PROJECT 2- MOLECULAR & CELLULAR MECHANISMS AAs

项目 2-分子

基本信息

  • 批准号:
    8069936
  • 负责人:
  • 金额:
    $ 43.8万
  • 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:
    2010-05-05 至 2012-04-30
  • 项目状态:
    已结题

项目摘要

Principal Investigator/Program Director (Last, First, Middle): Grollman, Arthur P DESCRIPTION: PROJECT 2 Aristolochic acid (AA), the principal component of plants belonging to the genus Aristolochiae, is a potent human nephrotoxin and carcinogen. Its toxic effects are targeted primarily to the renal proximal tubule where it causes cellular injury leading to cortical tubulointerstitial fibrosis, and ultimately, chronic renal failure. The pathology of this nephropathy is well defined but little is known about the biochemical mechanisms by which AA exerts its nephrotoxic action or how it promotes organ specific carcinogenesis. We hypothesize that AA and/or one of its metabolites act through two separate and distinct cellular mechanisms; namely, (a) transporter-mediated concentration and metabolism in renal proximal tubule cells, where the toxin induces tubular injury; and (b) by reacting with DMAto form dA- and dG-AA adducts that initiate neoplastic change in urothelial cells. A spectrum of experimental models including whole animal, perfused kidney, isolated renal proximal tubules, and cell culture will be used to identify mechanisms for renal handling of AA and the biochemical pathways used for AA metabolic transformation(s). We will take advantage of naturally occurring mouse strains that are sensitive or resistant to AA toxicity to identify processes associated with relative susceptibility. Isolated perfused rat kidneys, renal proximal tubules isolated from mouse and human kidney, and cell culture models, will be used to examine mechanisms by which AA and its metabolites are transported by, and exert their toxic effects, in the proximal tubule, with a focus on defining the roles of mitochondria and oxidative injury in the nephrotoxic response. Pathways involved in the proximal tubule response to AA in induction of tubulointerstitial fibrosis through epithelial-to-mesenchymal transition, and in the human ureteric urothelial cell response to AA as it relates to DMA damage and carcinogenesis, will be studied by gene array expression profiling and proteomics analysis. The formation and repair of AA-DNA adducts will be explored in vivo with mouse models of AA nephropathy, and in vitro with isolated mouse and human tubules, and human ureteric urothelial cell cultures, with an emphasis on defining mechanisms related to AA nephro- and genotoxicity. Finally, we will identify genes and enzymes involved in activation and detoxification of AA and its metabolites, with the thought that genetic polymorphisms may predispose certain individuals to AA nephropathy and/or urothelial cell cancer by altering the expression or function of these enzymes.
首席研究员/项目主管(最后、第一、中):Grollman, Arthur P

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 }}

SHINYA SHIBUTANI其他文献

SHINYA SHIBUTANI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('SHINYA SHIBUTANI', 18)}}的其他基金

PROJECT 2- MOLECULAR & CELLULAR MECHANISMS AAs
项目 2-分子
  • 批准号:
    7305792
  • 财政年份:
    2007
  • 资助金额:
    $ 43.8万
  • 项目类别:
Genotoxicity of Estrogen Compounds in Endocrine Therapy
内分泌治疗中雌激素化合物的遗传毒性
  • 批准号:
    7106592
  • 财政年份:
    2005
  • 资助金额:
    $ 43.8万
  • 项目类别:
Genotoxicity of Estrogen Compounds in Endocrine Therapy
内分泌治疗中雌激素化合物的遗传毒性
  • 批准号:
    7409606
  • 财政年份:
    2005
  • 资助金额:
    $ 43.8万
  • 项目类别:
Genotoxicity of Estrogen Compounds in Endocrine Therapy
内分泌治疗中雌激素化合物的遗传毒性
  • 批准号:
    7232070
  • 财政年份:
    2005
  • 资助金额:
    $ 43.8万
  • 项目类别:
Genotoxicity of Estrogen Compounds in Endocrine Therapy
内分泌治疗中雌激素化合物的遗传毒性
  • 批准号:
    6917467
  • 财政年份:
    2005
  • 资助金额:
    $ 43.8万
  • 项目类别:
Genotoxicity of Estrogen Compounds in Endocrine Therapy
内分泌治疗中雌激素化合物的遗传毒性
  • 批准号:
    7618442
  • 财政年份:
    2005
  • 资助金额:
    $ 43.8万
  • 项目类别:
Mutagenic hot spots & 3-D structure of damaged DNA
诱变热点
  • 批准号:
    6575677
  • 财政年份:
    2002
  • 资助金额:
    $ 43.8万
  • 项目类别:
Mutagenic hot spots & 3-D structure of damaged DNA
诱变热点
  • 批准号:
    6443872
  • 财政年份:
    2001
  • 资助金额:
    $ 43.8万
  • 项目类别:
Mutagenic hot spots & 3-D structure of damaged DNA
诱变热点
  • 批准号:
    6301315
  • 财政年份:
    2000
  • 资助金额:
    $ 43.8万
  • 项目类别:
Mutagenic hot spots & 3-D structure of damaged DNA
诱变热点
  • 批准号:
    6352910
  • 财政年份:
    2000
  • 资助金额:
    $ 43.8万
  • 项目类别:

相似海外基金

The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
  • 批准号:
    EP/Z000920/1
  • 财政年份:
    2025
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
  • 批准号:
    FT230100276
  • 财政年份:
    2024
  • 资助金额:
    $ 43.8万
  • 项目类别:
    ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
  • 批准号:
    MR/X024261/1
  • 财政年份:
    2024
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
  • 批准号:
    DE240100388
  • 财政年份:
    2024
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Discovery Early Career Researcher Award
Zootropolis: Multi-species archaeological, ecological and historical approaches to animals in Medieval urban Scotland
Zootropolis:苏格兰中世纪城市动物的多物种考古、生态和历史方法
  • 批准号:
    2889694
  • 财政年份:
    2023
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Studentship
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
  • 批准号:
    2842926
  • 财政年份:
    2023
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
  • 批准号:
    NC/X001644/1
  • 财政年份:
    2023
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Training Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
  • 批准号:
    2337595
  • 财政年份:
    2023
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Continuing Grant
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
  • 批准号:
    2232190
  • 财政年份:
    2023
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
  • 批准号:
    23K17514
  • 财政年份:
    2023
  • 资助金额:
    $ 43.8万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了