ANATOMY OF AMPHOTERICIN-B-CHOLESTEROL PORES IN LIPID BILAYER MEMBRANES
ANATOMY OF AMPHOTERICIN-B-CHOLESTEROL PORES IN LIPID BILAYER MEMBRANES
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DOI：
10.1038/ki.1973.126
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发表时间：
1973-01-01
影响因子：
19.6
通讯作者：
ANDREOLI, TE
中科院分区：
文献类型：
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作者：
ANDREOLI, TE
Lampen [1]和Kinsky、Luse和货车Deenen [2]之前总结的大量实验证据表明，多烯抗生素（如阿替霉素B）对真菌和其他敏感微生物的溶解作用[31]与抗生素与膜结合甾醇相互作用产生的质膜溶质渗透性增加有关。同样，抗生素增加蟾蜍膀胱对尿素、硫脲、钾和氯化物的渗透性[4，5]，以及红细胞对钾[6]、钠、氯化物和小于蔗糖的亲水性非电解质的渗透性[7，8]。此外，在使用阿替霉素B的全身治疗过程中观察到的低钾血症[9-121]、肾钠消耗[11]和梯度限制性肾小管酸中毒[13]可能是抗生素对远端肾单位转运事件的类似作用的结果。因此，探讨阿替霉素B改变天然膜渗透性的可能机制似乎是合理的，在本[14-20]和其他[21-23]实验室中使用的解决该问题的一种方法是分析多烯抗生素对Mueller等人[24]首次描述的平面脂质双层膜中耗散转运过程的影响。本社论的目的是双重的：第一，总结某些观察结果表明，相互作用的阿朴霉素B（或制霉菌素，一种结构与抗生素B几乎相同的多烯抗生素[25，26]）与膜结合的甾醇或其他适当的甾醇[161]作用，导致水孔的形成;第二，提供了一个关于阿替西霉素B-胆固醇孔的部分结构及其对膜功能影响的假设[20]。阿替霉素B和胆固醇的立体化学。图1显示了化学结构和绝对构型
There is abundant experimental evidence, summarized previously by Lampen [1] and by Kinsky, Luse and Van Deenen [2], which indicates that the lytic effects of polyene antibiotics such as amphotericin B on fungi and other susceptible microorganisms [31 are referable to in-creases in the solute permeability of plasma membranes produced by interactions of the antibiotic with membranebound sterols. Similarly, the antibiotic increases the per-meability of the toad urinary bladder to urea, thiourea, potassium and chloride [4, 5] and of the erythrocyte to potassium [6], sodium, chloride and hydrophilic non-electrolytes smaller than sucrose [7, 8]. Further, it may be that the hypokalemia [9—121, renal sodium wasting [11], and gradient-limited renal tubular acidosis [13] observed in the course of systemic therapy with amphotericin B may be the consequence of comparable effects of the antibiotic on transport events in the distal nephron. Accordingly, it seems reasonable to inquire into the possible mechanisms by which amphotericin B modifies the permeability of natural membranes.One approach to the problem, utilized in this [14—20] and other [21—23] laboratories, has been to analyze the effects of polyene antibiotics on dissipative transport processes in planar lipid bilayer membranes of the type first described by Mueller et al [24]. The purpose of the present editorial is two-fold: first, to summarize certain of the observations which indicate that the interactions of amphotericin B (or nystatin, a polyene antibiotic nearly identical in structure [25, 26] to amphotericin B) with membrane-bound choles-terol or other appropriate sterols [161 result in the formation of aqueous pores; and second, to provide an hypothesis for the partial structure of amphotericin B-choles-terol pores and their effect on membrane function [20]. Stereochemistry of amphotericin B and cholesterol. Fig. 1 indicates the chemical structure and absolute configuration