Junctophilin-2 cleavage in ischemic heart disease
缺血性心脏病中的 Junctophilin-2 裂解
基本信息
- 批准号:10614525
- 负责人:
- 金额:$ 58.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAffectAlternative SplicingAreaBindingC-terminalCalpainCardiacCardiac MyocytesCause of DeathCell NucleusCell membraneCo-ImmunoprecipitationsComplexCouplingDNADataDevelopmentDisabled PersonsDiseaseDisease modelEnsureEnzymesExperimental ModelsFailureGenetic TranscriptionGoalsHeartHeart failureInjuryIschemiaKnock-in MouseLeadLengthMediatingModelingMolecularMusMutationMyocardialMyocardial InfarctionMyocardial IschemiaN-terminalNuclearNuclear Localization SignalNuclear TranslocationPatientsPeptidesPhysiologicalProtein IsoformsProteinsProteolysisRNARNA SplicingReperfusion InjuryReperfusion TherapyRoleSRSF2 geneSarcoplasmic ReticulumSiteStructural ProteinTestingUnited StatesVentricular RemodelingWorkcalmodulin-dependent protein kinase IIimprovedin vivoischemic injuryjunctophilinlink proteinm-calpainmRNA Precursormouse modelnoveloverexpressionpreventstress reduction
项目摘要
PROJECT SUMMARY / ABSTRACT
Ischemic heart disease is a major cause of death in the United States. At the cellular level, myocardial
ischemia alters excitation-contraction coupling and promoted the development of heart failure. Junctophilin-2
(JPH2) is an inter-membrane linker protein that maintains the plasmalemma and sarcoplasmic reticulum (SR)
at a fixed distance to facilitate excitation-contraction coupling. Ischemia/reperfusion injury and ischemic heart
disease lead to a loss of JPH2 protein levels, which in part is caused by proteolysis by the Ca2+-sensitive
enzyme calpain. Our long-term goal of this project is to elucidate the molecular and cellular mechanisms by
which calpain causes JPH2 cleavage and how the ensuing JPH2 C-terminal peptide alters myocardial function.
We will test the central hypothesis that calpain cleaves JPH2 to release a C-terminal peptide that traffics into
the cardiomyocyte nucleus where it alters CaMKII-d splicing which affects myocardial remodeling.
项目摘要/摘要
在美国,缺血性心脏病是主要的死亡原因。在细胞水平上,心肌
缺血改变兴奋-收缩偶联,促进心力衰竭的发展。结膜蛋白-2
(JPH2)是维持质膜和肌浆网(SR)的膜间连接蛋白。
在固定的距离,以便于激发-收缩耦合。缺血/再灌注损伤与缺血心脏
疾病导致JPH2蛋白水平下降,这在一定程度上是由于对钙敏感的蛋白质分解引起的
钙解酶。我们这个项目的长期目标是通过以下方式阐明分子和细胞机制
哪种钙蛋白酶导致JPH2裂解,以及随后的JPH2 C端肽如何改变心肌功能。
我们将测试中央假设,即Calain裂解JPH2释放一种C-末端多肽,该C-末端多肽可以运输到
心肌细胞核,它改变了CaMKII-d剪接,从而影响心肌重塑。
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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Xander H.T. Wehrens其他文献
Regulation of the RyR2 Calcium Release Channel by SPEG
- DOI:
10.1016/j.bpj.2018.11.2495 - 发表时间:
2019-02-15 - 期刊:
- 影响因子:
- 作者:
Xander H.T. Wehrens - 通讯作者:
Xander H.T. Wehrens
