Evidence for nystatin micelles in L-cell membranes from fluorescence photobleaching measurements of diffusion.
Evidence for nystatin micelles in L-cell membranes from fluorescence photobleaching measurements of diffusion.
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来自扩散荧光光漂白测量的 L 细胞膜中制霉菌素胶束的证据。
DOI：
10.1021/bi00349a026
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发表时间：
1986
期刊：
影响因子：
2.9
通讯作者：
Petersen,NO
中科院分区：
文献类型：
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作者：
O'Neill,LJ;Miller,JG;Petersen,NO
西安大略大学化学系，伦敦，安大略省，N6A 5B7 加拿大 1985 年 4 月 24 日收到 摘要：发现多烯抗生素制霉菌素的硝基苯并恶二唑衍生物在 L 细胞膜中的扩散取决于膜中制霉菌素的浓度。随着制霉菌素浓度的增加，通过荧光光漂白测量的其扩散系数呈双曲线下降。当衍生物的浓度增加时，会重现这种行为。相反，在这些条件下，磷脂的硝基苯并恶二唑衍生物的扩散对制霉菌素浓度不敏感。如果制霉菌素在膜内以单体-胶束平衡存在，但不能通过结合或相分配来解释，则可以理解制霉菌素特异性扩散变化。^ 制霉菌素是临床上用作抗真菌剂的几种多烯抗生素之一（Hammond，1977；Medoff 等，1983）。已知这些药物是膜活性剂，可诱导酵母、红细胞和哺乳动物细胞（包括鼠 L 细胞）中 K+ 渗漏和细胞裂解（Gale，1974）。大量关于模型膜的工作[由 Hammond (1977) 审查] 得出这样的结论：制霉菌素和两性霉素 B 等多烯抗生素与膜中的甾醇结合形成跨膜孔（de Kruijff & Demel，1974；van Hoogevest & de Kruijff，1978）。这项工作得到了加拿大自然科学和工程研究委员会（U109）、美国国立卫生研究院（NCI Grant CA14554 和 NIAIDGrant AI16228）以及西安大略大学学术发展基金的支持。多烯抗生素在体内和培养中对哺乳动物细胞产生多种影响（Medoff 等，1983），可能涉及不止一种机制。因此，我们对更详细地表征多烯抗生素与活细胞膜的相互作用感兴趣。膜成分扩散的测量代表了一种研究其动态相互作用的方法，例如通过与缓慢移动的结构结合（Elson & Reidler，1979）。我们最近报道了两性霉素 B（Petersen，1983）、制霉菌素和匹马霉素（Petersen，1985）的硝基苯并恶二唑衍生物的合成和表征，并表征了这些衍生物中有趣且潜在有用的分子内荧光能量转移过程（Petersen，1985）。在本文中，我们提供了扩散数据，为以下方面提供了证据：
Department of Chemistry, The University of Western Ontario, London, Ontario, N6A 5B7 Canada Received April 24, 1985 abstract: Diffusion of a nitrobenzoxadiazole derivative of the polyene antibiotic nystatin in themembranes of L cells is found to depend on the concentration of nystatin in the membrane. Its diffusion coefficient measured by fluorescence photobleaching decreases hyperbolically as the concentration of nystatin is increased. This behavior is reproduced when the concentration of the derivative is increased. In contrast, diffusion of a nitrobenzoxadiazole derivative of a phospholipid is insensitive tothe nystatin concentration under these conditions. The nystatin-specific diffusion changes can be understood if nystatin exists in a monomer-micelle equilibrium within the membrane but cannot be accounted for by binding or phase partitioning.^ íystatin is one of several polyene antibiotics used clinically as an antifungal agent (Hammond, 1977; Medoff et al., 1983). These drugs are known to be membrane-active agents which can induce K+ leakage and cell lysis in yeast, erythrocytes, and mammalian cells including murine L cells (Gale, 1974). A large body of work with model membranes [reviewed by Hammond (1977)] has led to the suggestion that polyene antibiotics, such as nystatin and amphotericin B, associate with sterols in the membrane to form transmembrane pores (de Kruijff & Demel, 1974; van Hoogevest & de Kruijff, 1978). tThis work was supported by the Natural Sciences and Engineering Research Council of Canada (Grant U109), by the National Institutes of Health (NCI Grant CA14554 and NIAIDGrant AI16228), and by the Academic Development Fund of The University of Western Ontario.The polyene antibiotics produce a variety of effects on mammalian cells in vivo and in culture (Medoff et al., 1983) perhaps involving more than one mechanism. Accordingly, we have become interestedin characterizing in more detail the interactions of polyene antibiotics with membranes of living cells. Measurements of diffusion of membrane components represent one approach to studying their dynamic interactions through, for example, binding to slowly moving structures (Elson & Reidler, 1979). We have recently reported the synthesis and characterization of nitrobenzoxadiazole deriv-atives of amphotericin B (Petersen, 1983), nystatin, and pimaricin (Petersen, 1985) and have characterized an interesting and potentially useful intramolecular fluorescence energy transfer process in these derivatives (Petersen, 1985). In this paper, we present diffusion data which provide evidence for