Regulation of Renal Xenobiotic Transport by Estrogens

雌激素对肾脏异生物质转运的调节

基本信息

  • 批准号:
    7115801
  • 负责人:
  • 金额:
    $ 20.79万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-09-01 至 2008-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Secretion of substrates from the blood into the urine by the renal proximal tubule plays an essential role for removal of potentially hazardous xenobiotics from the systemic circulation and out of the body. Many such xenobiotics are organic anion substrates and may, therefore, be cleared via interaction with the basolateral membrane organic anion transport (OAT) pathway. Recently, attention has been given to the study of cellular regulation of the OAT pathways, particularly OAT1- and OAT3-mediated transport. Knowledge of the regulation of OAT1 and OAT3 has much practical significance since factors that either suppress or prevent organic anion transport may increase exposure to dangerous xenobiotics to produce or at least exacerbate toxicity, whereas factors that stimulate organic anion secretion may be employed to enhance xenobiotic excretion to reduce environmental exposure. Studies have demonstrated that regulation by various hormonal systems modulates the expression and physiological function of various transport processes in the proximal tubule of the kidney. The sex steroid hormones testosterone and estrogen may serve to upregulate or down regulate, respectively, renal organic anion transport and may account for sex-related differences in xenobiotic accumulation, excretion and response to toxicity. The decrease in organic anion transport associated with estrogen was reported in several studies to be related to an increased susceptibility to toxicity. In spite of the manifestation of gender-related differences in xenobiotic transport, little is understood about sex steroid hormone modulation of transport, particularly estrogens. Also, the presence of various endocrine disrupting chemicals (EDCs), environmental chemicals that possess sex steroid hormone and particularly estrogenic activity (i.e., xenoestrogens) may, through their estrogenic effects, down regulate various transporters involved in renal accumulation and excretion of xenobiotics. To this end the proposal will address the following overall objectives: 1) To characterize the effect of endogenous estrogen, 17beta-estradiol and the environmental xenoestrogens such as diethylstilbestrol (DES) and genistein on renal proximal tubule organic anion transport (OAT1 and OAT3) and 2) to determine the mechanisms by which these estrogens mediate their regulatory control of transport.
性状(由申请方提供):通过肾近端小管将底物从血液分泌到尿液中,对于将潜在危险的外源性物质从体循环中清除并排出体外起着重要作用。 许多这样的外源性物质是有机阴离子底物,因此可以通过与基底外侧膜有机阴离子转运(OAT)途径相互作用而被清除。 最近,注意力已经给予OAT途径的细胞调节的研究,特别是OAT 1和OAT 3介导的运输。 了解OAT 1和OAT 3的调控具有重要的实际意义,因为抑制或阻止有机阴离子转运的因素可能会增加对危险的外源性物质的暴露,从而产生或至少加剧毒性,而刺激有机阴离子分泌的因素可能会增加外源性物质的排泄,以减少环境暴露。 研究表明,各种激素系统的调节调节肾脏近端小管中各种转运过程的表达和生理功能。 性类固醇激素睾酮和雌激素可能分别用于上调或下调肾有机阴离子转运,并可能解释异生物质蓄积、排泄和毒性反应的性别相关差异。 在几项研究中报告了与雌激素相关的有机阴离子转运的减少与对毒性的敏感性增加有关。 尽管表现出与性别有关的差异,外源性物质的运输,很少有人了解性类固醇激素的调制运输,特别是雌激素。此外,各种内分泌干扰化学品(EDCs)的存在,具有性类固醇激素和特别是雌激素活性的环境化学品(即,外源性雌激素)可以通过它们的雌激素效应下调参与外源性物质的肾积累和排泄的各种转运蛋白。 为此,该提案将解决以下总体目标:1)表征内源性雌激素、17 β-雌二醇和环境外源性雌激素(如己烯雌酚(DES)和染料木黄酮)对肾近端小管有机阴离子转运(OAT 1和OAT 3)的影响; 2)确定这些雌激素介导其转运调控的机制。

项目成果

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STEPHEN H WRIGHT其他文献

STEPHEN H WRIGHT的其他文献

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{{ truncateString('STEPHEN H WRIGHT', 18)}}的其他基金

Molecular Organization of the Organic cation-Proton Exchanger, MATE1
有机阳离子-质子交换器的分子组织,MATE1
  • 批准号:
    7873465
  • 财政年份:
    2009
  • 资助金额:
    $ 20.79万
  • 项目类别:
Molecular Organization or Renal Organic Anion Transport
分子组织或肾脏有机阴离子转运
  • 批准号:
    7569334
  • 财政年份:
    2006
  • 资助金额:
    $ 20.79万
  • 项目类别:
Molecular Organization or Renal Organic Anion Transport
分子组织或肾脏有机阴离子转运
  • 批准号:
    7347555
  • 财政年份:
    2006
  • 资助金额:
    $ 20.79万
  • 项目类别:
Molecular Organization of Renal Organic Anion Transport
肾脏有机阴离子转运的分子组织
  • 批准号:
    7027896
  • 财政年份:
    2006
  • 资助金额:
    $ 20.79万
  • 项目类别:
Molecular Organization or Renal Organic Anion Transport
分子组织或肾脏有机阴离子转运
  • 批准号:
    7172582
  • 财政年份:
    2006
  • 资助金额:
    $ 20.79万
  • 项目类别:
Mechanisms of arsenic transport in kidney & bladder
砷在肾脏中的转运机制
  • 批准号:
    6590735
  • 财政年份:
    2002
  • 资助金额:
    $ 20.79万
  • 项目类别:
Mechanisms of arsenic transport in kidney & bladder
砷在肾脏中的转运机制
  • 批准号:
    6666397
  • 财政年份:
    2002
  • 资助金额:
    $ 20.79万
  • 项目类别:
Mechanisms of arsenic transport in kidney & bladder
砷在肾脏中的转运机制
  • 批准号:
    6577206
  • 财政年份:
    2002
  • 资助金额:
    $ 20.79万
  • 项目类别:
RENAL TRANSPORT OF ORGANIC CHELATORS OF HEAVY METALS
重金属有机螯合剂的肾脏转运
  • 批准号:
    6500207
  • 财政年份:
    2001
  • 资助金额:
    $ 20.79万
  • 项目类别:
RENAL TRANSPORT OF ORGANIC CHELATORS OF HEAVY METALS
重金属有机螯合剂的肾脏转运
  • 批准号:
    6695394
  • 财政年份:
    2001
  • 资助金额:
    $ 20.79万
  • 项目类别:

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