Fa N, Ronkart S, Schanck A, Deleu M, Gaigneaux A, Goormaghtigh E, Mingeot-Leclercq M-P
Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, 73.70 Avenue E. Mounier 73, B-1200 Brussels, Belgium.
Chem Phys Lipids. 2006 Oct;144(1):108-16. doi: 10.1016/j.chemphyslip.2006.08.002. Epub 2006 Aug 15.
Azithromycin is a macrolide antibiotic known to bind to lipids and to affect endocytosis probably by interacting with lipid membranes [Tyteca, D., Schanck, A., Dufrene, Y.F., Deleu, M., Courtoy, P.J., Tulkens, P.M., Mingeot-Leclercq, M.P., 2003. The macrolide antibiotic azithromycin interacts with lipids and affects membrane organization and fluidity: studies on Langmuir-Blodgett monolayers, liposomes and J774 macrophages. J. Membr. Biol. 192, 203-215]. In this work, we investigate the effect of azithromycin on lipid model membranes made of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Thermal transitions of both lipids in contact with azithromycin are studied by (31)P NMR and DSC on multilamellar vesicles. Concerning the DPPC, azithromycin induces a suppression of the pretransition whereas a phase separation between the DOPC and the antibiotic is observed. For both lipids, the enthalpy associated with the phase transition is strongly decreased with azithromycin. Such effects may be due to an increase of the available space between hydrophobic chains after insertion of azithromycin in lipids. The findings provide a molecular insight of the phase merging of DPPC gel in DOPC fluid matrix induced by azithromycin [Berquand, A., Mingeot-Leclercq, M.P., Dufrene, Y.F., 2004. Real-time imaging of drug-membrane interactions by atomic force microscopy. Biochim. Biophys. Acta 1664, 198-205] and could help to a better understanding of azithromycin-cell interaction.
阿奇霉素是一种大环内酯类抗生素，已知它能与脂质结合，并可能通过与脂质膜相互作用来影响内吞作用[泰泰卡，D.，尚克，A.，迪弗雷内，Y.F.，德勒，M.，库尔图瓦，P.J.，图尔肯斯，P.M.，明热奥 - 勒克莱尔克，M.P.，2003年。大环内酯类抗生素阿奇霉素与脂质相互作用并影响膜组织和流动性：对朗缪尔 - 布洛杰特单层膜、脂质体和J774巨噬细胞的研究。《膜生物学杂志》192，203 - 215]。在这项工作中，我们研究了阿奇霉素对由1,2 - 二油酰 - sn - 甘油 - 3 - 磷酸胆碱（DOPC）或1,2 - 二棕榈酰 - sn - 甘油 - 3 - 磷酸胆碱（DPPC）制成的脂质模型膜的影响。通过多片层囊泡的（31）P核磁共振和差示扫描量热法研究了与阿奇霉素接触的两种脂质的热转变。关于DPPC，阿奇霉素会抑制预转变，而观察到DOPC与抗生素之间的相分离。对于这两种脂质，与相变相关的焓都因阿奇霉素而大幅降低。这种效应可能是由于阿奇霉素插入脂质后疏水链之间可用空间的增加。这些发现为阿奇霉素诱导的DPPC凝胶在DOPC流体基质中的相融合提供了分子层面的见解[贝昆德，A.，明热奥 - 勒克莱尔克，M.P.，迪弗雷内，Y.F.，2004年。通过原子力显微镜实时成像药物 - 膜相互作用。《生物化学与生物物理学报》1664，198 - 205]，并有助于更好地理解阿奇霉素与细胞的相互作用。
