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
- 来源:
- 关键词:AddressAffectAgingAgonistAntioxidantsBile fluidBiliaryBloodBlood GlucoseCaloric RestrictionCellsChemical ExposureChemicalsCyclic AMPCyclic AMP-Dependent Protein KinasesDataData AnalysesDeacetylaseDevelopmentDietDiet ModificationDietary intakeDiseaseDoseEndocrine disruptionEnvironmental ExposureEnvironmental PollutantsEnzymesEthnic OriginExcretory functionExposure toFastingFoodGene ExpressionGene TargetingGenesGenetic TranscriptionGlucagonGluconeogenesisGlucoseGlucuronidesHealthHepaticHepatocyteHumanKnockout MiceLife StyleLiverLongevityMeasuresMediatingMetabolicMultidrug Resistance-Associated ProteinsMusNuclearNutrientNutritional statusPathway interactionsPeroxisome ProliferatorsPilot ProjectsPlasticsPredispositionProcessProductionPropertyProteinsRattusRegulationReporterResveratrolRiskS cerevisiae MRP2 proteinSmall Interfering RNATransgenic OrganismsUp-RegulationUrineViralWestern BlottingYeastsabstractingage effectage relatedanti agingbisphenol Adeprivationenvironmental chemicalfeedinggene inductionglucose productionimprovedin vivoinsightliver functionmRNA Expressionnovelnutritionpentabromodiphenyl etherpreventprotein expressionred winetoxicanttrans-resveratroltranscription factoruptakeurinary
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
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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