Aquaglyceroporins in Red Blood Cells and Malaria
红细胞和疟疾中的水甘油孔蛋白
基本信息
- 批准号:7600047
- 负责人:
- 金额:$ 15.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1992
- 资助国家:美国
- 起止时间:1992-05-01 至 2012-05-31
- 项目状态:已结题
- 来源:
- 关键词:Cell membraneCellsCessation of lifeChildCountryCulicidaeDiseaseDisruptionErythrocytesFamilyGene TargetingGenesGlycerolGoalsHumanInfectionInsectaInvadedInvestigationKnockout MiceLife Cycle StagesMalariaMembraneMusNull LymphocytesNumbersNutrientOrganismParasitemiaParasitesPathogenicityPathway interactionsPermeabilityPlasmodiumPlasmodium falciparumPreventionProductionRateRattusRelative (related person)RoleSerumStagingTherapeuticUreaWaterWhole OrganismWild Type Mouseaquaporin 3cell typemouse modelmutantsolutetooltransmission processuptakewater channel
项目摘要
DESCRIPTION (provided by applicant): Aquaglyceroporins form a subfamily of the aquaporin water channel family-transporting water, glycerol and urea. Human red blood cells [RBCs] contain the aquaglyceroporin AQP3; mouse RBCs contain AQP9. Plasmodia causing malaria contain aquaglyceroporins -- P. falciparum causes human malaria and expresses PfAQP; P. berghei causes mouse malaria and expresses PbAQP. Glycerol is used by the intracellular malaria parasite [merozoite] for production of glycerolipids. Import of glycerol requires transport of the solute across three membranes - the RBC plasma membrane [PM], the parasitophorous vacuolar membrane [PVM], and the plasmodia plasma membrane [PPM]. We hypothesize that aquaglyceroporins are involved in malarial infection and may provide a new pathway of potential therapeutic importance. Aim I. To understand the contribution of aquaglyceroporins to glycerol transport by RBC membranes, the copy numbers will be determined for AQP3 in human and AQP9 in mouse RBCs. We will also compare the water, glycerol, and urea permeability of aquaglyceroporin null RBCs to wildtype cells. Aim II. The biophysical functions of aquaglyceroporin PbAQP from P. berghei will be characterized. In addition the localization and expression of PbAQP will be defined during the life cycle of the organism. Aim III. Aquaglyceroporin null cells will allow us to understand the role of these channels in malarial infection. The pathogenicity of PbAQP null P. berghei will be compared to that of wildtype parasites. The role of AQP9 will be determined by comparing the parasitemia of wildtype mice to that of AQP9 null mice. The mouse model of malaria will also be evaluated in the insect stages of Plasmodium by studying the expression of PbAQP in the insect and the effect of PbAQP disruption on the proliferation of P. berghei in the mosquito and the transmission of P. berghei from the mosquito to the mouse. Aim IV. Investigation of the human malaria parasite, P. falciparum, will be crucial for understanding roles for aquaglyceroporins in human malarial infection. Human RBCs will be infected with PfAQP null or wildtype P. falciparum, and the parasitemia compared. To determine the role of the human RBC aquaglyceroporins in malaria, parasitemia of wildtype RBCs will be compared to AQP3 null RBCs. Malaria is a major cause of disease and death of children in many underdeveloped countries. The parasites causing malaria invade red blood cells and multiply, causing massive cellular destruction. The goal of this application is to define the pathway for uptake of the nutrient glycerol by red blood cells and malaria parasites, with hope that this may reveal new avenues for prevention or treatment of malaria.
