Overexpression of LaMDR2, a novel multidrug resistance ATP-binding cassette transporter, causes 5-fluorouracil resistance in Leishmania amazonensis
Overexpression of LaMDR2, a novel multidrug resistance ATP-binding cassette transporter, causes 5-fluorouracil resistance in Leishmania amazonensis
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DOI：
10.1016/s0014-5793(04)00130-9
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发表时间：
2004-03-12
期刊：
影响因子：
3.5
通讯作者：
Hashiguchi, Y
中科院分区：
文献类型：
--
作者：
Katakura, K;Fujise, H;Hashiguchi, Y
三磷酸腺苷结合盒(ABC)蛋白在多种生物的耐药和解毒中发挥着重要作用。在这里，我们分离到了亚马逊利什曼原虫ABC蛋白多药耐药(MDR)亚家族的新成员LaMDR2。LaMDR2与其亲缘关系最近的蛋白质LaMDR1的氨基酸同源性为47%，LaMDR1以前是从同一物种中分离出来的。过量表达LaMDR2的原生殖体对5-氟尿嘧啶(5-FU)表现出显著的抗性，但对LaMDR1底物没有明显的抗性。在对数时相细胞中LaMDR2的表达相对较高，而在对数时相细胞中[H-3]5-FU的积聚较低。这些结果表明，LaMDR2参与了外源物质的排出，但在功能上与LaMDR1不同。(C)2004年欧洲生化学会联合会。爱思唯尔出版，版权所有。
The ATP-binding cassette (ABC) proteins play an important role in drug resistance and detoxification in various organisms. Here we isolated LaMDR2, a new member of the multidrug resistance (MDR) subfamily of ABC proteins in Leishmania amazonensis. LaMDR2 exhibited 47% amino acid identity to its most closely related protein, LaMDR1, which was previously isolated from the same species. Promastigotes that overexpressed LaMDR2 showed significant resistance to 5-fluorouracil (5-FU), but not to LaMDR1 substrates. Expression of LaMDR2 in the transfectants was relatively higher in the log phase than the stationary phase, and a lower accumulation of [H-3]5-FU was observed in the log-phase cells. These results suggest that LaMDR2 is involved in extrusion of xenobiotics, but functionally different from LaMDR1. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.