Effect of nutritional status on MRP2 expression and biliary excretion of bispheno

营养状况对MRP2表达和双酚胆汁排泄的影响

基本信息

  • 批准号:
    8282836
  • 负责人:
  • 金额:
    $ 36.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-09-08 至 2014-05-31
  • 项目状态:
    已结题

项目摘要

Abstract Hepatic biliary excretion is an essential process that exists to aid the in the elimination of foreign chemicals, and protects the body from accumulating chemicals and toxicants. Understanding the underlying processes by which specific transporters that aid in biliary excretion are regulated is integral for improving human health, predicting chemical exposure, and preventing disease associated with chemical exposure. Nutrition (i.e. dietary intake, fasting, and caloric restriction [CR]) is an important factor in the susceptibility/progression of a variety of diseases associated, especially those associated with aging and environmental exposure. Trans- resveratrol (RES) is an antioxidant in red wine with anti-aging effects that mimic CR, and is an agonist for the deacetylase Sirt1. Understanding how RES, fasting, and CR regulate the expression and function of liver transporters involved in hepatic excretion (i.e. Multidrug Resistance-Associated Proteins [MRPS]) is important for understanding mechanisms by which nutrition is beneficial against chemical exposure and disease. Preliminary data demonstrates that RES increases the mRNA and protein expression of Mrp1-4, 6 in human hepatocytes and mouse liver along with induction of genes regulated by the transcription factor Nuclear Factor- E2-Related Factor 2 (NRF2), suggesting that RES activates human and mouse NRF2. Additionally, liver Mrp1, 2, and 3 expression, along with Ho-1 expression is increased during fasting, in which liver cAMP is increased and Protein Kinase A (PKA) is activated. Furthermore, constitutive activation of NRF2 in livers of KEAP1-null mice results in increased Mrp1-5 expression. The hypothesis of this proposal is that RES, fasting, and CR induce expression of MRPs through Sirt1- and PKA- upstream regulation of NRF2-mediated transcription. Specific aims will determine whether 1) RES treatment induces MRP expression in human hepatocytes and mouse liver through NRF2, 2) fasting and CR induce MRP expression via uptream activation of PKA and downstream activation of Nrf2, 3) RES, fasting, and CR induce MRP via Sirt1, and 4) RES, fasting, and CR affect bisphenol A and PBDE disposition in mice. Together, these studies will define mechanisms by which nutritional status alters expression of human and mouse MRPS, as well as demonstrate whether nutritional status enhances biliary excretion of environmental chemicals. Moreover, they will also provide novel insights into mechanisms that regulate NRF2-induction of human MRP genes. Project Narrative Nutritional status is an important factor for the development of many age-related diseases. Some environmental chemicals are thought to exacerbate or contribute to the development/progression of age- related diseases. The purpose of this project is to determine whether nutrition affects mechanisms involved in the liver's ability to uptake and clear environmental chemicals from the body.
摘要

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Pharmacy research at URI: mining red maple (Acer rubrum) trees for novel therapeutics to manage diabetes.
URI 的药学研究:开采红枫树以寻找治疗糖尿病的新疗法。
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Seeram,Navindra;Xu,Jialin;Li,Liya;Slitt,Angela
  • 通讯作者:
    Slitt,Angela
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Angela L Slitt其他文献

Angela L Slitt的其他文献

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{{ truncateString('Angela L Slitt', 18)}}的其他基金

Mechanisms of Exposure
暴露机制
  • 批准号:
    10704013
  • 财政年份:
    2017
  • 资助金额:
    $ 36.17万
  • 项目类别:
Mechanisms of Exposure
暴露机制
  • 批准号:
    10352512
  • 财政年份:
    2017
  • 资助金额:
    $ 36.17万
  • 项目类别:
Research Experience and Training Coordination Core (RETCC)
研究经验和培训协调核心(RETCC)
  • 批准号:
    10704031
  • 财政年份:
    2017
  • 资助金额:
    $ 36.17万
  • 项目类别:
Sources, Transport, Exposure and Effects of PFASs (STEEP)
PFAS 的来源、传输、暴露和影响 (STEEP)
  • 批准号:
    9258544
  • 财政年份:
    2017
  • 资助金额:
    $ 36.17万
  • 项目类别:
Research Experience and Training Coordination Core (RETCC)
研究经验和培训协调核心(RETCC)
  • 批准号:
    10352517
  • 财政年份:
    2017
  • 资助金额:
    $ 36.17万
  • 项目类别:
Developmental exposure to Bisphenol A and susceptibility to liver injury
发育时期接触双酚 A 和对肝损伤的易感性
  • 批准号:
    8879721
  • 财政年份:
    2015
  • 资助金额:
    $ 36.17万
  • 项目类别:
RESVERATROL INDUCTION OF GENE EXPRESSION VIA ACTIVATION OF CAR AND NRF2
白藜芦醇通过激活 CAR 和 NRF2 诱导基因表达
  • 批准号:
    7960141
  • 财政年份:
    2009
  • 资助金额:
    $ 36.17万
  • 项目类别:
Effect of nutritional status on MRP2 expression and biliary excretion of bispheno
营养状况对MRP2表达和双酚胆汁排泄的影响
  • 批准号:
    7911148
  • 财政年份:
    2009
  • 资助金额:
    $ 36.17万
  • 项目类别:
RESVERATROL INDUCTION OF GENE EXPRESSION VIA ACTIVATION OF CAR AND NRF2
白藜芦醇通过激活 CAR 和 NRF2 诱导基因表达
  • 批准号:
    7725156
  • 财政年份:
    2008
  • 资助金额:
    $ 36.17万
  • 项目类别:
Effect of nutritional status on MRP2 expression and biliary excretion of bispheno
营养状况对MRP2表达和双酚胆汁排泄的影响
  • 批准号:
    7684045
  • 财政年份:
    2008
  • 资助金额:
    $ 36.17万
  • 项目类别:

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激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
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