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Dynamin like protein 1 participated in the hemoglobin uptake pathway of Plasmodium falciparum
  • ISSN号:0366-6999
  • 期刊名称:《中华医学杂志:英文版》
  • 时间:0
  • 分类:Q51[生物学—生物化学] S858.315.9[农业科学—临床兽医学;农业科学—兽医学;农业科学—畜牧兽医]
  • 作者机构:[1]Department of Microbiology and Parasitology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5# Dong Dan San Tiao, Rm. 522, Beijing 100005, China
  • 相关基金:This work was supported by the research grants from the National Basic Research Program of China (973 Program, No. 2007CB513100), the High-Tech Research and Development Program of China (863 Program, No. 2006AA028471), the China's Major Infectious Diseases of Major Special Program (No. 2008ZX10004-011), and the grant of National Natural Science Foundation of China (No. 30170876).
中文摘要:

背景在疟疾感染的血阶段期间,寄生虫在宿主红血细胞使内在化并且降级为他们的发展的血红素的巨大的数量。尽管寄生虫的血红素举起小径的形态学清楚地被观察了,很少对它的分子的机制被知道了。方法从变形体 falciparum 的 recombinant 蛋白质,象蛋白质 1 一样的 dynamin (PfDYN1 ) 并且 2 (PfDYN2 ) GTPase 领域,在 E .coli 被表示并且显示出 GTPase 活动。由使用一个 dynamin 禁止者, dynasore,我们在血红素举起小径表明了 PfDYN1 的参与。结果二 recombinant 蛋白质的 GTPase 活动被 dynasore 在 vitro 禁止。有在戒指和早 trophozoite 舞台的 80 mol/L dynasore 的寄生虫文化的处理导致了寄生虫生长的实质的抑制并且在血红素量的明显的衰落。而且,减少了 intraceliular hemozoin 累积和 FITC 葡聚糖的减少的举起也被观察,和在在 dynasore 处理以后的寄生虫的超微结构的特殊变化。我们的结果看那 PfDYN1 的结论在 P 的血红素举起小径起一个重要作用。Falciparum 并且建议它是为疟疾化疗的一个新奇目标的可能性。

英文摘要:

Background During the blood stage of malaria infection, parasites internalize in the host red blood cells and degrade massive amounts of hemoglobin for their development. Although the morphology of the parasite's hemoglobin uptake pathway has been clearly observed, little has been known about its molecular mechanisms. Methods The recombinant proteins from Plasmodium falciparum, dynamin like protein 1 (PfDYN1) and 2 (PfDYN2) GTPase domain, were expressed in E .coil and showed GTPase activity. By using a dynamin inhibitor, dynasore, we demonstrated the involvement of PfDYN1 in the hemoglobin uptake pathway. Results The GTPase activity of the two recombinant proteins was inhibited by dynasore in vitro. Treatment of parasite cultures with 80 μmol/L dynasore at the ring and early trophozoite stage resulted in substantial inhibition of parasite growth and in an obvious decline of hemoglobin quantum. Furthermore, reduced intracellular hemozoin accumulation and decreased uptake of the FITC-dextran were also observed, together with distinctive changes in the ultrastructure of parasites after the dynasore treatment. Conclusions Our results show that PfDYN1 plays an important role in the hemoglobin uptake pathway of P. falciparum and suggest its possibility of being a novel target for malaria chemotherapy.

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期刊信息
  • 《中华医学杂志:英文版》
  • 中国科技核心期刊
  • 主管单位:中国科协
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京东四西大街四十二号
  • 邮编:100710
  • 邮箱:cmj@cma.org.cn
  • 电话:010-85158321
  • 国际标准刊号:ISSN:0366-6999
  • 国内统一刊号:ISSN:11-2154/R
  • 邮发代号:2-920
  • 获奖情况:
  • 1997、1998、1999年获中国科协优秀科技期刊择优资...,1992、1997年连续两年荣获全国优秀科技期刊和中国...,中国期刊方阵双高期刊
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  • 被引量:3319