Membrane effects of aminoglycoside antibiotics measured in liposomes containing the fluorescent probe, 1-anilino-8-naphthalene sulfonate.
Membrane effects of aminoglycoside antibiotics measured in liposomes containing the fluorescent probe, 1-anilino-8-naphthalene sulfonate.
复制标题
在含有荧光探针 1-苯胺基-8-萘磺酸盐的脂质体中测量氨基糖苷类抗生素的膜效应。
DOI：
10.1016/0005-2736(86)90484-0
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Weiner,N
中科院分区：
文献类型：
--
作者：
Au,S;Schacht,J;Weiner,N
以1-苯胺基-8-萘磺酸钠（ANS）为荧光探针，研究了氨基糖苷类抗生素对膜的干扰机制。在存在低（1 μM）和高（3 mM）浓度钙的情况下，用氨基糖苷类对PC和不同阴离子磷脂（1：1至15：1摩尔比）的脂质体进行挑战。含有PIP 2的脂质体在高浓度和低浓度的钙存在下以及在所有测试的PC：PIP 2摩尔比下显示出最大的药物诱导的ANS荧光变化。含有其他阴离子磷脂（PS，PI和PIP 2）的脂质体对氨基糖苷类在3 mM钙的存在下或当PC与阴离子脂质的比例增加到10：1时不反应。氨基糖苷类诱导的ANS荧光的变化不是由于ANS的发射光谱的任何变化，也不是量子产率的变化，也不是由于ANS的结合亲和力的变化。结论：氨基糖苷类药物与PIP 2的特异性相互作用导致了PC和PIP 2的相分离，从而增加了PC：PIP 2脂质体中ANS的结合位点。
The mechanism of membrane disturbance by aminoglycoside antibiotics was investigated in liposomes containing the fluorescent probe, 1-anilino-8-naphthalene sulfonate (ANS). Liposomes of PC and different anionic phospholipids (1:1 to 15:1 molar ratios) were challenged with aminoglycosides in the presence of low (1 μM) and high (3 mM) concentrations of calcium. Liposomes containing PIP2showed the greatest drug-induced changes in ANS fluorescence in the presence of high and low concentrations of calcium and at all PC:PIP2molar ratios tested. Liposomes containing other anionic phospholipids (PS, PI and PIP2) were not reactive toward aminoglycosides in the presence of 3 mM calcium or when the ratio of PC to anionic lipid was increased to 10:1. The aminoglycoside-induced changes of ANS flouorescence were not due to any changes in the emission spectrum of ANS, nor to changes in quantum yield, nor to a change in the binding affinity of ANS. It is concluded that a specific aminoglycoside-PIP2interaction results in phase separation of PC and PIP2and thus increases the number of available ANS binding sites in PC:PIP2liposomes.