PO-675-03 HIGH PROTEIN DIET-PROMOTES ATRIAL FIBRILLATION BY ACTIVATING AIM2 INFLAMMASOME
- DOI:
10.1016/j.hrthm.2022.03.451 - 发表时间:
2022-05-01 - 期刊:
- 影响因子:5.700
- 作者:
Jia Song;Xiaolei Wang;Yuriana Aguilar-Sanchez;Luge Li;Xander H.T. Wehrens;Na Li - 通讯作者:
Na Li
GW25-e5168 Impaired Post-Transcriptional Regulation of RyR2 by microRNA-106b-25 Cluster Promotes Atrial Fibrillation
- DOI:
10.1016/j.jacc.2014.06.284 - 发表时间:
2014-10-21 - 期刊:
- 影响因子:
- 作者:
Na Li;David Y. Chiang;Niels Voigt;James F. Martin;Dobromir Dobrev;Xander H.T. Wehrens - 通讯作者:
Xander H.T. Wehrens
Ca SR Leak is Modulated by CaMKII Phosphorylation on RyR2-S2814
- DOI:
10.1016/j.bpj.2009.12.1648 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
Yi Yang;Laetitia Pereira;Ralph J. van Oort;Xander H.T. Wehrens;Donald M. Bers - 通讯作者:
Donald M. Bers
Inhibition of PKA Phosphorylation of RyR2 Improves Excitation-Contraction Coupling in Dystrophic Cardiomyopathy
- DOI:
10.1016/j.hrthm.2009.09.047 - 发表时间:
2009-11-01 - 期刊:
- 影响因子:
- 作者:
Na Li;Satyam Sarma;Ralph J. van Oort;Darlene Skapura;Xander H.T. Wehrens - 通讯作者:
Xander H.T. Wehrens
Xander H.T. Wehrens的其他文献
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{{ truncateString('Xander H.T. Wehrens', 18)}}的其他基金
Role of Nucleoside-Diphosphate Kinase Signaling in Atrial Fibrillation
核苷二磷酸激酶信号传导在心房颤动中的作用
- 批准号:
10594130 - 财政年份:2023
- 资助金额:
$ 58.64万 - 项目类别:
Junctophilin-2 cleavage in ischemic heart disease
缺血性心脏病中的 Junctophilin-2 裂解
- 批准号:
10210774 - 财政年份:2021
- 资助金额:
$ 58.64万 - 项目类别:
Junctophilin-2 cleavage in ischemic heart disease
缺血性心脏病中的 Junctophilin-2 裂解
- 批准号:
10375580 - 财政年份:2021
- 资助金额:
$ 58.64万 - 项目类别:
Determining the Role of Junctophilin-2 in Cardiac Disease
确定 Junctophilin-2 在心脏病中的作用
- 批准号:
8901684 - 财政年份:2014
- 资助金额:
$ 58.64万 - 项目类别:
Determining the Role of Junctophilin-2 in Cardiac Disease
确定 Junctophilin-2 在心脏病中的作用
- 批准号:
9102541 - 财政年份:2014
- 资助金额:
$ 58.64万 - 项目类别:
Determining the Role of Junctophilin-2 in Cardiac Disease
确定 Junctophilin-2 在心脏病中的作用
- 批准号:
9041670 - 财政年份:2014
- 资助金额:
$ 58.64万 - 项目类别:
Determining the Role of Junctophilin-2 in Cardiac Disease
确定 Junctophilin-2 在心脏病中的作用
- 批准号:
8828771 - 财政年份:2014
- 资助金额:
$ 58.64万 - 项目类别:
Determining the Role of Junctophilin-2 in Cardiac Disease
确定 Junctophilin-2 在心脏病中的作用
- 批准号:
8710750 - 财政年份:2014
- 资助金额:
$ 58.64万 - 项目类别:
Regulation of Sarcoplasmic Reticulum Calcium Release in Heart Failure
心力衰竭肌浆网钙释放的调节
- 批准号:
9234581 - 财政年份:2009
- 资助金额:
$ 58.64万 - 项目类别:
CaMKII Regulation of Cardiac Ryanodine Receptors in Atrial Fibrillation
CaMKII 对心房颤动中心脏兰尼定受体的调节
- 批准号:
7837367 - 财政年份:2009
- 资助金额:
$ 58.64万 - 项目类别:
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