描述(由申请人提供):水准蛋白会形成水通道水通道家庭传输水,甘油和尿素的亚家族。人红细胞[RBC]含有水甘露糖蛋白AQP3;鼠标RBC包含AQP9。引起疟疾的疟原虫含有水甘露糖蛋白 - 恶性疟原虫会引起人类疟疾并表达PFAQP; P. berghei会导致小鼠疟疾并表达PBAQP。甘油由细胞内疟疾寄生虫[Merozoite]用于产生甘油脂蛋白。甘油的进口需要在三个膜上运输溶质 - RBC质膜[PM],寄生虫液泡膜[PVM]和浆膜质膜[PPM]。我们假设水甘露糖蛋白参与疟疾感染,并可能提供潜在的治疗重要性的新途径。目的I.为了了解水甘露糖蛋白对RBC膜的甘油转运的贡献,将确定人类中AQP3的拷贝数和小鼠RBC中的AQP9。我们还将比较水甘露糖蛋白无RBC对野生型细胞的水,甘油和尿素渗透性。目标II。将表征来自P. berghei的水甘露糖蛋白PBAQP的生物物理功能。此外,将在生物体生命周期中定义PBAQP的定位和表达。目标三。水甘露糖蛋白无效细胞将使我们能够了解这些通道在疟疾感染中的作用。 PBAQP null P. berghei的致病性将与野生型寄生虫的致病性进行比较。 AQP9的作用将通过将野生型小鼠的寄生虫与AQP9 NULL小鼠的寄生虫进行比较来确定。还将通过研究昆虫中PBAQP的表达以及PBAQP破坏对蚊子中PBAQP的影响以及蚊子中PBAQP的影响以及从蚊子传播中的PBAQP的影响来评估疟疾的小鼠模型。到鼠标。目标IV。对人类疟原虫的调查,恶性疟原虫,对于理解水甘露糖蛋白在人类疟疾感染中的作用至关重要。人RBC将被PFAQP null或Wildtype P. falciparum感染,并且比较寄生虫血症。为了确定人RBC水母甘露糖蛋白在疟疾中的作用,将将野生型RBC的寄生虫与AQP3 null RBC进行比较。疟疾是许多欠发达国家疾病和儿童死亡的主要原因。导致疟疾的寄生虫侵入红细胞并繁殖,从而造成巨大的细胞破坏。该应用的目的是定义红细胞和疟疾寄生虫吸收营养甘油的途径,希望这可以揭示用于预防或治疗疟疾的新途径。
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)
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Peter C Agre其他文献
Aquaporin‐Wasserkanäle (Nobel‐Vortrag)
- DOI:
10.1002/ange.200460804 - 发表时间:
2004-08 - 期刊:
- 影响因子:0
- 作者:
Peter C Agre - 通讯作者:
Peter C Agre
Peter C Agre的其他文献
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{{ truncateString('Peter C Agre', 18)}}的其他基金
Malaria Transmission and the Impact of Control Efforts in Southern Africa
南部非洲疟疾传播和控制工作的影响
- 批准号:
8689887 - 财政年份:2010
- 资助金额:
$ 15.84万 - 项目类别:
Malaria Transmission and the Impact of Control Efforts in Southern Africa
南部非洲疟疾传播和控制工作的影响
- 批准号:
8102017 - 财政年份:2010
- 资助金额:
$ 15.84万 - 项目类别:
Malaria Transmission and the Impact of Control Efforts in Southern Africa
南部非洲疟疾传播和控制工作的影响
- 批准号:
8503396 - 财政年份:2010
- 资助金额:
$ 15.84万 - 项目类别:
Malaria Transmission and the Impact of Control Efforts in Southern Africa
南部非洲疟疾传播和控制工作的影响
- 批准号:
7945751 - 财政年份:2010
- 资助金额:
$ 15.84万 - 项目类别:
Malaria Transmission and the Impact of Control Efforts in Southern Africa
南部非洲疟疾传播和控制工作的影响
- 批准号:
9109159 - 财政年份:2010
- 资助金额:
$ 15.84万 - 项目类别:
Malaria Transmission and the Impact of Control Efforts in Southern Africa
南部非洲疟疾传播和控制工作的影响
- 批准号:
8299636 - 财政年份:2010
- 资助金额:
$ 15.84万 - 项目类别:
Regulation, Structure and Function of Aquaporin-6
Aquaporin-6 的调控、结构和功能
- 批准号:
7092996 - 财政年份:2004
- 资助金额:
$ 15.84万 - 项目类别:
Regulation, Structure and Function of Aquaporin-6
Aquaporin-6 的调控、结构和功能
- 批准号:
7459890 - 财政年份:2004
- 资助金额:
$ 15.84万 - 项目类别:
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