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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IDENTIFICATION OF HAPTOGLOBIN AS A NATURAL INHIBITOR OF TRYPANOCIDAL ACTIVITY IN HUMAN SERUM
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IDENTIFICATION OF HAPTOGLOBIN AS A NATURAL INHIBITOR OF TRYPANOCIDAL ACTIVITY IN HUMAN SERUM

机译：鉴定肝糖素是人血清中环戊二酸活性的天然抑制剂

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摘要

Trypanosomes are protozoan parasites of medical and veterinary importance. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense infect humans, causing African sleeping sickness. However, Trypanosoma brucei brucei can only infect animals, causing the disease Nagana in cattle, Man is protected from this subspecies of trypanosomes by a toxic subtype of high density lipoproteins (HDLs) called the trypanosome lytic factor (TLF). The toxic molecule in TLF is believed to be the haptoglobin-related protein that when bound to hemoglobin kills the trypanosome via oxidative damage initiated by its peroxidase activity, The amount of lytic activity in serum varies widely between different individuals with up to a 60-fold difference in activity, In addition, an increase in the total amount of lytic activity occurs during the purification of TLF, suggesting that an inhibitor of TLF (I-TLF) exists in human serum, We now show that the individual variation in trypanosome lytic activity in serum correlates to variations in the amount of I-TLF. Immunoblots of I-TLF probed with antiserum against haptoglobin recognize a 120-kDa protein, indicating that haptoglobin is present in partially purified I-TLF. Haptoglobin involvement is further shown in that it inhibits TLF in a manner similar to I-TLF. Using an anti-haptoglobin column to remove haptoglobin from I-TLF, we show that the loss of haptoglobin coincides with the loss of inhibitor activity. Addition of purified haptoglobin restores inhibitor activity. This indicates that haptoglobin is the molecule responsible for inhibition and therefore causing the individual variation in serum lytic activity. [References: 30]
机译：锥虫是具有医学和兽医学重要性的原生动物寄生虫。布氏锥虫罗氏锥虫和布氏锥虫锥虫感染人类，引起非洲昏睡病。但是，布鲁氏锥虫布鲁氏菌只能感染动物，在牛中引起长Na病。人类被称为锥虫溶解因子（TLF）的高密度脂蛋白（HDL）有毒亚型保护，免受锥虫亚种的侵害。 TLF中的有毒分子被认为是与触珠蛋白有关的蛋白，当与血红蛋白结合时，它会因过氧化物酶活性引发的氧化损伤而杀死锥虫。不同个体之间血清中的裂解活性差异很大，最高可达60倍。活性差异，此外，在纯化TLF的过程中发生了溶解活性总量的增加，表明人血清中存在TLF抑制剂（I-TLF），我们现在证明锥虫溶解活性的个体差异血清中的血浆与I-TLF量的变化相关。用抗触珠蛋白的抗血清探测的I-TLF的免疫印迹可以识别120 kDa的蛋白质，表明触珠蛋白存在于部分纯化的I-TLF中。进一步显示出结合珠蛋白的参与，因为它以类似于I-TLF的方式抑制TLF。使用抗触珠蛋白柱从I-TLF中除去触珠蛋白，我们证明触珠蛋白的损失与抑制剂活性的损失相吻合。添加纯化的触珠蛋白可恢复抑制剂活性。这表明触珠蛋白是负责抑制的分子，因此会引起血清裂解活性的个体变化。 [参考：30]

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