权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

ANALYSES OF MECHANISMS FOR PLASMODIUM ADAPTATION TO THE HOST ERYTHROCYTES

疟原虫对宿主红细胞的适应机制分析

基本信息

批准号：
61570197
负责人：
TANABE Kazuyuki
金额：
$ 1.66万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570197/
关键词：
MALARIA PARASITES PLASMODIUM ERYTHROCYTES PARASITIC ADAPTATION GLUCOSE GENE クローニングプラスモティウム

项目摘要

To obtain fundamental knowledge necessary for developing malaria vaccines and new antimalarials, mechanisms for adaptation by malaria parasites to their host erythrocytes have been studied at the molecular and cellular levels. Results are as follows:I. Membrane transport of metabolites in malaria-infected cells. (1) Plasmodium falciparum grows well in human erythrocytes, whose potassium levels ae reduced greatly by treatment with ouabain. (2) An appearance of small pores in the membranes of P. yoelii-infected cells lead to increase in the uptake of 2-deoxy-D-glucose. An electrical potential of protons across the plasma membrane of intraerythrocytic parasites is coupled to an uphill active uptake of 2-deoxy-D-glucose. (3) The mitochondrion of P. yoelii has an inside negative membrane potential.II. Polymorphism of a surface antigen of P. falciparum merozoite. (1) The gene for a precursor (p190) to major merozoite surface antigens of P. falciparum has been cloned and sequenced. Comparisons of the p190 gene from several parasite isolates has revealed both conserved and variable regions. (2) Variations in the sequence are not widely polymorphic but fall into two types. Southern blot analyses of genomic DNA from 14 isolates has shown that the p190 gene is dimorphic alles. it is suggested that intragenic recombination of the p190 alles creates the antigen's polymorphism.III. Calcium metabolism of malaria-infected erythrocytes. (1) Disturbance of calcium metabolism of P. yoelii- and P. falciparum-infected cells by Ca^<2+> ionophore, calcium antagonists and calmodulin inhibitors results in the death of the parasites.

为了获得开发疟疾疫苗和新抗疟药所需的基本知识，在分子和细胞水平上研究了疟原虫对其宿主红细胞的适应机制。结果如下：I.疟疾感染细胞代谢物的膜转运。(1)恶性疟原虫在人红细胞中生长良好，而用哇巴因处理后，红细胞中的钾水平大大降低。(2)约氏疟原虫感染的细胞膜中出现小孔，导致2-脱氧-D-葡萄糖摄取增加。质子穿过红细胞内寄生虫的质膜的电势与2-脱氧-D-葡萄糖的上坡主动摄取耦合。(3)约氏疟原虫的胞浆内具有负膜电位。恶性疟原虫裂殖子表面抗原的多态性。(1)恶性疟原虫主要裂殖子表面抗原的前体基因（p190）已被克隆和测序。从几个寄生虫分离株的p190基因的比较，揭示了保守和可变区。(2)序列中的变异不是广泛多态的，而是分为两种类型。对14个分离株基因组DNA的Southern杂交分析表明，p190基因为二型等位基因。提示p190等位基因的基因内重组产生了抗原的多态性。疟疾感染红细胞的钙代谢。(1)约氏疟原虫和恶性疟原虫感染细胞的钙代谢被Ca^2+载体、钙拮抗剂和钙调素抑制剂干扰，导致疟原虫死亡。