A potential screening factor for accumulation of cholesteyl ester transfer protein deficiency in East Asia: Schistosoma japonicum
A potential screening factor for accumulation of cholesteyl ester transfer protein deficiency in East Asia: Schistosoma japonicum
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东亚地区胆固醇酯转运蛋白缺乏症累积的潜在筛选因素：日本血吸虫
DOI：
10.1016/j.bbalip.2013.12.014
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Yokoyama S.
中科院分区：
文献类型：
--
作者：
城本高志;岡部直彦;陸豊;中村ー丸山恵美;氷見直之;成田和彦;木村和美;宮本修;川島聡・飯野由里子・西倉実季・星加良司;菊地豪，山縣憲司，佐藤和聡，木村健一，山下年晴，大根田修;川越敏司・川島聡・星加良司;Yokoyama S.
胆固醇酯转移蛋白（CETP）缺乏症表现出独特的血浆脂蛋白谱，无其他明显症状。它在东亚非常常见，而在其他地方则相当罕见。因此，一个潜在的环境筛选因素可能有助于这种偏心分布，例如其对区域性疾病的选择性优势，最有可能是感染性疾病，与血浆脂蛋白有关。血吸虫通过脂蛋白受体样系统利用宿主血浆脂蛋白作为营养源。其亚洲特有种日本血吸虫（Schistosoma（S）japonicum）在东亚流行，从高密度脂蛋白（HDL）中摄取胆固醇酯（CE）用于其卵的胚胎发育为毛蚴，这是该寄生虫肝脏发病机制的关键步骤，但缺乏CETP的HDL的情况很差。本研究从日本血吸虫成虫和卵中克隆了CD 36相关蛋白（CD 36 RP）。该基因全长1880 bp，编码506个氨基酸残基，具有CD 36结构域和两个跨膜区。其胞外结构域选择性结合人HDL，但既不LDL也不CETP缺陷HDL，并且针对胞外结构域的抗体抑制选择性HDL-CE摄取和卵的胚胎化。当感染S.日本血吸虫，野生型小鼠发生肝肉芽肿比CETP-转基因小鼠异位卵胚。因此，CD 36 RP是S的候选受体。大豆异黄酮能促进卵胚发育所必需HDL-CE的摄取。由CETP缺乏引起的异常HDL延缓了这一过程，从而保护患者免受肝脏病变的发展。日本血吸虫感染是东亚地区CETP缺乏症高发的潜在筛选因素。
Cholesteryl ester transfer protein (CETP)-deficiency manifests a unique plasma lipoprotein profile without other apparent symptoms. It is highly common in East Asia while rather rare anywhere else. A potential environmental screening factor(s) may therefore contribute to this eccentric distribution, such as its selective advantage against a regional illness, most likely an infectious disease, in relation to plasma lipoproteins. Blood flukes use the host plasma lipoproteins as nutrient sources through the lipoprotein receptor-like systems. Its Asian-specific species,Schistosoma (S) japonicum, which has been endemic in East Asia, takes up cholesteryl ester (CE) from high-density lipoprotein (HDL) for the embryonation of their eggs to miracidia, a critical step of the hepatic pathogenesis of this parasite, but poorly from HDL of CETP-deficiency. CD36-related protein (CD36RP) was cloned from the adults and the eggs ofS. japonicum, with 1880-bp encoding 506 amino-acid residues exhibiting the CD36 domains and two transmembrane regions. Its extracellular domain selectively bound human HDL but neither LDL nor CETP-deficiency HDL, and the antibody against the extracellular domain suppressed the selective HDL-CE uptake and embryonation of the eggs. When infected withS. japonicum, wild-type mice developed less hepatic granulomatosis than CETP-transgenic mice by the ectopic egg embryonation. CD36RP is thus a candidate receptor ofS. japonicumto facilitate uptake of HDL-CE necessary for egg embryonation. Abnormal HDL caused by CETP-deficiency retards this process and thereby protects the patients from development of hepatic lesions.S. japonicuminfection is a potential screening factor for high prevalence of CETP deficiency in East Asia.