Homeostatic Roles of Connexin43 in Response to DNA Damage
Connexin43 在 DNA 损伤反应中的稳态作用
基本信息
- 批准号:7805954
- 负责人:
- 金额:$ 4.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-03-01 至 2015-02-28
- 项目状态:已结题
- 来源:
- 关键词:AffectAgeAgingAging-Related ProcessAntibodiesApoptosisBiological AssayCSNK1A1 geneCell CommunicationCell ProliferationCell SurvivalCell physiologyCellsCessation of lifeConnexin 43ConnexinsCorneaCorneal EndotheliumDNA DamageDNA RepairDataDetergentsDeteriorationEndothelial CellsEpitheliumEventExposure toFutureGap JunctionsGenesGenotoxic StressGoalsHomeostasisIn VitroIntercellular Communication InhibitionLeadLinkMaintenanceMediatingModificationMolecularMusOrganPermeabilityPhosphorylationPhosphotransferasesPhysiologicalProteinsPumpRNA InterferenceResistanceRoleSignal TransductionSiteStressTestingTissuesage relatedanterior chamberbiological adaptation to stresscasein kinasecasein kinase Icell injurycopingcoping mechanismdriving forcein vitro Modelin vivoinhibitor/antagonistinsightintercellular communicationlensneuronal cell bodyresponsestressortrafficking
项目摘要
DESCRIPTION (provided by applicant): DNA damage can significantly alter cell function and viability, thus, the accumulation of unrepaired DNA damage is believed to be a major influence in the deterioration of organ function in aging. However, cells also respond to DNA damage in many other ways beyond DNA repair in order to maintain their function and viability. In particular, genes involved in intercellular communication, such as connexins, have been identified as key components in cellular responses to numerous stressors. Despite this, the molecular mechanisms by which intercellular communication is modified after genotoxic stress have not been described. The overall goal of this F30 proposal is to understand the responses to DNA damage in corneal endothelial (CE) cells whose pump and barrier functions are essential for corneal transparency and which in vivo display age-related degeneration and accumulation of DNA damage. Using an in vitro model of CE cells, we have recently observed significant changes in the gap junction protein connexin-43 (Cx43) after exposure to DNA damage-inducing agents. To explain the cellular mechanism(s) behind these changes, we consider a potential link between DNA damage and cell communication via casein kinase-1 delta (CK1?), which is both activated by DNA damage and an essential Cx43 kinase. Our overall hypothesis is that a protective cellular response to DNA damage involves stabilization of gap junction intercellular communication which is (a) mediated by changes in Cx43 expression and site-specific phosphorylation by CK1?), and (b) required for maintenance of viability and function. This will be tested with two specific aims that will determine 1) the mechanism(s) by which DNA damage mediates modification of connexin-43 (Cx43) and 2) the physiological consequence(s) of these changes during DNA damage including effects of CE cell viability and function. The results of this project will further our understanding of stress responses to DNA damage and provide insights into how the viability of certain aging tissues may be potentially enhanced. The aging process in which the body's cells, tissues, and organs progressively deteriorate has been associated with the accumulation of DNA damage. In response to such stress, a cell may survive or perish depending on its ability to cope with that damage. This proposal studies a potential coping mechanism to DNA damage that involves changes in how damaged cells communicate with one another to maintain their function and viability.
描述(申请人提供):DNA损伤可以显著改变细胞的功能和活力,因此,未修复的DNA损伤的积累被认为是衰老过程中器官功能恶化的主要影响因素。然而,细胞也以DNA修复以外的许多其他方式对DNA损伤做出反应,以维持其功能和生存能力。尤其是参与细胞间通讯的基因,如连接蛋白,已被确定为细胞对多种应激源做出反应的关键组成部分。尽管如此,遗传毒性应激后细胞间通讯被改变的分子机制还没有被描述。这个F30提案的总体目标是了解角膜内皮细胞对DNA损伤的反应,这些细胞的泵和屏障功能对于角膜透明是必不可少的,并且在体内表现出与年龄相关的DNA损伤的退化和积累。利用CE细胞的体外模型,我们最近观察到DNA损伤诱导剂暴露后缝隙连接蛋白Cx43(Cx43)的显著变化。为了解释这些变化背后的细胞机制(S),我们认为DNA损伤和通过酪蛋白激酶-1增量(CK1?)进行的细胞通讯之间存在潜在的联系,CK1?既被DNA损伤激活,也是一种必不可少的Cx43激酶。我们的总体假设是,细胞对DNA损伤的保护性反应包括稳定缝隙连接的细胞间通讯,这种通讯是(A)通过Cx43表达的变化和CK1?的位点特异性磷酸化来调节的,以及(B)维持生存和功能所必需的。这将通过两个特定的目的进行测试,以确定1)DNA损伤介导连接蛋白43(Cx43)修饰的机制(S)和2)DNA损伤过程中这些变化的生理后果(S),包括对CE细胞存活和功能的影响。该项目的结果将进一步加深我们对DNA损伤的应激反应的理解,并为如何潜在地增强某些老化组织的生存能力提供见解。人体细胞、组织和器官逐渐退化的衰老过程与DNA损伤的积累有关。作为对这种压力的反应,细胞的存活或死亡取决于其应对这种损伤的能力。这项建议研究了一种潜在的应对DNA损伤的机制,涉及改变受损细胞相互沟通的方式,以维持其功能和生存能力。
