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不同药物对细胞色素c - 磷脂双分子层膜的影响。

Effect of different drugs on a cytochrome c--phospholipid bilayer membrane.

作者信息

Singer M A

出版信息

Can J Physiol Pharmacol. 1978 Aug;56(4):555-63. doi: 10.1139/y78-089.

DOI:10.1139/y78-089
PMID:210916
Abstract

Liposomes were prepared from dipalmitoyl phosphatidylcholine and dicetylphosphate and their interaction with the extrinsic membrane protein cytochrome c examined in terms of changes in 22Na permeability, electrophoretic mobility, protein binding, and motion of an incorporated spin label. The amount of cytochrome c bound displays no significant temperature dependence over the temperature range studied (from 30 to 55 degrees C) whereas cytochrome c causes an increase in 22Na efflux only above the phospholipid phase transition temperature. Interaction of the protein with the lipid vesicles causes no significant disturbance in the bilayer interior as monitored by the motion of the incorporated spin probe. The drugs 2,4-dinitrophenol and ethacrynic acid, both of which increase the magnitude of the vesicle negative charge, enhance both cytochrome c binding and its effect on 22Na permeability. In contrast, the local anesthetic dibucaine, which induces a positive surface charge on these liposomes, reduces both protein binding and the protein-induced increase in 22Na efflux. Finally, the chemicals butylated hydroxytoluene, 2-tert-butylphenol, and tert-butylbenzene, all of which cause early 'melting' of the phospholipid fatty acyl chains, block the capacity of cytochrome c to enhance 22Na permeability while having no effect on its binding to the vesicles.

摘要

脂质体由二棕榈酰磷脂酰胆碱和十六烷基磷酸酯制备而成,并根据²²Na通透性、电泳迁移率、蛋白质结合以及掺入的自旋标记物的运动变化,研究了它们与外在膜蛋白细胞色素c的相互作用。在所研究的温度范围内(30至55摄氏度),结合的细胞色素c的量没有明显的温度依赖性,而细胞色素c仅在磷脂相变温度以上才会导致²²Na外流增加。通过掺入的自旋探针的运动监测发现,蛋白质与脂质囊泡的相互作用对双层内部没有明显干扰。药物2,4 -二硝基苯酚和依他尼酸都会增加囊泡负电荷的大小,它们既能增强细胞色素c的结合,又能增强其对²²Na通透性的影响。相比之下,局部麻醉药丁卡因会在这些脂质体上诱导正表面电荷,它既能减少蛋白质结合,又能减少蛋白质诱导的²²Na外流增加。最后,化学物质丁基化羟基甲苯、2 -叔丁基苯酚和叔丁基苯都会导致磷脂脂肪酰链提前“熔化”,它们会阻断细胞色素c增强²²Na通透性的能力,而对其与囊泡的结合没有影响。

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Effect of different drugs on a cytochrome c--phospholipid bilayer membrane.不同药物对细胞色素c - 磷脂双分子层膜的影响。
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