Role and function of prohibitin in intestinal inflammation

抑制素在肠道炎症中的作用和功能

基本信息

  • 批准号:
    8418743
  • 负责人:
  • 金额:
    $ 14.65万
  • 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:
    2010-02-15 至 2015-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Prohibitin is a highly conserved protein that has pleiotropic functions depending on the cell and tissue type in which it is expressed. Little is known regarding the expression and function of prohibitin in the intestine. During my postdoctoral fellowship I demonstrated that 1) prohibitin is expressed by native human colonic epithelia as well as model intestinal epithelial cells, 2) in resting intestinal epithelial cells, prohibitin localizes to the mitochondria and protects against oxidative stress, 3) prohibitin is downregulated during oxidant stress, during active human inflammatory bowel disease (IBD) and experimental colitis, and 4) prohibitin transgenic mice are protected from DSS- and Salmonella typhimurium-induced colitis and oxidative stress. In assessing the mechanism by which prohibitin modulates inflammation, our preliminary data demonstrate that prohibitin is a potent activator of Nrf2, a master transcriptional regulator that activates a battery of anti-oxidant genes. In addition, our recent in vitro data demonstrate that prohibitin inhibits TNF(-induced NF-(B activation and barrier dysfunction. Based on these data, the central hypothesis of this proposal is that prohibitin functions as an epithelial defense against oxidative stress and inflammation-induced barrier dysfunction and decreased levels of prohibitin in IBD contribute to tissue injury and inflammation. The overall objective of the proposal is to determine the mechanism underlying the protective role of prohibitin in colitis. Our interrelated yet independently achievable aims based on our hypothesis and supported by preliminary data are i) to determine the role and mechanism by which prohibitin modulates Nrf2, ii) to address the mechanism of prohibitin in inhibiting NF-(B signaling and its downstream effects, and iii) to determine the in vivo mechanism by which prohibitin ameliorates colitis Together, these studies will elucidate the function and mechanism of action of prohibitin as an activator of anti-oxidants and as an anti-inflammatory molecule in intestinal epithelial cells. The training in protein biochemistry and electrophysiology the candidate will learn from executing the proposed studies will improve potential for transition to an independent IBD researcher.
描述(由申请人提供): Prohibitin是一种高度保守的蛋白质,其具有多效性功能,这取决于其表达的细胞和组织类型。关于抑制素在肠道中的表达和功能知之甚少。在我的博士后研究期间,我证明了1)抑制素由天然人结肠上皮细胞以及模型肠上皮细胞表达,2)在静息肠上皮细胞中,抑制素定位于线粒体并保护免受氧化应激,3)抑制素在氧化应激期间下调,在活动性人类炎症性肠病(IBD)和实验性结肠炎期间,和4)抑制素转基因小鼠被保护免于DSS和鼠伤寒沙门氏菌诱导的结肠炎和氧化应激。在评估prohibitin调节炎症的机制时,我们的初步数据表明,prohibitin是Nrf 2的有效激活剂,Nrf 2是激活一系列抗氧化基因的主转录调节因子。此外,我们最近的体外实验数据表明,抑制素抑制TNF-α诱导的NF-β B活化和屏障功能障碍。基于这些数据,该提议的中心假设是,抑制素作为上皮防御氧化应激和炎症诱导的屏障功能障碍的功能,并且IBD中抑制素水平的降低有助于组织损伤和炎症。该提案的总体目标是确定抑制素在结肠炎中的保护作用的机制。基于我们的假设和初步数据的支持,我们相互关联但独立可实现的目标是:i)确定prohibitin调节Nrf 2的作用和机制,ii)解决prohibitin抑制NF-κ B的机制。(B)信号传导及其下游效应,和iii)确定抑制素改善结肠炎的体内机制。这些研究将阐明抑制素作为抗氧化剂的活化剂和作为肠上皮细胞中的抗炎分子的功能和作用机制。候选人将从执行拟议的研究中学习蛋白质生物化学和电生理学方面的培训,这将提高过渡到独立IBD研究人员的潜力。

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 }}

ARIANNE L THEISS其他文献

ARIANNE L THEISS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('ARIANNE L THEISS', 18)}}的其他基金