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 }}
Daniel Sam Roh其他文献
Daniel Sam Roh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('Daniel Sam Roh', 18)}}的其他基金
Targeting Senescence to Improve Wound Healing in Aging
靶向衰老以改善衰老过程中的伤口愈合
- 批准号:
10729963 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Role of Senescence in the Impaired Wound Healing of Aging
衰老在衰老伤口愈合受损中的作用
- 批准号:
10027701 - 财政年份:2020
- 资助金额:
$ 4.62万 - 项目类别:
Role of Senescence in the Impaired Wound Healing of Aging
衰老在衰老伤口愈合受损中的作用
- 批准号:
10251307 - 财政年份:2020
- 资助金额:
$ 4.62万 - 项目类别:
Homeostatic Roles of Connexin43 in Response to DNA Damage
Connexin43 在 DNA 损伤反应中的稳态作用
- 批准号:
8215633 - 财政年份:2010
- 资助金额:
$ 4.62万 - 项目类别:
Homeostatic Roles of Connexin43 in Response to DNA Damage
Connexin43 在 DNA 损伤反应中的稳态作用
- 批准号:
8044043 - 财政年份:2010
- 资助金额:
$ 4.62万 - 项目类别:
Homeostatic Roles of Connexin43 in Response to DNA Damage
Connexin43 在 DNA 损伤反应中的稳态作用
- 批准号:
8403696 - 财政年份:2010
- 资助金额:
$ 4.62万 - 项目类别:
相似国自然基金
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
- 批准号:JCZRQN202500010
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
- 批准号:2025JJ70209
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
- 批准号:
- 批准年份:2024
- 资助金额:0 万元
- 项目类别:面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
- 批准号:2023JJ50274
- 批准年份:2023
- 资助金额:0.0 万元
- 项目类别:省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
- 批准号:81602908
- 批准年份:2016
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
- 批准号:81501928
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
相似海外基金
The Phenomenon of Stem Cell Aging according to Methylation Estimates of Age After Hematopoietic Stem Cell Transplantation
根据造血干细胞移植后甲基化年龄估算干细胞衰老现象
- 批准号:
23K07844 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of Age-dependent Functional Changes in Skeletal Muscle CB1 Receptors by an in Vitro Model of Aging-related Muscle Atrophy
通过衰老相关性肌肉萎缩的体外模型分析骨骼肌 CB1 受体的年龄依赖性功能变化
- 批准号:
22KJ2960 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Joint U.S.-Japan Measures for Aging and Dementia Derived from the Prevention of Age-Related and Noise-induced Hearing Loss
美日针对预防与年龄相关和噪声引起的听力损失而导致的老龄化和痴呆症联合措施
- 批准号:
23KK0156 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Fund for the Promotion of Joint International Research (International Collaborative Research)
The Effects of Muscle Fatigability on Gait Instability in Aging and Age-Related Falls Risk
肌肉疲劳对衰老步态不稳定性和年龄相关跌倒风险的影响
- 批准号:
10677409 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Characterizing gut physiology by age, frailty, and sex: assessing the role of the aging gut in "inflamm-aging"
按年龄、虚弱和性别表征肠道生理学特征:评估衰老肠道在“炎症衰老”中的作用
- 批准号:
497927 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Deciphering the role of osteopontin in the aging eye and age-related macular degeneration
破译骨桥蛋白在眼睛老化和年龄相关性黄斑变性中的作用
- 批准号:
10679287 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Role of AGE/RAGEsignaling as a driver of pathological aging in the brain
AGE/RAGE信号传导作为大脑病理性衰老驱动因素的作用
- 批准号:
10836835 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Elucidation of the protein kinase NLK-mediated aging mechanisms and treatment of age-related diseases
阐明蛋白激酶NLK介导的衰老机制及年龄相关疾病的治疗
- 批准号:
23K06378 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Underlying mechanisms of age-related changes in ingestive behaviors: From the perspective of the aging brain and deterioration of the gustatory system.
与年龄相关的摄入行为变化的潜在机制:从大脑老化和味觉系统退化的角度来看。
- 批准号:
23K10845 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Targeting Age-Activated Proinflammatory Chemokine Signaling by CCL2/11 to Enhance Skeletal Muscle Regeneration in Aging
通过 CCL2/11 靶向年龄激活的促炎趋化因子信号传导以增强衰老过程中的骨骼肌再生
- 批准号:
478877 - 财政年份:2023
- 资助金额:
$ 4.62万 - 项目类别:
Operating Grants














{{item.name}}会员




