Apoptotic Signaling Induces Hyperpermeability Following Hemorrhagic Shock
凋亡信号传导导致失血性休克后通透性过高
基本信息
- 批准号:7616069
- 负责人:
- 金额:$ 13.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-09-25 至 2011-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdherenceAdherens JunctionAdhesivesAgeAmerican Heart AssociationAnimal ModelApoptosisApoptoticAreaAtomic Force MicroscopyAttenuatedAwardBasement membraneBiologyBlood CirculationBlood VesselsBurn TraumaCardiogenic ShockCardiovascular PhysiologyCardiovascular systemCaspaseCause of DeathCell CommunicationCell DeathCellsCellular biologyCessation of lifeCleaved cellClinicalComplementComplexDataDevelopmentDrug Delivery SystemsEdemaEndothelial CellsEnvironmentFaceFunctional disorderFundingGoalsGrantHandHemorrhagic ShockHomeostasisInjuryInstitutionInterdisciplinary StudyInterventionInvestigationIschemiaJournalsLaboratoriesLiquid substanceLungMediator of activation proteinMentored Research Scientist Development AwardMitochondriaModelingModificationMolecular BiologyNervous system structureNeurologyOrganPathway interactionsPermeabilityProteinsRegulationResearchResearch DesignResearch PersonnelSepsisShockSignal TransductionSiteStimulusStructureTechniquesTestingTherapeuticTissuesTransfectionTraumaUnited States National Institutes of HealthVascular PermeabilitiesWorkabstractingbasecadherin 5caspase-3designexperiencein vivoinnovationinsightinterstitialintravital microscopymonolayernovelpressurepreventprogramsresearch studyskillsstatisticssymposiumtreatment strategy
项目摘要
DESCRIPTION (provided by applicant):
This application describes a comprehensive vascular research program designed to develop Dr. Childs into an independent investigator. Through course work in molecular biology, research design, and statistics, he will acquire the necessary analytical skills to achieve this goal. He will also be required to attend several annual conferences and a monthly journal club. An Advisory Board of experienced investigators in vascular and cellular biology has been established for Dr. Childs to obtain hands on experience in laboratory techniques. Development of grantsmanship is emphasized throughout the duration of the K01 award, beginning with applications for local funds, graduating to an American Heart Association grant, and culminating in a R01 submission to the NIH in the third year of this award. The research plan focuses on the regulation of endothelial cell-cell adherens junctions to prevent microvascular hyperpermeability following hemorrhagic shock. Fluid loss from the circulation is a major factor in compromising cardiovascular homeostasis following trauma, burns, sepsis and hemorrhagic shock. Preventing microvascular barrier opening or reestablishing barrier function is crucial in limiting the deleterious effects on the cardiovascular, pulmonary and nervous systems. Hemorrhagic shock-induced hyperpermeability results in alteration of the endothelial cell-cell adherens junction complex. Site-specific alterations in the structure of (3-catenin have been implicated as an important modulator of these junctions. The applicant hypothesizes that hemorrhagic shock-induced activation of caspases results in a (3- catenin-dependent modification of endothelial adherens junction. To address this hypothesis, the applicant proposes two interlocking specific aims: (1) define the relationship between the apoptotic cascade and hemorrhagic shock-induced hyperpermeability and (2) identify the interaction(s) of caspase-3 with the adherens junction complex. Intravital microscopy with a novel in vivo protein transfection technique in parallel with cell monolayers will be utilized to determine changes in microvascular hyperpermeability. Atomic force microscopy will be used to assess endothelial cell adhesive forces. (End of Abstract)
描述(由申请人提供):
本申请描述了一个全面的血管研究计划,旨在发展博士查尔兹成为一个独立的调查。通过分子生物学,研究设计和统计学课程,他将获得必要的分析技能,以实现这一目标。他还将被要求参加几个年度会议和一个月刊俱乐部。为查尔兹博士建立了一个由血管和细胞生物学方面经验丰富的研究人员组成的咨询委员会,以获得实验室技术方面的实践经验。在整个K 01奖项期间,都强调了granulocytosis的发展,从申请当地基金开始,毕业到美国心脏协会拨款,并在该奖项的第三年向NIH提交R 01申请。该研究计划的重点是调节内皮细胞-细胞粘附连接,以防止失血性休克后微血管通透性过高。循环中的液体流失是创伤、烧伤、脓毒症和失血性休克后损害心血管稳态的主要因素。防止微血管屏障开放或重建屏障功能对于限制对心血管、肺和神经系统的有害影响至关重要。失血性休克诱导的高通透性导致内皮细胞-细胞粘附连接复合物的改变。β-连环蛋白结构的位点特异性改变被认为是这些连接的重要调节剂。申请人假设失血性休克诱导的半胱天冬酶激活导致内皮粘附连接的β-连环蛋白依赖性修饰。为了解决这一假设,申请人提出了两个互锁的具体目标:(1)定义凋亡级联与出血性休克诱导的高通透性之间的关系,以及(2)鉴定半胱天冬酶-3与粘附连接复合物的相互作用。将利用与细胞单层平行的新型体内蛋白质转染技术的活体显微镜来确定微血管通透性过高的变化。将使用原子力显微镜评估内皮细胞粘附力。(End摘要)
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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{{ truncateString('ED W CHILDS', 18)}}的其他基金
Apoptotic Signaling Induces Hyperpermeability Following Hemorrhagic Shock
凋亡信号传导导致失血性休克后通透性过高
- 批准号:
7291594 - 财政年份:2006
- 资助金额:
$ 13.61万 - 项目类别:
Apoptotic Signaling Induces Hyperpermeability Following Hemorrhagic Shock
凋亡信号传导导致失血性休克后通透性过高
- 批准号:
7417435 - 财政年份:2006
- 资助金额:
$ 13.61万 - 项目类别:
Apoptotic Signaling Induces Hyperpermeability Following
细胞凋亡信号传导导致通透性过高
- 批准号:
7100474 - 财政年份:2006
- 资助金额:
$ 13.61万 - 项目类别:
Apoptotic Signaling Induces Hyperpermeability Following Hemorrhagic Shock
凋亡信号传导导致失血性休克后通透性过高
- 批准号:
7806477 - 财政年份:2006
- 资助金额:
$ 13.61万 - 项目类别:
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