Dodecyltriphenylphosphonium inhibits multiple drug resistance in the yeast Saccharomyces cerevisiae

被引：11
作者：
Knorre, Dmitry A. [1 ,2 ]
Markova, Olga V. [1 ]
Smirnova, Ekaterina A. [1 ]
Karavaeva, Iuliia E. [3 ]
Sokolov, Svyatoslav S. [1 ]
Severin, Fedor F. [1 ,2 ]
机构：
[1] Moscow MV Lomonosov State Univ, Belozerslw Inst Physicochem Biol, Moscow 119992, Russia
[2] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow 119992, Russia
[3] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119992, Russia
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2014年 / 450卷 / 04期
关键词：
Yeast; Multiple drug resistance; Dodecyltriphenylphosphonium; Pdr5; Antifungal drugs; BINDING CASSETTE TRANSPORTER; GENE; DERIVATIVES; CATIONS; SEARCH; EFFLUX; PDR5P;
D O I：
10.1016/j.bbrc.2014.07.017
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Multiple drug resistance pumps are potential drug targets. Here we asked whether the lipophilic cation dodecyltriphenylphosphonium (C12TPP) can interfere with their functioning. First, we found that suppression of ABC transporter gene PDR5 increases the toxicity of C12TPP in yeast. Second, C12TPP appeared to prevent the efflux of rhodamine 6G - a fluorescent substrate of Pdr5p. Moreover, C12TPP increased the cytostatic effects of some other known Pdr5p substrates. The chemical nature of C12TPP suggests that after Pdr5p-driven extrusion the molecules return to the plasma membrane and then into the cytosol, thus effectively competing with other substrates of the pump. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码：1481 / 1484
页数：4
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