Microtubules are damaged by diethylcarbamazine, anti-filarial drug

抗丝虫药二乙基卡马嗪会损害微管

基本信息

批准号：
62570178
负责人：
AOKI Yoshiki
金额：
$ 1.09万
依托单位：
Institute of Tropical Medicine, Nagasaki Niversity
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570178/
关键词：
Filarial worm Diethlcarbamazine 微小管糸状虫

项目摘要

Mak et al. (1983) recently reported an culture system that allows the infective larvae of Brugia pahangi to develop to the fourth stage. Our preliminary study by using the technique of Mak suggested that diethylcarbamazine (DEC) does not kill the larvae of B. pahangi in vitro, even at a high concentration (1 mg/ml), but it inhibits the growth and development of larvae. This results encouraged us to examine the effect of DEC on the feeder cells and filarial larvae.Firstly the effect of DEC on the feeder cells was studied. The cells used in our study were LLC-MK_2 cells. DEC inhibited proliferation of these cells, and cells grown in the presence of DEC were likely to separate from each other and became round in shape. These results encouraged us to study the cytoplasmic microtubules complex. Immunofluorescence microscopy revealed that the cells exposed to DEC were devoid of the delicate pattern of the cytoplasmic microtubules complex. Subsequently, the effect of DEC on microtubules was s … More tudied by using microtubule protein prepared from porcine brain. DEC inhibited assembly of microtubules and disassembled preformed microtubules in vitro. When the reassembled or disassembled products were examined in the presence of DEC by electron microscopy; ribbon-microtubules were frequently observed. These results strongly suggest that DEC disrupts the function of the feeder cells which support the development of filarial larvae in vitro.Secondly, a preliminary study was designed to know the effect of DEC on filasial microtubules. The infective larvae were pre-incubated with DEC in vitro in the absence of feede cells and then inoculated into jirds. The animals were necropsied at a given intervals and the larvae recovered were examined for development. The larvae exposed to DEC did not survive long, nor develop. As we know that DEC has direct effect on larvae in vitro, the problem to be solved is whether DEC gives any damage on amphids, phasmids and excretory cells, the specific organs which are rich in microtubules among the organs and tissues of filarial worms. Less

Mak等。（1983年）最近报道了一种培养系统，该系统使Brugia Pahangi的感染性幼虫发展到第四阶段。我们通过使用MAK技术的初步研究表明，即使在高浓度（1 mg/ml）的情况下，二乙基卡马嗪（DEC）也不会在体外杀死B. pahangi的幼虫，但它抑制了幼虫的生长和发育。该结果鼓励我们检查DEC对馈线细胞和丝状幼虫的影响。首先研究了DEC对馈线细胞的影响。我们研究中使用的细胞是LLC-MK_2细胞。 DEC抑制了这些细胞的增殖，并且在DEC存在下生长的细胞可能彼此分离并变成圆形。这些结果鼓励我们研究细胞质微管复合物。免疫荧光显微镜表明，暴露于DEC的细胞没有细胞质微管复合物的微妙模式。随后，通过使用由猪脑制备的微管蛋白来更加研究DEC对微管的影响。 DEC在体外抑制了微管和拆卸的预制微管的组装。当通过电子显微镜在DEC的存在下检查重新组装或拆卸的产物时；经常观察到色带微管。这些结果强烈表明，DEC破坏了支持丝状幼虫在体外发展的馈线功能。首先，初步研究旨在了解DEC对毛囊微管的影响。在没有饲料细胞的情况下，将感染性幼虫与DEC预孵育，然后接种成jird。将这些动物在给定的时间间隔内被致命，并检查了回收的幼虫进行发育。暴露于DEC的幼虫生存很长，也没有发育。众所周知，DEC对体外的幼虫有直接的影响，要解决的问题是DEC是否会对丝状战争器官和组织中富含微管的特定器官造成任何损害。较少的