MECHANISM OF RENAL TUBULAR ANION TRANSPORT
肾小管阴离子转运机制
基本信息
- 批准号:6413604
- 负责人:
- 金额:$ 24.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-12-01 至 2001-11-30
- 项目状态:已结题
- 来源:
- 关键词:Xenopus oocyte apical membrane brush border membrane cell line chimeric proteins chloride ion complementary DNA formates gene targeting genetically modified animals guinea pigs immunoaffinity chromatography ion transport laboratory mouse laboratory rat liposomes membrane permeability membrane transport proteins molecular cloning oxalates protein isoforms protein structure function renal tubular transport sodium bicarbonate
项目摘要
The principal focus of this project continues to be the mechanisms of
anion transport in the proximal tubule. Studies during the past decade
have supported a model by which transcellular CI-absorption in the
proximal tubule involves uphill CI-uptake across the luminal membrane by
exchange with formate and oxalate. Recycling of formate occurs by H/+-
couple formate transport in parallel with Na/+-H/+ exchange, whereas next
project period we propose to investigate two aspects of proximal tubule
anion transport. First, we plan to complete the cDNA cloning and carry out
the physiological characterization of a novel transporter that is likely
to play a role in mediating apical membrane anion transport. Specifically,
we will isolate, clone and sequence cDNAs encoding the transporter,
determine anion specificity and transport modes by functional expression
in Xenopus oocytes; general specific antibodies, and determine cell and
membrane sites of expression; determine whether different isoforms of the
transporter exist; examine structure-function relationships by use of
chimeric constructs; and estimate the contribution of the transporter to
integrated tubule function in microperfusion studies in mice with targeted
disruption of the transporter gene. Second, in collaboration with Gerhard
Giebisch (project#1), we propose to continue studies of the mechanisms of
regulation of transcellular NaHCO/3 and NaCI reabsorption in the proximal
tubule. Specifically, we will measure the activities of both anion
exchanges (CI-formate and CI-oxalate) and recycling pathways (H+-coupled
formate transport, Na/+- sulfate co-transport, oxalate-sulfate exchange)
in renal brush border vesicles isolated from rats subjects to conditions
that regulate proximal NaHCO/3 and NaCI reabsorption (eg. metabolic
acidosis, hypokalemic alkalosis, furosemide-induced volume contraction).
Activities of these pathways in membrane vesicles will be correlated with
rates of transtubular HCO/3- and CI- reabsorption in the intact tubule
under similar conditions. We will thereby test the hypothesis that
activities of luminal membrane anion transporters are appropriate altered
tot permit independent regulation of proximal tubule NaHCO/3 and NaCI
reabsorption. The proposed project will provide new information on the
molecular mechanisms and regulation of renal CI- transport, and is
therefore of relevance for understanding clinical disorders of NaCI
balance.
该项目的主要重点仍然是
阴离子在近端小管中的运输。过去十年的研究
支持了一种模型,通过该模型,
近端小管涉及跨腔膜的上行CI摄取
与甲酸盐和草酸盐进行交换。甲酸盐的循环是通过H/+-
与Na/+-H/+交换平行地耦合甲酸盐转运,而下一步
在项目期间,我们建议从两个方面研究近端小管
负离子传输。首先,我们计划完成cdna的克隆并进行
一种新的转运蛋白的生理特性
在介导根尖膜阴离子转运中发挥作用。具体来说,
我们将分离、克隆和测序编码转运蛋白的cDNA,
通过功能表达确定阴离子的专一性和转运方式
在非洲爪哇卵母细胞中;通用特异性抗体,并测定细胞和
膜表达部位;确定不同亚型的
传输器存在;使用检查结构-功能关系
嵌合结构;并估计转运体对
靶向性小鼠微灌注研究中的综合肾小管功能
转运蛋白基因的破坏。第二,与格哈德合作
