Functional expression of a multidrug P-glycoprotein transporter of Leishmania
Functional expression of a multidrug P-glycoprotein transporter of Leishmania
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DOI：
10.1016/j.bbrc.2005.02.009
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发表时间：
2005-04-08
影响因子：
3.1
通讯作者：
Castanys, S
中科院分区：
文献类型：
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作者：
Cortés-Selva, F;Muñoz-Martínez, F;Castanys, S
P-糖蛋白（Pap）转运蛋白在真核细胞和原虫如利什曼原虫的多药耐药中起着重要作用。为了寻找新的热带利什曼原虫Pgp逆转剂，我们开发了一种使用杆状病毒-昆虫细胞表达系统的筛选方法。我们证明了MgATP依赖性，钒酸盐敏感的Hoechst 33342在表达Pgp的Sf 9昆虫细胞的膜制备物中的转运。我们已经发现，二氢-β-沉香呋喃倍半萜从美登木cuzcoina抑制Hoechst 33342的运输，与他们的逆转作用在一个多药耐药L。高表达Pgp的热带品系。结果表明，Sf 9细胞膜Hoechst 33342转运系统是一个有效的工具，检查利什曼原虫Pgp与药物的相互作用。(c)2005年爱思唯尔公司All rights reserved.
P-glycoprotein (Pap) transporters play an important role in multidrug resistance in eukaryotic cells and in protozoan parasites such as Leishmania. To search for new reversal agents of the Leishmania tropica Pgp, we developed a screening assay using the Baculovirus-insect cell expression system. We demonstrated a MgATP-dependent, vanadate-sensitive transport of Hoechst 33342 in membrane preparations of Sf9 insect cells expressing Pgp. We have found that dihydro-beta-agarofuran sesquiterpenes from Maytenus cuzcoina inhibited Hoechst 33342 transport that correlates with their reversal effect in a multidrug-resistant L. tropica line over-expressing Pgp. The results suggest that Sf9 cell membrane Hoechst 33342 transport system represents an efficient tool for examining the interactions of Leishmania Pgp with pharmacological agents. (c) 2005 Elsevier Inc. All rights reserved.