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Mechanism of Biological Membrane Damage Induced by Amphiphilic Drugs and Peptides

两亲性药物和肽诱导生物膜损伤的机制

基本信息

批准号：
01571178
负责人：
KATSU Takashi
金额：
$ 1.34万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

In this research, the K^+ permaebility-increasing actions of various amphiphilic drugs and peptides on biomembranes were examined. Cells used were human erythrocytes, Staphylococcus aureus, Escherichia coli and rat peritoneal mast cells. We described here the results of mastoparan as a typical example. This peptide did not efficiently increase the K^+ permeability of cells except for S. aureus. The release of membrane phospholipids was also observed from S. Baureus cells in the concentra tion range of the permeability enhancement. Mastoparan stimulated histamine release from mast cells, independently of a small efflux of K^+. Mastoparan became markedly effective to E. coli cells whose outer membrane structure was chemically disrupted beforehand, showing that the peptide can enhance the permeability of the cytoplasmic membranes of both Gram-positive and -negative bacteria. In experiments using liposomes, mastoparan increased the permeability of the liposomes composed of egg phoshatidylethanolamine and egg phosphatidylglycerol, which are the lipid constituents of the cytoplasmic membrane of E. colls, while it showed a weak activity to the liposomes composed of egg phosphatidylcholine and cholesterol. The latter result related closely to the fact that this peptide acted weakly on erythrocytes and mast cells in which acidic lipids constitute a minor portion. Mastoparan decreased the phase transition temperature of dipalmitoylphosphatidylglycerol liposomes. but it did not affect that of dipalmitoylphosphatidylcholine liposomes. These results indicate that mastoparan penetrated into membranes mainly containing acidic phospholipids and disrupted the membrane structure to increase the permeability. The results of other peptides can be seen through referencEs described on the back of this paper.

在本研究中，考察了各种两亲性药物和多肽对生物膜的K^+渗透率增加作用。使用的细胞是人红细胞、金黄色葡萄球菌、大肠杆菌和大鼠腹膜肥大细胞。我们在这里描述的结果mastoparan作为一个典型的例子。该肽不能有效地增加除S外的细胞的K^+渗透性。金黄色。同时还观察到S.金黄色葡萄球菌细胞在浓度范围内通透性增强。Mastoparan刺激肥大细胞释放组胺，而不依赖于少量K^+外流。Mastoparan对E.大肠杆菌细胞，其外膜结构被预先化学破坏，表明该肽可以增强革兰氏阳性菌和革兰氏阴性菌细胞质膜的渗透性。在使用脂质体的实验中，mastoparan增加了由卵磷脂酰乙醇胺和卵磷脂酰甘油组成的脂质体的渗透性，卵磷脂酰乙醇胺和卵磷脂酰甘油是大肠杆菌细胞质膜的脂质成分。colls组成的脂质体，而对卵磷脂和胆固醇组成的脂质体则表现出较弱的活性。后者的结果密切相关的事实，即这种肽对红细胞和肥大细胞，其中酸性脂质构成的一小部分弱。Mastoparan降低了二棕榈酰磷脂酰甘油脂质体的相变温度。但对二棕榈酰磷脂酰胆碱脂质体的影响不明显。这些结果表明，mastoparan渗透到主要含有酸性磷脂的膜中，并破坏膜结构以增加渗透性。其他肽的结果可以通过本文背面描述的参考文献看到。