Studies on anti-malarial activity of gramicidin

短杆菌肽抗疟活性研究

基本信息

批准号：
04670227
负责人：
KAWAMOTO Fumihiko
金额：
$ 1.41万
依托单位：
Nagoya 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：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

1. Hemolysis of malaria-infected erythrocytes gramicidin DHemolysis of P.berghei- and P.falciparum-infected erythrocytes by 1-10 muM gramicidin quickly occurred in a dose-response manner. On the contrary, hemolysis of Anormal erythrocytes treated with 10 muM gramicidin was not observed.2. Effects of gramicidin D on the growth of P.berghei in vivo.When infected mice with about 30% parasitaemia were administrated gramicidin D by daily injections into the peritoneal cavity from day 5 to day 9, or given intraperitoneal administration from day 0 to day 3 at the same time of infection, remarkable effectiveness for cure was observed.3. Osmotic protection and morphological observationThe gramicidin D-induced hemolysis was protected by addition of polyethyleneglycol 4,000. This indicates that gramicidin D may produce bigger pore on the malaria-infected erythrocytes, and that the pore size produced may be, at least, bigger than 37A.It was apparent that the infected RBC lost hemoglobins from the cytosol, differing from non-infected RBCs. In addition, free prasites including trophozoites, schizonts and gametocytes escaped from RBCs were also seen. Unfortunately, however, any 'hole' on the membrane of the infected RBCs was not detected by electronmicroscopy.4. Effects of gramicidin on P.falciparumTreatment with 0.5-1 muM gramicidin strongly inhibited the asexual growth of P.falciparum in vitro. In P.falciparum-infected RBCs adhering to the surface of melanoma cells, these RBCs were broken or released from melanoma cells, indicating a possibility to use cure for severe malaria.5. Investigation on the action mechanism of gramicidin DA single protein of about 30kd was isolated from the p. berghei-infected erythrocytes by the batch method using gramicidin-conjugated Epoxy-activated Sepharose 6B.Molecular and biochemical properties of this protein is now being investigated.

1。疟疾的红细胞的溶血对P. berghei-和P. falciparum感染的红细胞的溶血素溶解1-10 mum gramicidin迅速以剂量反应方式发生。相反，未观察到用10 mum cramicidin治疗的非正常红细胞溶血。2。 Gramicidin D对体内P.berghei生长的影响。当感染约30％寄生虫血症的小鼠是通过每天从第5天到第9天给予腹膜腔的每天给腹膜腔的施用，或从第3天给予腹膜内给药。在感染的同时，观察到了明显的治愈有效性。3。渗透保护和形态学观察结果通过添加聚乙二醇4,000来保护gramicidin d诱导的溶血。这表明谷霉素D可能会在疟疾感染的红细胞上产生更大的毛孔，并且产生的孔径至少可能大于37a。显然，被感染的RBC丢失的RBC丢失的血红蛋白与未感染的细胞质有所不同RBCS。此外，还看到了从RBC逃脱的滋养体，精元和配子细胞在内的自由原始人。但是，不幸的是，没有通过电子显微镜检测到感染RBC的膜上的任何“孔”。4。 Gramicidin对0.5-1妈妈gramicidin对falciparumtreatment的影响强烈抑制了falciparum p.falciparum的无性生长。在粘附在黑色素瘤细胞表面的falciparum P. falciparum的RBC中，这些RBC被破坏或从黑色素瘤细胞中释放出来，表明有可能将治愈方法用于严重疟疾。5。从p中分离出gramicidin dA单蛋白的作用机理的研究。使用谷霉素偶联的环氧激活的Sepharose 6B通过批处理方法感染了贝尔格人的红细胞。该蛋白的分子和生化特性现在正在研究中。