Stelzer K J, Gordon M A
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas College of Health Science and Hospital, Kansas City.
Biochim Biophys Acta. 1988 Feb 8;938(1):114-20. doi: 10.1016/0005-2736(88)90128-9.
Fluorescence steady-state anisotropy and phase-modulation lifetime techniques have been utilized to study the interactions of pyrethroid compounds with fluid-phase phosphatidylcholine membranes containing the polypeptide gramicidin. This polypeptide is considered to be a model of hydrophobic regions of cellular integral membrane proteins. The pyrethroids disorder lipid packing in cellular membranes and gel-phase liposomes but do not disorder lipid packing in fluid-phase lipid (Stelzer, K.J. and Gordon, M.A. (1984) J. Immunopharmacol. 6, 381-410; (1985) Biochim. Biophys. Acta 812, 361-368) Irrespective of liposomal size, gramicidin incorporation resulted in a substantial increase in anisotropy of the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), in fluid phase lipid. In the absence of gramicidin, permethrin and three other pyrethroids, allethrin, cypermethrin and fenpropathrin, increased DPH anisotropy. In these fluid phase systems, as the protein:lipid ratio was increased, the extent of the pyrethroid-mediated increase in fluorescence anisotropy diminished. Also, the pyrethroids shortened DPH fluorescence lifetimes. At high gramicidin:lipid ratios, permethrin substantially lowered anisotropy in the fluid phase lipid, relative to controls. The data suggest that pyrethroids disturb fluid-phase lipids which have been promoted to a relative state of order by proximity to an integral membrane protein. This type of order is one which is represented by DPH fluorescence anisotropy. A model based on these results is proposed to explain the effects of pyrethroids on lipid packing order in cellular membranes, as determined by DPH fluorescence anisotropy.
荧光稳态各向异性和相位调制寿命技术已被用于研究拟除虫菊酯化合物与含有多肽短杆菌肽的液相磷脂酰胆碱膜之间的相互作用。这种多肽被认为是细胞整合膜蛋白疏水区域的模型。拟除虫菊酯会扰乱细胞膜和凝胶相脂质体中的脂质堆积，但不会扰乱液相脂质中的脂质堆积（Stelzer, K.J.和Gordon, M.A.（1984年）《免疫药理学杂志》6, 381 - 410；（1985年）《生物化学与生物物理学报》812, 361 - 368）。无论脂质体大小如何，短杆菌肽的掺入都会导致液相脂质中荧光探针1,6 - 二苯基 - 1,3,5 - 己三烯（DPH）的各向异性大幅增加。在没有短杆菌肽的情况下，氯菊酯和其他三种拟除虫菊酯，即丙烯菊酯、氯氰菊酯和甲氰菊酯，会增加DPH各向异性。在这些液相系统中，随着蛋白质与脂质比例的增加，拟除虫菊酯介导的荧光各向异性增加程度减小。此外，拟除虫菊酯会缩短DPH荧光寿命。在高短杆菌肽与脂质比例下，相对于对照，氯菊酯会大幅降低液相脂质中的各向异性。数据表明，拟除虫菊酯会扰乱因靠近整合膜蛋白而被促进到相对有序状态的液相脂质。这种有序状态是由DPH荧光各向异性所代表的。基于这些结果提出了一个模型来解释拟除虫菊酯对细胞膜中脂质堆积顺序的影响，该影响由DPH荧光各向异性测定。