Adipose Tissue Extracellular Vesicles in Colorectal Tumorigenesis
脂肪组织细胞外囊泡在结直肠肿瘤发生中的作用
  • 批准号:
    10655305
  • 财政年份:
    2022
  • 资助金额:
    $ 14.65万
  • 项目类别:
Adipose Tissue Extracellular Vesicles in Colorectal Tumorigenesis
脂肪组织细胞外囊泡在结直肠肿瘤发生中的作用
  • 批准号:
    10367993
  • 财政年份:
    2022
  • 资助金额:
    $ 14.65万
  • 项目类别:
Mitochondrial Dysfunction and Mitophagy in Ileitis
回肠炎中的线粒体功能障碍和线粒体自噬
  • 批准号:
    9982322
  • 财政年份:
    2019
  • 资助金额:
    $ 14.65万
  • 项目类别:
Diversity Supplement to R01 Mitochondrial Dysfunction and Mitophagy in Ileitis
R01 回肠炎线粒体功能障碍和线粒体自噬的多样性补充
  • 批准号:
    10443329
  • 财政年份:
    2019
  • 资助金额:
    $ 14.65万
  • 项目类别:
Mitochondrial Dysfunction and Mitophagy in Ileitis
回肠炎中的线粒体功能障碍和线粒体自噬
  • 批准号:
    10557967
  • 财政年份:
    2019
  • 资助金额:
    $ 14.65万
  • 项目类别:
Mitochondrial Dysfunction and Mitophagy in Ileitis
回肠炎中的线粒体功能障碍和线粒体自噬
  • 批准号:
    10450818
  • 财政年份:
    2019
  • 资助金额:
    $ 14.65万
  • 项目类别:
Mitochondrial Dysfunction and Mitophagy in Ileitis
回肠炎中的线粒体功能障碍和线粒体自噬
  • 批准号:
    10219235
  • 财政年份:
    2019
  • 资助金额:
    $ 14.65万
  • 项目类别:
Maintenance of intestinal epithelial cell homeostasis by prohibitin
抑制素维持肠上皮细胞稳态
  • 批准号:
    8737248
  • 财政年份:
    2013
  • 资助金额:
    $ 14.65万
  • 项目类别:
Maintenance of intestinal epithelial cell homeostasis by prohibitin
抑制素维持肠上皮细胞稳态
  • 批准号:
    8633115
  • 财政年份:
    2013
  • 资助金额:
    $ 14.65万
  • 项目类别:
Role and function of prohibitin in intestinal inflammation
抑制素在肠道炎症中的作用和功能
  • 批准号:
    8222138
  • 财政年份:
    2010
  • 资助金额:
    $ 14.65万
  • 项目类别:

相似海外基金

Development of small molecule inhibitors as anti-inflammatory agents and antidotes for arsenicals
开发作为抗炎剂和砷解毒剂的小分子抑制剂
  • 批准号:
    10727507
  • 财政年份:
    2023
  • 资助金额:
    $ 14.65万
  • 项目类别:
Discovery of New Anti-Inflammatory Agents to Treat COPD
发现治疗慢性阻塞性肺病的新型抗炎药
  • 批准号:
    9194162
  • 财政年份:
    2016
  • 资助金额:
    $ 14.65万
  • 项目类别:
Synthesis of anti-inflammatory agents and their structure-activity relationships studies
抗炎药的合成及其构效关系研究
  • 批准号:
    496858-2016
  • 财政年份:
    2016
  • 资助金额:
    $ 14.65万
  • 项目类别:
    University Undergraduate Student Research Awards
NAAA Inhibitors as Anti-inflammatory Agents, Phase II
NAAA 抑制剂作为抗炎剂,II 期
  • 批准号:
    9201955
  • 财政年份:
    2015
  • 资助金额:
    $ 14.65万
  • 项目类别:
Novel flavonoids as anti-inflammatory agents in alcoholism
新型黄酮类化合物作为酒精中毒的抗炎剂
  • 批准号:
    8251289
  • 财政年份:
    2014
  • 资助金额:
    $ 14.65万
  • 项目类别:
TLR-7 Agonists as Targeted Anti-inflammatory Agents in Arthritis
TLR-7 激动剂作为关节炎的靶向抗炎药
  • 批准号:
    8302750
  • 财政年份:
    2012
  • 资助金额:
    $ 14.65万
  • 项目类别:
Design and in vivo delivery of novel anti-inflammatory agents
新型抗炎剂的设计和体内递送
  • 批准号:
    267940
  • 财政年份:
    2012
  • 资助金额:
    $ 14.65万
  • 项目类别:
    Operating Grants
Development of inlammasome inhibitors to be used as anti-inflammatory agents
开发用作抗炎剂的inlammasome抑制剂
  • 批准号:
    8403458
  • 财政年份:
    2012
  • 资助金额:
    $ 14.65万
  • 项目类别:
Development of inlammasome inhibitors to be used as anti-inflammatory agents
开发用作抗炎剂的inlammasome抑制剂
  • 批准号:
    8549297
  • 财政年份:
    2012
  • 资助金额:
    $ 14.65万
  • 项目类别:
TLR-7 Agonists as Targeted Anti-inflammatory Agents in Arthritis
TLR-7 激动剂作为关节炎的靶向抗炎药
  • 批准号:
    8472443
  • 财政年份:
    2012
  • 资助金额:
    $ 14.65万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了