathways that con-
trol plasma HDL concentrations is limited. HDLs exist in plasma as discrete size subfractions that
can be separated by apolipoprotein content and size into small, medium, and large particles con-
taining two, three, and four molecules of apolipoprotein A-I (apoA-l) per particle. The overall goal of
this project is to elucidate the molecular pathways of HDL subfraction formation to fill the gaps in
knowledge of factors that control plasma concentrations of HDL and HDL subfraction heterogeneity.
Our previous studies and preliminary data have described a novel pathway for HDL subfraction me-
tabolism in non-human primates and in human apoA-I transgenic mice in which small HDL are con-
verted in a unidirectional pathway to medium or large HDL before being removed from plasma and
catabolized by the liver. Furthermore, our data show no evidence for the production of pre-beta
apoA-I during the catabolism of large HDL. In the next grant cycle, we propose to investigate the
molecular pathways of HDL subfraction metabolism using transgenic and gene targeted mice to
elucidate the molecular details of HDL subfraction particle assembly, intravascular metabolism, and
tissue catabolism. In Specific aim 1, we will test the hypothesis that the liver and intestine are the
major sites of nascent HDL assembly using hepatic and intestinal specific AbcA1 transporter
knockout mice. In Specific aim 2, we will test the hypothesis that hepatic AbcA1 function is rate
limiting in the assembly of lipid free apoA-I with lipid to form small nascent discoidal HDL particles.
In Specific aim 3, we will test the hypothesis that AbcA1 is involved in the addition of lipid to small
spherical plasma HDL and their subsequent conversion to medium and large HDL particles outside
the plasma compartment. The results of these proposed studies will increase our basic under-
standing of the role of AbcAl in the formation and maturation of HDL subfractions and may lead to
a better understanding of ways to increase plasma HDL concentrations or stimulate reverse choles-
terol transport by dietary or pharmacological methods.
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The Role of ABCA1 in HDL Subfraction Formation
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批准号:7000691
-
项目类别:
-
资助金额:$31.73万
-
财政年份:2004
-
负责人:JOHN E PARKS
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依托单位:
PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES
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批准号:6345242
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项目类别:
-
资助金额:$0.62万
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财政年份:2000
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负责人:JOHN E PARKS
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依托单位:
PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES
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批准号:6478966
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项目类别:
-
资助金额:$5.36万
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财政年份:2000
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负责人:JOHN E PARKS
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依托单位:
PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES
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批准号:6206437
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项目类别:
-
资助金额:$0.62万
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财政年份:1999
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负责人:JOHN E PARKS
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依托单位:
PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES
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批准号:6123277
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项目类别:
-
资助金额:$0.0万
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财政年份:1998
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负责人:JOHN E PARKS
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依托单位:
PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES
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批准号:6254164
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项目类别:
-
资助金额:$1.96万
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财政年份:1997
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负责人:JOHN E PARKS
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依托单位:
SPERM MEMBRANE LIPID CHANGES RELATED TO FERTILIZATION
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批准号:3447986
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项目类别:
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资助金额:$5.53万
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财政年份:1984
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负责人:JOHN E PARKS
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依托单位:
SPERM MEMBRANE LIPID CHANGES RELATED TO FERTILIZATION
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批准号:3447987
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项目类别:
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资助金额:$5.14万
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财政年份:1984
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负责人:JOHN E PARKS
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依托单位:
The Role of ABCA1 in HDL Subfraction Formation
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批准号:7440945
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项目类别:
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资助金额:$33.67万
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财政年份:--
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负责人:JOHN E PARKS
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依托单位:
The Role of ABCA1 in HDL Subfraction Formation
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批准号:7440939
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项目类别:
-
资助金额:$32.69万
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财政年份:--
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负责人:JOHN E PARKS
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依托单位:
国内基金
海外基金
Agonist-GPR119-Gs复合物的结构生物学研究
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批准号:32000851
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项目类别:青年科学基金项目
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资助金额:24.0万元
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批准年份:2020
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负责人:乔安娜
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依托单位: