Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse model.
Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse model.
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DOI：
10.1084/jem.20071463
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发表时间：
2008-08-04
期刊：
影响因子：
--
通讯作者：
Raper J
中科院分区：
文献类型：
--
作者：
Molina-Portela MP;Samanovic M;Raper J
人类表达一种独特的高密度脂蛋白（HDL）亚类，称为锥虫裂解因子（TLF），可杀死许多锥虫属寄生虫物种。本研究通过转基因的方法在小鼠体内表达了与TLF结构和功能相关的载脂蛋白（apo）A-I、apoL-I和触珠蛋白相关蛋白，以探讨它们在体内的生理作用。转基因表达的人载脂蛋白L-I单独赋予锥虫溶解活性在体内。人载脂蛋白A-I和触珠蛋白相关蛋白（Hpr）的共表达对载脂蛋白L-I整合到HDL中有影响，并且这两种蛋白都需要增加TLF的比活性，这是体外可测量的。出乎意料的是，截短的载脂蛋白L-I缺乏血清抗性基因相互作用域，这是以前显示杀死人类感染性锥虫，是不是锥虫在转基因小鼠，尽管与人载脂蛋白A-I和Hpr共表达，并纳入HDL。我们的结论是，所有三个人载脂蛋白合作，以达到最大的杀伤能力，截短的载脂蛋白L-I在转基因动物中不起作用。
Humans express a unique subset of high-density lipoproteins (HDLs) called trypanosome lytic factors (TLFs) that kill many Trypanosoma parasite species. The proteins apolipoprotein (apo) A-I, apoL-I, and haptoglobin-related protein, which are involved in TLF structure and function, were expressed through the introduction of transgenes in mice to explore their physiological roles in vivo. Transgenic expression of human apolipoprotein L-I alone conferred trypanolytic activity in vivo. Coexpression of human apolipoprotein A-I and haptoglobin-related protein (Hpr) had an effect on the integration of apolipoprotein L-I into HDL, and both proteins were required to increase the specific activity of TLF, which was measurable in vitro. Unexpectedly, truncated apolipoprotein L-I devoid of the serum resistance gene interacting domain, which was previously shown to kill human infective trypanosomes, was not trypanolytic in transgenic mice despite being coexpressed with human apolipoprotein A-I and Hpr and incorporated into HDLs. We conclude that all three human apolipoproteins act cooperatively to achieve maximal killing capacity and that truncated apolipoprotein L-I does not function in transgenic animals.
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影响因子：
4.8
作者：
Muranjan, M;Nussenzweig, V;Tomlinson, S
通讯作者：
Tomlinson, S
影响因子：
2.2
作者：
Shiflett, April M.;Faulkner, Sara D.;Hajduk, Stephen L.
通讯作者：
Hajduk, Stephen L.
影响因子：
1.5
作者：
TOMLINSON, S;JANSEN, AM;NUSSENZWEIG, V
通讯作者：
NUSSENZWEIG, V
DOI：
10.1073/pnas.0609902104
发表时间：
2007-03-06
影响因子：
11.1
作者：
Vanhollebeke, Benoit;Nielsen, Marianne J.;Pays, Etienne
通讯作者：
Pays, Etienne
影响因子：
158.5
作者：
Vanhollebeke, Benoit;Truc, Philippe;Pays, Etienne
通讯作者：
Pays, Etienne