Uncoupling and toxic action of alkyltriphenylphosphonium cations on mitochondria and the bacterium Bacillus subtilis as a function of alkyl chain length
Uncoupling and toxic action of alkyltriphenylphosphonium cations on mitochondria and the bacterium Bacillus subtilis as a function of alkyl chain length
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DOI：
10.1134/s000629791512007x
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发表时间：
2015-12-01
影响因子：
2.8
通讯作者：
Skulachev, V. P.
中科院分区：
文献类型：
--
作者：
Khailova, L. S.;Nazarov, P. A.;Skulachev, V. P.
研究了三苯基膦(C-n-TPP+)的烷基衍生物(C-n-TPP+)在分离的线粒体、细菌和脂质体体系中的渗透性。与罗丹明-19的某些衍生物(酯)相反，其中丁基罗丹明具有最大的活性，而在C-n-TPP的情况下，对线粒体呼吸的刺激作用随着烷基长度的增加而稳步增加。四苯基膦和丁基TPP+在几百微克分子的剂量下表现出解偶联效应，这可能与C-n-TPP+与内源脂肪酸相互作用并诱导其自身的循环转移，导致质子跨线粒体膜运输有关。通过测定C-n-TPP+对脂质体中羧基荧光素外流的影响，探讨了这一机制。细菌实验表明，与苯二酚类似物(SkQ1)的十二烷基TPP+、正十二烷基TPP+和辛基TPP+对革兰氏阳性杆菌枯草芽孢杆菌的生长有抑制作用，且抑制作用随着亲脂性的增强而增强。这些阳离子对革兰氏阴性杆菌的生长没有毒性作用。推测细菌对不同菌种的毒性作用差异可能与菌衣对三苯基膦阳离子的渗透性不同有关。
A series of permeating cations based on alkyl derivatives of triphenylphosphonium (C-n-TPP+) containing linear hydrocarbon chains (butyl, octyl, decyl, and dodecyl) was investigated in systems of isolated mitochondria, bacteria, and liposomes. In contrast to some derivatives (esters) of rhodamine-19, wherein butyl rhodamine possessed the maximum activity, in the case of C-n-TPP a stimulatory effect on mitochondrial respiration steadily increased with growing length of the alkyl radical. Tetraphenylphosphonium and butyl-TPP+ at a dose of several hundred micromoles exhibited an uncoupling effect, which might be related to interaction between C-n-TPP+ and endogenous fatty acids and induction of their own cyclic transfer, resulting in transport of protons across the mitochondrial membrane. Such a mechanism was investigated by measuring efflux of carboxyfluorescein from liposomes influenced by C-n-TPP+. Experiments with bacteria demonstrated that dodecyl-TPP+, decyl-TPP+, and octyl-TPP+ similarly to quinone-containing analog (SkQ1) inhibited growth of the Gram-positive bacterium Bacillus subtilis, wherein the inhibitory effect was upregulated with growing lipophilicity. These cations did not display toxic effect on growth of the Gram-negative bacterium Escherichia coli. It is assumed that the difference in toxic action on various bacterial species might be related to different permeability of bacterial coats for the examined triphenylphosphonium cations.