Massive Cardiac Endocytosis and Ectosome Shedding
Massive Cardiac Endocytosis and Ectosome Shedding
批准号:
9766352
负责人:
DONALD W HILGEMANN
金额:
$37.59万
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-04-01 至 2022-04-30
关键词:
Acyl Coenzyme AAcylationAcyltransferaseAffectAnoxiaCardiacCardiac MyocytesCarnitineCaspaseCause of DeathCellsCessation of lifeChronicChronic DiseaseClinicalCoenzyme ACoupledCytoskeletonDegenerative DisorderDevelopmentDiagnosisDiseaseDrug TargetingEndocytosisEndocytosis PathwayEnzymesEventExtracellular SpaceG2A receptorGenerationsGlyburideHeartHepatitisIndividualInterventionJUN geneLifeLinkLipidsLymphocyteLysophosphatidylcholinesMalignant NeoplasmsMediatingMembraneMembrane ProteinsMetabolic stressMitochondriaMolecularMusMuscle CellsNADPH OxidaseNeurodegenerative DisordersNonesterified Fatty AcidsNucleotidesOxidative StressPathologicPathway interactionsPeptidesPermeabilityPharmaceutical PreparationsPhasePhospholipase A2PhospholipidsPhysiologicalPhysiologyPlayProcessProteinsPublic HealthReactionReactive Oxygen SpeciesReperfusion InjuryRoleSarcolemmaSecond Messenger SystemsSepsisSignal PathwaySignal TransductionSurfaceTestingVariantWorkacylcarnitinedrug discoveryfatty acid metabolismheart functioninhibitor/antagonistinsightlipid metabolismmitochondrial dysfunctionmitochondrial metabolismmitochondrial permeability transition poremonolayernovel therapeuticsoxidationpalmitoylationplatelet activating factor receptorpreventprotein aggregateprotein protein interactionreceptortooltrait
中文摘要
摘要
该项目的重点是心脏信号通路,其中脂质代谢,再加上
线粒体活性状态,通过内吞作用促进大量肌膜内化
在一些实施方案中,细胞外体脱落(MEND)和/或大量外体脱落(MESS)至细胞外间隙。的
内吞途径取决于脂肪酸代谢和生成
胞质酰基辅酶A,用于使许多肌膜蛋白质脂质化。
脱落途径主要取决于溶血磷脂酰胆碱的产生,
其受体在心肌细胞中的激活,以及随后的
单层之间的肌膜磷脂。这两种机制似乎都依赖于
对肌膜内有序膜结构域的产生有影响,
促进独特的蛋白质-蛋白质相互作用和功能。这两种机制都是
预期在发生在细胞膜重塑中起主要作用,
缺血/再灌注损伤,以及主要的慢性退行性疾病,
氧化应激使用多个在这些途径中存在缺陷的小鼠品系,以及
药物来操纵个体反应,我们将分析其共性,
这些途径的独特特征,确定必要的分子球员,因素,
决定性地将肌膜推到MEND或MESS,并更精确地定义
MEND和MESS的生理和病理作用。该项目将提供洞察力
基本的细胞调节机制,对一个
了解发达国家的主要死亡原因。
英文摘要
ABSTRACT
This project focuses on cardiac signaling pathways in which lipid metabolism, coupled to
mitochondrial activity state, promote massive sarcolemma internalization via endocytosis
(MEND) and/or massive ectosome shedding (MESS) to the extracellular space. The
endocytosis pathway depends on fatty acid metabolism and the generation of
cytoplasmic acyl-coenzyme A that is used to lipidate numerous sarcolemmmal proteins.
