Role of Adenosine Receptors in Tissue Protection
腺苷受体在组织保护中的作用
基本信息
- 批准号:7212061
- 负责人:
- 金额:$ 35.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-04-18 至 2010-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdenosineAdenosine A3 ReceptorAgonistAnti-Inflammatory AgentsAnti-inflammatoryArtsBone MarrowCanis familiarisCardiacCardiac MyocytesCellsClinicalDiseaseEndothelial CellsGenesGeneticGoalsHeartImmuneInfarctionInflammationInflammatoryInflammatory ResponseInjuryIschemiaKnock-outKnockout MiceMediatingModelingMusMyocardialMyocardial IschemiaMyocardiumOryctolagus cuniculusPathogenesisPhysiological reperfusionPopulationPurinergic P1 ReceptorsReceptor GeneRelative (related person)Reperfusion InjuryReperfusion TherapyResearch ProposalsRoleSignal TransductionStandards of Weights and MeasuresStressTechniquesTimeTissuesTransplantationadenosine receptor activationautocrinechemokinecongeniccytokinein vivomacrophagemouse modelneutrophilparacrinereceptorresponse
项目摘要
DESCRIPTION (provided by applicant): Current evidence suggests that A3 adenosine receptors (A3ARs) are expressed in cardiac myocytes, where they regulate responses to ischemic stress. In addition, A3ARs are expressed in cells involved in the inflammatory response including neutrophils, macrophages, and endothelial cells. In these cells, they mediate anti-inflammatory actions. In preliminary studies, we have shown that newly developed A3AR agonists provide profound cardiac protection against tissue damage induced by myocardial ischemia/reperfusion (I/R) injury in mice, rabbits, and dogs whether they are given prior to ischemia or at the time of reperfusion. The goal of this research proposal is to understand the mechanisms responsible for this tissue protection. Our general hypothesis is that A3AR agonists act dually on cardiac myocytes to reduce myocardial injury during ischemia, and act on bone marrow-derived cells to reduce inflammation during reperfusion. The studies involve the use of genetic approaches to: 1) produce a congenic line of mice with the A3AR gene selectively deleted from cardiomyocytes using the Cre/LoxP strategy, and 2) to produce from congenic A3AR gene "knock-out" mice, chimeric mice lacking or expressing the A3AR in bone marrow-derived cells using standard transplantation techniques. An in vivo mouse model of infarction and an isolated mouse heart model of global ischemia and reperfusion will be used to determine the relative importance of A3ARs expressed in the myocardium versus inflammatory cells in regulating I/R injury. Additional studies are proposed to study cellular signaling responses of A3ARs in specific populations of inflammatory cells from "wild-type", conventional A2AAR gene "knock-out", and conventional A3AR gene knock-out" mice. Collectively, these studies will combine several state-of-the-art techniques to provide new definitive information on the cell-specific mechanisms by which A3AR activation provides protection from I/R injury.
