Antonenko Yuri N, Rokitskaya Tatyana I, Huczyński Adam
A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia.
A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia.
Biochim Biophys Acta. 2015 Apr;1848(4):995-1004. doi: 10.1016/j.bbamem.2015.01.005. Epub 2015 Jan 17.
Monensin is a carrier of cations through lipid membranes capable of exchanging sodium (potassium) cations for protons by an electroneutral mechanism, whereas its ethyl ester derivative ethyl-monensin is supposed to transport sodium (potassium) cations in an electrogenic manner. To elucidate mechanistic details of the ionophoric activity, ion fluxes mediated by monensin and ethyl-monensin were measured on planar bilayer lipid membranes, liposomes, and mitochondria. In particular, generation of membrane potential on liposomes was studied via the measurements of rhodamine 6G uptake by fluorescence correlation spectroscopy. In mitochondria, swelling experiments were expounded by the additional measurements of respiration, membrane potential, and matrix pH. It can be concluded that both monensin and ethyl-monensin can perform nonelectrogenic exchange of potassium (sodium) ions for protons and serve as electrogenic potassium ion carriers similar to valinomycin. The results obtained are in line with the predictions based on the crystal structures of the monensin complexes with sodium ions and protons (Huczyński et al., Biochim. Biophys. Acta, 1818 (2012) pp. 2108-2119). The functional activity observed for artificial membranes and mitochondria can be applied to explain the activity of ionophores in living systems. It can also be important for studying the antitumor activity of monensin.
莫能菌素是一种通过脂质膜的阳离子载体，能够通过电中性机制将钠（钾）阳离子与质子进行交换，而其乙酯衍生物乙基莫能菌素则被认为是以生电方式转运钠（钾）阳离子。为了阐明离子载体活性的机制细节，在平面双层脂质膜、脂质体和线粒体上测量了莫能菌素和乙基莫能菌素介导的离子通量。特别地，通过荧光相关光谱法测量罗丹明6G摄取来研究脂质体上膜电位的产生。在线粒体中，通过额外测量呼吸作用、膜电位和基质pH来阐述肿胀实验。可以得出结论，莫能菌素和乙基莫能菌素都可以进行钾（钠）离子与质子的非生电交换，并作为类似于缬氨霉素的生电钾离子载体。所获得的结果与基于莫能菌素与钠离子和质子的晶体结构的预测一致（胡钦斯基等人，《生物化学与生物物理学报》，1818（2012年），第2108 - 2119页）。在人工膜和线粒体中观察到的功能活性可用于解释离子载体在生命系统中的活性。这对于研究莫能菌素的抗肿瘤活性也可能很重要。