The shedding pathway depends primarily on the generation of lysophosphatidylcholine,
the activation of its receptors in the cardiac myocyte, and subsequent scrambling of
sarcolemmal phospholipids between monolayers. Both mechanisms appear to depend
on the generation of ordered membrane domains within the sarcolemma which then
facilitate unique protein-protein interactions and functions. Both mechanisms are
expected to play major roles in membrane remodeling that occurs in
ischemia/reperfusion injury, as well as in major chronic, degenerative diseases involving
oxidative stress. Using multiple mice lines with deficiencies in these pathways, as well as
drugs to manipulate individual reactions, we will analyze the commonalities and
distinctive traits of these pathways, identify the essential molecular players, factors that
decisively push the sarcolemma to MEND or MESS, and define more precisely the
physiological and pathological roles of MEND and MESS. The project will provide insight
into fundamental cell regulatory mechanisms that have a high impact for an
understanding of the leading causes of death in the developed world.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Palmitoylation-dependent massive endocytosis (pMEND)
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批准号:9043177
-
项目类别:
-
资助金额:$39.75万
-
财政年份:2014
-
负责人:DONALD W HILGEMANN
-
依托单位:
Palmitoylation-dependent massive endocytosis (pMEND)
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批准号:8698126
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项目类别:
-
资助金额:$39.75万
-
财政年份:2014
-
负责人:DONALD W HILGEMANN
-
依托单位:
Massive Cardiac Endocytosis and Ectosome Shedding
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批准号:9920758
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项目类别:
-
资助金额:$40.5万
-
财政年份:2014
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负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac function and PIP2
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批准号:7150002
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项目类别:
-
资助金额:$36.98万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac Function and PIP2
-
批准号:7799231
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项目类别:
-
资助金额:$38.11万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac function and PIP2
-
批准号:6828274
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项目类别:
-
资助金额:$39.0万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac function and PIP2
-
批准号:6587052
-
项目类别:
-
资助金额:$39.0万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac Function and PIP2
-
批准号:8242761
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项目类别:
-
资助金额:$37.73万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac function and PIP2
-
批准号:6696607
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项目类别:
-
资助金额:$39.0万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac Function and PIP2
-
批准号:8039956
-
项目类别:
-
资助金额:$38.11万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac Function and PIP2
-
批准号:8442883
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项目类别:
-
资助金额:$35.92万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac Function and PIP2
-
批准号:7653258
-
项目类别:
-
资助金额:$35.26万
-
财政年份:2003
-
负责人:DONALD W HILGEMANN
-
依托单位:
Cardiac function and PIP2
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批准号:6990543
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项目类别:
-
资助金额:$38.08万
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财政年份:2003
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负责人:DONALD W HILGEMANN
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依托单位:
Mechanisms of Membrane Transport Gordon Conference
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批准号:6348728
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项目类别:
-
资助金额:$1.91万
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财政年份:2001
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负责人:DONALD W HILGEMANN
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依托单位:
THIRD INTERNATIONAL CONFERENCE ON NA+/CA++ EXCHANGE
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批准号:2231756
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项目类别:
-
资助金额:$1.0万
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财政年份:1995
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负责人:DONALD W HILGEMANN
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依托单位:
FUNCTION AND REGULATION OF NA/CA EXCHANGERS
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批准号:2766214
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项目类别:
-
资助金额:$34.47万
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财政年份:1994
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负责人:DONALD W HILGEMANN
-
依托单位:
FUNCTION AND REGULATION OF NA/CA EXCHANGERS
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批准号:6343531
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项目类别:
-
资助金额:$29.21万
-
财政年份:1994
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负责人:DONALD W HILGEMANN
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依托单位:
FUNCTION AND REGULATION OF NA/CA EXCHANGERS
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批准号:6139172
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项目类别:
-
资助金额:$28.9万
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财政年份:1994
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负责人:DONALD W HILGEMANN
-
依托单位:
FUNCTION AND REGULATION OF NA/CA EXCHANGERS
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批准号:6490552
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项目类别:
-
资助金额:$30.25万
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财政年份:1994
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负责人:DONALD W HILGEMANN
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依托单位:
FUNCTION AND REGULATION OF NA/CA EXCHANGERS
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批准号:6627449
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项目类别:
-
资助金额:$29.71万
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财政年份:1994
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负责人:DONALD W HILGEMANN
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依托单位:
海外基金