Microtubules are damaged by diethylcarbamazine, anti-filarial drug

抗丝虫药二乙基卡马嗪会损害微管

• 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

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等人（1983）最近报道了一种培养系统，该系统可使帕杭丝虫的感染性幼虫发育至第四期。我们用Mak的技术进行了初步研究，结果表明，乙胺嗪（DEC）对B幼虫无致死作用。pahangi在体外，即使在高浓度（1毫克/毫升），但它抑制幼虫的生长和发育。这一结果促使我们研究DEC对饲养细胞和丝虫幼虫的影响。本实验所用细胞为LLC-MK_2细胞。DEC抑制这些细胞的增殖，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体。免疫荧光显微镜显示，暴露于DEC的细胞没有细胞质微管复合物的精致图案。随后，研究了DEC对微管的影响。 ...更多信息 用猪脑制备的微管蛋白进行研究。DEC在体外抑制微管的组装和分解预形成的微管。当重新组装或拆卸的产品进行了检查，在DEC的存在下，通过电子显微镜，经常观察到带状微管。这些结果表明DEC破坏了支持丝虫幼虫体外发育的饲养细胞的功能。第二，初步研究了DEC对微丝微管的影响。将感染的幼虫在无饲养细胞的条件下用DEC体外预孵育，然后接种沙鼠。在给定的时间间隔对动物进行尸检，并检查回收的幼虫的发育情况。暴露于DEC的幼虫不能存活很长时间，也不能发育。DEC在体外对幼虫有直接作用，但DEC是否对丝虫蠕虫组织中富含微管的特殊器官--端片体、分泌细胞和分泌细胞有损伤作用尚待解决。少

项目成果

Fujimaki,Y.;Shimada,M.;Kimura,E.;Aoki,Y.: Parasitology Research. 74. 299-300 (1988)

Fujimaki，Y.；Shimada，M.；Kimura，E.；Aoki，Y.：寄生虫学研究。

Y. Fujimaki;M. Shimada;E. Kimura & Y. Aoki: Parasitology Research. 74. 299-300 (1988)

Y.藤卷；M.