Novel Insights into Ischemic-Induced Cardiac Remodeling

对缺血引起的心脏重塑的新见解

基本信息

  • 批准号:
    10063890
  • 负责人:
  • 金额:
    $ 47.86万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-01-15 至 2022-10-31
  • 项目状态:
    已结题

项目摘要

Project Summary DJ-1 is a cytoprotective protein that is activated by oxidative stress. Due in large part to the association of DJ-1 with Parkinson's Disease, most studies aimed at investigating its role in response to pathological stimuli have been confined to the brain or neuronal cells. However, DJ-1 is expressed in the heart where it also possesses cytoprotective actions. Studies indicate that DJ-1 plays an important role in multiple cellular processes, including oxidative stress response, anti-apoptotic signaling, and transcriptional regulation. However, the cellular mechanisms underlying these reported actions remain largely unknown. Given that DJ-1 is a small, dimeric, single-domain protein, it either possesses multiple functions to account for these actions or there is a single biochemical activity that explains all of them. What is known is that DJ-1 is activated by the removal of a 15-amino acid peptide at its C terminus in response to oxidative stress. We recently provided the first evidence that DJ-1 is activated within hours following the onset of acute myocardial ischemia-reperfusion (I/R). Preliminary studies from our lab demonstrate that cardiac DJ-1 remains active for up to 7 days following the onset of ischemic injury. Furthermore, our studies revealed that DJ-1 deficient mice displayed worse cardiac dysfunction in response to ischemic-induced heart failure compared to wild-type mice. Elevated levels of hypertrophy, fibrosis, and inflammation accompanied the worse cardiac dysfunction in the DJ-1 deficient mice. More importantly, we provide novel evidence that the delivery of the active form of DJ-1 using recombinant adeno-associated virus 9 (AAV9-DJ1WTΔC) reduces the development of ischemic-induced heart failure. This is the first and only demonstration that an active form of DJ-1 provides cytoprotection in an in vivo model of injury. In this proposal, we will expand on our previous findings and attempt to fill knowledge gaps in the literature regarding the cellular actions of DJ-1. 3 specific aims have been proposed. Aim 1 will determine if DJ- 1 is a novel cardiac deglycase that opposes glycative stress. Aim 2 will determine if DJ-1 attenuates ischemic- induced heart failure by promoting the cardioprotective actions of thioredoxin. Aim 3 will determine if DJ-1 opposes TGF-β signaling by regulating the cardiac expression of Arkadia.
项目总结

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart.
  • DOI:
    10.1038/s41598-021-98722-1
  • 发表时间:
    2021-09-30
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Pantner Y;Polavarapu R;Chin LS;Li L;Shimizu Y;Calvert JW
  • 通讯作者:
    Calvert JW
Dynamic Regulation of Cysteine Oxidation and Phosphorylation in Myocardial Ischemia-Reperfusion Injury.
  • DOI:
    10.3390/cells10092388
  • 发表时间:
    2021-09-11
  • 期刊:
  • 影响因子:
    6
  • 作者:
    Casin KM;Calvert JW
  • 通讯作者:
    Calvert JW
Harnessing the Benefits of Endogenous Hydrogen Sulfide to Reduce Cardiovascular Disease.
Impact of Lymphangiogenesis on Cardiac Remodeling After Ischemia and Reperfusion Injury.
  • DOI:
    10.1161/jaha.118.009565
  • 发表时间:
    2018-10-02
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Shimizu Y;Polavarapu R;Eskla KL;Pantner Y;Nicholson CK;Ishii M;Brunnhoelzl D;Mauria R;Husain A;Naqvi N;Murohara T;Calvert JW
  • 通讯作者:
    Calvert JW
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John Winter Calvert其他文献

John Winter Calvert的其他文献

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{{ truncateString('John Winter Calvert', 18)}}的其他基金

Regulation of CSE-Derived Hydrogen Sulfide in the Heart
CSE 衍生的硫化氢在心脏中的调节
  • 批准号:
    10659832
  • 财政年份:
    2023
  • 资助金额:
    $ 47.86万
  • 项目类别:
Novel Insights into Ischemic-Induced Cardiac Remodeling
对缺血引起的心脏重塑的新见解
  • 批准号:
    9934694
  • 财政年份:
    2018
  • 资助金额:
    $ 47.86万
  • 项目类别:
Targeting the orphan nuclear receptor LRH-1 with small molecules
用小分子靶向孤儿核受体 LRH-1
  • 批准号:
    9403854
  • 财政年份:
    2017
  • 资助金额:
    $ 47.86万
  • 项目类别:
Targeting the orphan nuclear receptor LRH-1 with small molecules
用小分子靶向孤儿核受体 LRH-1
  • 批准号:
    10660545
  • 财政年份:
    2017
  • 资助金额:
    $ 47.86万
  • 项目类别:
Targeting the orphan nuclear receptor LRH-1 with small molecules
用小分子靶向孤儿核受体 LRH-1
  • 批准号:
    10681892
  • 财政年份:
    2017
  • 资助金额:
    $ 47.86万
  • 项目类别:
Hydrogen sulfide attenuates heart failure through Nrf2-mediated signaling
硫化氢通过 Nrf2 介导的信号传导减轻心力衰竭
  • 批准号:
    8383492
  • 财政年份:
    2010
  • 资助金额:
    $ 47.86万
  • 项目类别:
Hydrogen sulfide attenuates heart failure through Nrf2-mediated signaling
硫化氢通过 Nrf2 介导的信号传导减轻心力衰竭
  • 批准号:
    7767448
  • 财政年份:
    2010
  • 资助金额:
    $ 47.86万
  • 项目类别:
Hydrogen sulfide attenuates heart failure through Nrf2-mediated signaling
硫化氢通过 Nrf2 介导的信号传导减轻心力衰竭
  • 批准号:
    8011451
  • 财政年份:
    2010
  • 资助金额:
    $ 47.86万
  • 项目类别:
Hydrogen sulfide attenuates heart failure through Nrf2-mediated signaling
硫化氢通过 Nrf2 介导的信号传导减轻心力衰竭
  • 批准号:
    8197419
  • 财政年份:
    2010
  • 资助金额:
    $ 47.86万
  • 项目类别:
Hydrogen sulfide attenuates heart failure through Nrf2-mediated signaling
硫化氢通过 Nrf2 介导的信号传导减轻心力衰竭
  • 批准号:
    8586340
  • 财政年份:
    2010
  • 资助金额:
    $ 47.86万
  • 项目类别:

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