Interaction between microcystins of different hydrophobicities and lipid monolayers

Interaction between microcystins of different hydrophobicities and lipid monolayers
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DOI:
10.1016/s0041-0101(02)00315-x
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发表时间:
2003-03-01
期刊:
影响因子:
2.8
通讯作者:
Meriluoto, JAO
Meriluoto, JAO
中科院分区:
医学4区
文献类型:
--
作者:
Vesterkvist, PSM;Meriluoto, JAO

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微囊藻毒素(microcystiins, MC)是一类由某些蓝藻(blue-green algae)产生的两相肽肝毒素和蛋白磷酸酶抑制剂。微囊藻毒素被认为需要一个主动的转运机制来穿透动物细胞的质膜。在这项研究中,表面恒压技术表明,两种更疏水的微囊藻毒素MC-LF(含亮氨酸和苯丙氨酸)和MC-LW(含亮氨酸和色氨酸)在鸡蛋磷脂酰胆碱-胆固醇(摩尔比7:3)单层上的表面活性高于更亲水的MC-LR(含亮氨酸和精氨酸)。使用1-[4-(三甲胺)苯基]-六-1,3,5-三烯(TMA-DPH)的荧光各向异性测量来评估存在毒素时模型膜流动性或脂质堆积的变化。这三种毒素均引起TMA-DPH稳态各向异性的降低,表明毒素与细胞膜相互作用。MC-LF和MC-LW的各向异性变化比MC-LR更明显。此外,MC-LW中Trp的荧光发射最大值略微向较短波长偏移,与脂质囊泡相互作用时强度增强,表明MC-LW中的单个Trp在与脂质囊泡相互作用时进入了更非极性的环境。亲水性和疏水性微囊藻毒素的差异可能导致嗜器官性、毒性动力学和生物蓄积的变化。2003爱思唯尔科学有限公司版权所有。
Microcystins (MC) are a group of amphiphatic peptide hepatotoxins and protein phosphatase inhibitors produced by certain cyanobacteria (blue-green algae). Microcystins are believed to require an active transport mechanism to penetrate the plasma membranes of animal cells. In this study the surface barostat technique showed that two more hydrophobic microcystins MC-LF, containing Leu and Phe, and MC-LW, containing Leu and Trp, had a higher surface activity on an egg phosphatidylcholine-cholesterol (7:3, molar ratio) monolayer as compared to that of a more hydrophilic variant MC-LR, containing Leu and Arg. Fluorescence anisotropy measurements of 1-[4-(trimethylamine)phenyl]-hexa-1,3,5-trien (TMA-DPH) were used to assess changes in the fluidity or lipid packing of model membranes in the presence of toxins. All three toxins caused a decrease in the steady-state anisotropy of TMA-DPH, suggesting that the toxins interacted with the membranes. The change in anisotropy was more pronounced for MC-LF and MC-LW than for MC-LR. Moreover, the fluorescence emission maximum of Trp in MC-LW was shifted slightly towards a shorter wavelength and the intensity was enhanced when allowed to interact with lipid vesicles, suggesting that the single Trp in MC-LW moved into a more unpolar environment when interacting with the vesicles. The differences between hydrophilic and hydrophobic microcystins could result in changes in organotropism, toxicokinetics and bioaccumulation. (C) 2003 Elsevier Science Ltd. All rights reserved.