MEMBRANE-DAMAGING ACTION OF STAPHYLOCOCCAL ALPHA-TOXIN ON PHOSPHOLIPID-CHOLESTEROL LIPOSOMES

MEMBRANE-DAMAGING ACTION OF STAPHYLOCOCCAL ALPHA-TOXIN ON PHOSPHOLIPID-CHOLESTEROL LIPOSOMES
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DOI:
10.1016/0005-2736(87)90065-4
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发表时间:
1987-04-23
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子:
--
通讯作者:
YASUDA, T
YASUDA, T
中科院分区:
其他
文献类型:
--
作者:
WATANABE, M;TOMITA, T;YASUDA, T

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以不同的磷脂和胆固醇为原料,制备了载羧基荧光素(内标记物)的多层脂质体,研究了葡萄球菌α毒素对细胞膜的损伤机制。当α毒素浓度高于1或8 μ m时,磷脂酰胆碱或鞘磷脂与胆固醇组成的脂质体与α毒素结合,并以剂量依赖的方式释放羧荧光素。分别g / ml。相反,其他由磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰甘油或磷脂酰肌醇加胆固醇组成的脂质体即使在高达870 μ g/ml的高浓度下也不敏感。通过在脂质体膜中插入磷脂酰胆碱,使含有磷脂酰丝氨酸或磷脂酰甘油的不敏感脂质体对α -毒素敏感。此外,磷胆碱抑制毒素诱导的标志物从脂质体释放。这些结果表明,含有胆碱的磷脂是α毒素与脂质体膜相互作用所必需的。含磷脂酰胆碱或鞘磷脂的脂质体的敏感性随脂质体中胆固醇含量的增加而增加。基于这些结果,我们提出含胆碱磷脂可能是负责毒素-膜相互作用的膜成分或结构,导致膜损伤。此外,胆固醇可能作为膜的结构成分促进α -毒素与膜之间的相互作用。
The mechanism of membrane damage by staphylococcal alpha-toxin was studied using carboxyfluorescein (internal marker)-loaded multilamellar liposomes prepared from various phospholipids and cholesterol. Liposomes composed of phosphatidylcholine or sphingomyelin and cholesterol bound alpha-toxin and released carboxyfluorescein in a dose dependent manner, when they were exposed to alpha-toxin of concentrations higher than 1 or 8 .mu.g/ml, respectively. In contrast, the other liposomes composed of phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol or phosphatidylinositol plus cholesterol were not susceptible to the toxin even at high concentrations up to 870 .mu.g/ml. The insensitive liposomes containing either phosphatidylserine or phosphatidylglycerol were made sensitive to alpha-toxin by inserting phosphatidylcholine into the liposomal membranes. In addition, phosphorylcholine inhibited the toxin-induced marker release from liposomes. These results indicated that the choline-containing phospholipids are required for the interaction between alpha-toxin and liposomal membranes. Susceptibility of liposomes containing phosphatidylcholine or sphingomyelin increased with the increase in cholesterol contents of the liposomes. Based on these results, we propose that the choline-containing phospholipids are possible membrane components or structures responsible for the toxin-membrane interaction, which leads to damage of membranes. Furthermore, cholesterol may facilitate the interaction between alpha-toxin and membrane as a structural component of the membrane.