阿尔特米西宁向的是Plasmodium falciparum病毒的SERCA
U Eckstein-Ludwig1, R J Webb, I D A Van Goethem
1Department of Cellular and Molecular Medicine, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
Nature
|August 22, 2003
概括
强效的抗疟疾药物阿尔特米西宁向的是Plasmodium falciparum SERCA (PfATP6) 的正确基因. 铁激活了艺术素,导致pfATP6抑制和寄生虫在食物真空外死亡.
科学领域:
- 寄生虫学的寄生虫学
- 药用化学 医学化学
- 分子生物学分子生物学
背景情况:
- 阿尔特米西宁是对抗多药耐药疟疾的关键抗疟药物.
- 它们的精确分子标仍然难以捉摸,尽管广泛使用.
- 阿尔特米西宁是从甜蜜的 (Artemisia annua) 中提取的六甲烯乳.
研究的目的:
- 为了识别Plasmodium falciparum中artemisinins的分子标. 为了确定在Plasmodium falciparum中artemisinins的分子标.
- 为了阐明艺术素的作用和激活的机制.
主要方法:
- 使用表达Plasmodium falciparum SERCA (PfATP6) 的Xenopus卵细胞进行抑制试验.
- 与已知SERCA抑制剂thapsigargin进行对抗性研究.
- 评估脱氧甲美西宁的活性.
- 用desferrioxamine进行铁化实验.
- 寄生虫的光成像用标记的艺术素和thapsigargin.
主要成果:
- 阿尔特米西宁可以抑制PfATP6,其效力相当于thapsigargin.
- 塔普西加尔金对抗阿尔特米西宁的抗疟疾活性.
- 由于缺乏内氧化桥梁,德索西阿特米西宁是无效的.
- 铁化取消了素的抗寄生虫作用和pfATP6抑制.
- 甲素以铁依赖的方式标记寄生虫,局部化到细胞质中.
结论:
- 阿尔特米西宁的作用是通过抑制Plasmodium falciparum的SERCA (PfATP6) 的正源物进行抑制.
- 铁 (Fe2+) 对于素激活至关重要,可能有助于内氧化物桥梁裂变.
- 目标部位位于食物真空体外,观察到细胞溶液局部化.
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