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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.疟疾感染的红细胞的溶血短杆菌肽DH 1-10 μ M短杆菌肽对伯氏疟原虫和恶性疟原虫感染的红细胞的溶血作用以剂量-反应方式迅速发生。与此相反，用10 μ M短杆菌肽处理的异常红细胞的溶血没有被抑制.短杆菌肽D对伯氏疟原虫体内生长的影响感染率约为30%的伯氏疟原虫感染小鼠，在感染的第5 ~ 9天每天腹腔注射短杆菌肽D，或在感染的第0 ~ 3天同时腹腔注射短杆菌肽D，治疗效果显著.渗透保护和形态学观察加入聚乙二醇4，000可保护短杆菌肽D诱导的溶血。这表明短杆菌肽D可以在疟疾感染的红细胞上产生更大的孔，并且所产生的孔的大小可以至少大于37 A。显然，感染的RBC从胞质溶胶中丢失血红蛋白，这与未感染的RBC不同。此外，还观察到从红细胞中逃逸的滋养体、配子体和配子母细胞等游离的寄生虫。然而，不幸的是，电子显微镜没有检测到感染红细胞膜上的任何“洞”。短杆菌肽对恶性疟原虫的影响0.5-1 μ M短杆菌肽处理在体外强烈抑制恶性疟原虫的无性生长。在粘附于黑色素瘤细胞表面的恶性疟原虫感染的红细胞中，这些红细胞被破坏或从黑色素瘤细胞中释放出来，这表明有可能用于治疗严重的疟疾。短杆菌肽DA作用机制的研究用短杆菌肽偶联的环氧活化Sepharose 6 B凝胶柱，从伯氏疟原虫感染红细胞中分离得到一个分子量约为30 kd的单蛋白，该蛋白的分子生物学性质正在研究中。