GieBisch(项目1),我们建议继续研究
近端跨细胞NaHCO/3和NaCI重吸收的调节
小管。具体地说,我们将测量两个阴离子的活性
交换(CI-甲酸盐和CI-草酸盐)和循环途径(H+偶联
甲酸盐转运、Na/+-硫酸盐共转运、草酸盐-硫酸盐交换)
分离的大鼠肾刷状缘囊泡中
调节近端NaHCO/3和NaCI重吸收(例如。代谢性
酸中毒、低钾性碱中毒、速尿引起的容量收缩)。
这些途径在膜泡中的活动将与
肾小管内HCO/3-和CI-重吸收的速率
在类似的条件下。因此,我们将检验这一假设
腔膜阴离子转运体活性适当改变
TOT允许独立调节近端小管NaHCO/3和NaCI
重吸收。拟议的项目将提供有关
肾CI转运的分子机制及其调控
因此,了解NACI的临床障碍具有重要意义
平衡。
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 }}
PETER S. ARONSON其他文献
PETER S. ARONSON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('PETER S. ARONSON', 18)}}的其他基金
Short Term Research Training: Students in Health Professional Schools
短期研究培训:卫生专业学校的学生
- 批准号:
9274967 - 财政年份:2015
- 资助金额:
$ 24.29万 - 项目类别:
Short Term Research Training: Students in Health Professional Schools
短期研究培训:卫生专业学校的学生
- 批准号:
10405426 - 财政年份:2015
- 资助金额:
$ 24.29万 - 项目类别:
Short Term Research Training: Students in Health Professional Schools
短期研究培训:卫生专业学校的学生
- 批准号:
10620350 - 财政年份:2015
- 资助金额:
$ 24.29万 - 项目类别:
Roles of SLC26A6 in Renal NaCI Transport and Prevention of Oxalate Urolithiasis
SLC26A6 在肾 NaCl 转运和预防草酸尿石症中的作用
- 批准号:
7850073 - 财政年份:2009
- 资助金额:
$ 24.29万 - 项目类别:
Roles of SLC26A6 in Renal NaCI Transport and Prevention of Oxalate Urolithiasis
SLC26A6 在肾 NaCl 转运和预防草酸尿石症中的作用
- 批准号:
7921096 - 财政年份:2009
- 资助金额:
$ 24.29万 - 项目类别:
相似海外基金
Structural diversity of ceramide moiety responsible for apical membrane function of bladder transitional epithelial cells
负责膀胱移行上皮细胞顶膜功能的神经酰胺部分的结构多样性
- 批准号:
23K08792 - 财政年份:2023
- 资助金额:
$ 24.29万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Epithelial apical membrane polarization, morphogenesis, and regulation of gene expression
上皮顶膜极化、形态发生和基因表达调控
- 批准号:
BB/X000575/1 - 财政年份:2023
- 资助金额:
$ 24.29万 - 项目类别:
Research Grant
Three dimensional dynamics of apical membrane ruffles on living cells by scanning ion conductance microscopy
通过扫描离子电导显微镜观察活细胞顶膜皱褶的三维动力学
- 批准号:
17K15541 - 财政年份:2017
- 资助金额:
$ 24.29万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Anti-Malarial Agents Targeting Apical Membrane Antigen 1
针对顶膜抗原 1 的抗疟药
- 批准号:
nhmrc : GNT1098884 - 财政年份:2016
- 资助金额:
$ 24.29万 - 项目类别:
Project Grants
changed folic acid metabolic pathway and apical membrane of urinary bladder is one cause of chronic ischemia related lower urinary tract dysfunction.
叶酸代谢途径和膀胱顶膜的改变是慢性缺血相关下尿路功能障碍的原因之一。
- 批准号:
16K20150 - 财政年份:2016
- 资助金额:
$ 24.29万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Anti-Malarial Agents Targeting Apical Membrane Antigen 1
针对顶膜抗原 1 的抗疟药
- 批准号:
nhmrc : 1098884 - 财政年份:2016
- 资助金额:
$ 24.29万 - 项目类别:
Project Grants
Regulation of epithelial apical membrane differentiation and function
上皮顶膜分化和功能的调节
- 批准号:
BB/L007584/1 - 财政年份:2014
- 资助金额:
$ 24.29万 - 项目类别:
Research Grant
A New Class of Anti-Malarial Agents Targetting Apical Membrane Antigen
一类针对顶膜抗原的新型抗疟疾药物
- 批准号:
nhmrc : 1025150 - 财政年份:2012
- 资助金额:
$ 24.29万 - 项目类别:
Project Grants
How reciprocal regulation of the cell-cell adhesion and the apical membrane defines a unified epithelial system via the cytoskeleton and cell signaling in epithelial cell sheets
细胞间粘附和顶膜的相互调节如何通过上皮细胞片中的细胞骨架和细胞信号传导定义统一的上皮系统
- 批准号:
24247037 - 财政年份:2012
- 资助金额:
$ 24.29万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Functional analysis of the "Apical Membrane Antigen 1": Investigating the role of phosphorylation of the blood-stage vaccine candidate in the malaria parasite Plasmodium falciparum
“顶膜抗原 1”的功能分析:研究血液阶段候选疫苗磷酸化在疟疾寄生虫恶性疟原虫中的作用
- 批准号:
161304732 - 财政年份:2010
- 资助金额:
$ 24.29万 - 项目类别:
Research Grants