The role of tegumental aquaporin from the human parasitic worm, Schistosoma mansoni, in osmoregulation and drug uptake
The role of tegumental aquaporin from the human parasitic worm, Schistosoma mansoni, in osmoregulation and drug uptake
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DOI：
10.1096/fj.09-130757
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发表时间：
2009-08-01
期刊：
影响因子：
4.8
通讯作者：
Skelly, Patrick J.
中科院分区：
文献类型：
--
作者：
Faghiri, Zahra;Skelly, Patrick J.
血吸虫是寄生扁形动物，构成全球重要的公共卫生问题。感染的特征是在宿主的脉管系统中存在成虫，它们可以在那里生存多年。这些蠕虫被一种不寻常的双层脂质双层覆盖，通过它输入营养物质。寄生虫如何输入其他重要分子（例如水）尚不清楚。最近对血吸虫皮膜的蛋白质组学分析揭示了在宿主相互作用表面存在水通道蛋白同源物，我们已经克隆并表征了其 cDNA。该 cDNA 编码预测的 304 个氨基酸蛋白 (SmAQP)，通过免疫定位，该蛋白主要存在于寄生虫外皮中，并且在血管内生命阶段表达最高。用针对 SmAQP 基因的短干扰 RNA 治疗寄生虫可产生有效的 (>90%) 抑制。这些被抑制的寄生虫在置于低渗介质中时可以抵抗肿胀，这与对照寄生虫不同，对照寄生虫的体积迅速翻倍。此外，与对照不同，SmAQP 抑制的寄生虫在高渗溶液中孵育时可抵抗收缩。虽然与对照组相比，被抑制的寄生虫在培养物中表现出较低的生存能力，并且在长期抑制后表现出发育不良的外观，但它们对药物酒石酸锑钾 (PAT) 的杀灭能力更强。这可能是因为 SmAQP 充当该药物的导管，就像其他系统中的水通道蛋白的情况一样。这些实验揭示了血吸虫外皮在控制水和药物进入寄生虫中的迄今为止未被认识的作用，并强调了外皮在寄生虫渗透压调节和药物摄取中的重要性。-Faghiri, Z., Skelly, P. J. 来自人类寄生虫曼氏血吸虫的外皮水通道蛋白在渗透压调节和药物摄取中的作用。 FASEB J. 23, 2780-2789 (2009)
Schistosomes are parasitic platyhelminths that constitute an important public health problem globally. Infection is characterized by the presence of adult worms within the vasculature of their hosts, where they can reside for many years. The worms are covered by an unusual dual lipid bilayer through which they import nutrients. How the parasites import other vital molecules, such as water, is not known. Recent proteomic analysis of the schistosome tegumental membranes revealed the presence of an aquaporin homologue at the host-interactive surface whose cDNA we have cloned and characterized. The cDNA encodes a predicted 304-aa protein (SmAQP) that is found largely in the parasite tegument by immunolocalization and is most highly expressed in the intravascular life stages. Treatment of parasites with short interfering RNAs targeting the SmAQP gene results in potent (>90%) suppression. These suppressed parasites resist swelling when placed in hypotonic medium, unlike their control counterparts, which rapidly double in volume. In addition, SmAQP-suppressed parasites, unlike controls, resist shrinkage when incubated in hyperosmotic solution. While suppressed parasites exhibit lower viability in culture relative to controls and exhibit a stunted appearance following prolonged suppression, they are nonetheless more resistant to killing by the drug potassium antimonyl tartrate (PAT). This is likely because SmAQP acts as a conduit for this drug, as is the case for aquaporins in other systems. These experiments reveal a heretofore unrecognized role of the schistosome tegument in controlling water and drug movement into the parasites and highlight the importance of the tegument in parasite osmoregulation and drug uptake.-Faghiri, Z., Skelly, P. J. The role of tegumental aquaporin from the human parasitic worm, Schistosoma mansoni, in osmoregulation and drug uptake. FASEB J. 23, 2780-2789 ( 2009)