描述(由申请人提供):目前的证据表明,A3腺苷受体(A3ARs)在心肌细胞中表达,在心肌细胞中调节对缺血应激的反应。此外,A3ARs在参与炎症反应的细胞中表达,包括中性粒细胞、巨噬细胞和内皮细胞。在这些细胞中,它们介导抗炎作用。在初步研究中,我们已经表明,新开发的A3AR激动剂对小鼠、兔子和狗心肌缺血/再灌注(I/R)损伤引起的组织损伤具有深远的心脏保护作用,无论是在缺血前还是在再灌注时给予。这项研究计划的目标是了解负责这种组织保护的机制。我们的一般假设是A3AR激动剂双重作用于心肌细胞以减轻缺血时的心肌损伤,并作用于骨髓源性细胞以减少再灌注时的炎症。这些研究涉及使用遗传方法:1)使用Cre/LoxP策略从心肌细胞中选择性地删除A3AR基因,产生同源小鼠系;2)使用标准移植技术从同源A3AR基因“敲除”小鼠中产生缺乏或在骨髓来源细胞中表达A3AR的嵌合小鼠。我们将使用小鼠梗死的体内模型和小鼠心肌缺血再灌注的离体模型来确定心肌中表达的A3ARs与炎症细胞在调节I/R损伤中的相对重要性。进一步研究A3ARs在“野生型”、常规A2AAR基因“敲除”和常规A3AR基因“敲除”小鼠的特定炎症细胞群中的细胞信号反应。总的来说,这些研究将结合几种最先进的技术,以提供关于A3AR激活对I/R损伤提供保护的细胞特异性机制的新的明确信息。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JOHN A AUCHAMPACH其他文献
JOHN A AUCHAMPACH的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JOHN A AUCHAMPACH', 18)}}的其他基金
Adenosine Signaling During Post-Infarction Remodeling and Heart Failure
梗死后重塑和心力衰竭期间的腺苷信号转导
- 批准号:
9317191 - 财政年份:2017
- 资助金额:
$ 35.91万 - 项目类别:
EET-Induced Cardioprotection: Role of Opioids and Nitric Oxide (NO)
EET 诱导的心脏保护作用:阿片类药物和一氧化氮 (NO) 的作用
- 批准号:
8431782 - 财政年份:2012
- 资助金额:
$ 35.91万 - 项目类别:
EET-Induced Cardioprotection: Role of Opioids and Nitric Oxide (NO)
EET 诱导的心脏保护作用:阿片类药物和一氧化氮 (NO) 的作用
- 批准号:
8608431 - 财政年份:2012
- 资助金额:
$ 35.91万 - 项目类别:
Role of Adenosine Receptors in Tissue Protection
腺苷受体在组织保护中的作用
- 批准号:
7388215 - 财政年份:2005
- 资助金额:
$ 35.91万 - 项目类别:
Role of Adenosine Receptors in Tissue Protection
腺苷受体在组织保护中的作用
- 批准号:
7055253 - 财政年份:2005
- 资助金额:
$ 35.91万 - 项目类别:
Role of Adenosine Receptors in Tissue Protection
腺苷受体在组织保护中的作用
- 批准号:
8040564 - 财政年份:2005
- 资助金额:
$ 35.91万 - 项目类别:
Role of Adenosine Receptors in Tissue Protection
腺苷受体在组织保护中的作用
- 批准号:
8387001 - 财政年份:2005
- 资助金额:
$ 35.91万 - 项目类别:
Role of Adenosine Receptors in Tissue Protection
腺苷受体在组织保护中的作用
- 批准号:
7587248 - 财政年份:2005
- 资助金额:
$ 35.91万 - 项目类别:
Role of Adenosine Receptors in Tissue Protection
腺苷受体在组织保护中的作用
- 批准号:
8588955 - 财政年份:2005
- 资助金额:
$ 35.91万 - 项目类别:
相似海外基金
The Biology of Microglia: Adenosine A3 Receptor Suppression
小胶质细胞的生物学:腺苷 A3 受体抑制
- 批准号:
RGPIN-2019-06289 - 财政年份:2022
- 资助金额:
$ 35.91万 - 项目类别:
Discovery Grants Program - Individual
The Biology of Microglia: Adenosine A3 Receptor Suppression
小胶质细胞的生物学:腺苷 A3 受体抑制
- 批准号:
RGPIN-2019-06289 - 财政年份:2021
- 资助金额:
$ 35.91万 - 项目类别:
Discovery Grants Program - Individual
Molecular basis for adenosine A3 receptor agonists in the treatment of migraine
腺苷A3受体激动剂治疗偏头痛的分子基础
- 批准号:
10532300 - 财政年份:2021
- 资助金额:
$ 35.91万 - 项目类别:
Molecular basis for adenosine A3 receptor agonists in the treatment of migraine
腺苷A3受体激动剂治疗偏头痛的分子基础
- 批准号:
10363152 - 财政年份:2021
- 资助金额:
$ 35.91万 - 项目类别:
The Biology of Microglia: Adenosine A3 Receptor Suppression
小胶质细胞的生物学:腺苷 A3 受体抑制
- 批准号:
RGPIN-2019-06289 - 财政年份:2020
- 资助金额:
$ 35.91万 - 项目类别:
Discovery Grants Program - Individual
The Biology of Microglia: Adenosine A3 Receptor Suppression
小胶质细胞的生物学:腺苷 A3 受体抑制
- 批准号:
RGPIN-2019-06289 - 财政年份:2019
- 资助金额:
$ 35.91万 - 项目类别:
Discovery Grants Program - Individual
Use of fluorescence correlation spectroscopy to study the adenosine A3-receptor in microdomains of single living cells
使用荧光相关光谱研究单个活细胞微区中的腺苷 A3 受体
- 批准号:
G0800006/1 - 财政年份:2009
- 资助金额:
$ 35.91万 - 项目类别:
Research Grant
Role of adenosine A3 receptor in suppressing prostate cancer
腺苷A3受体在抑制前列腺癌中的作用
- 批准号:
7516278 - 财政年份:2008
- 资助金额:
$ 35.91万 - 项目类别: