Thomas P D, Poznansky M J
Department of Physiology, University of Alberta, Edmonton, Canada.
Biochem J. 1988 Apr 1;251(1):55-61. doi: 10.1042/bj2510055.
The effect of lipid composition on the rate of cholesterol movement between cellular membranes is investigated using lipid vesicles. The separation of donor and acceptor vesicles required for rate measurement is achieved by differential centrifugation so that the lipid effect can be quantified in the absence of a charged lipid generally used for ion-exchange-based separation. The rate of cholesterol transfer from small unilamellar vesicles (SUVs) containing 50 mol% cholesterol to a common large unilamellar vesicle (LUV) acceptor containing 20 mol% cholesterol decreases with increasing mol% of sphingomyelin in the SUVs, while phosphatidylethanolamine and phosphatidylserine have no appreciable effect at physiologically relevant levels. There is a large decrease in rate when phosphatidylethanolamine constitutes 50 mol% of donor phospholipids. Interestingly, gangliosides which have the same hydrocarbon moiety as sphingomyelin exert an opposite effect. The effect of spingomyelin seems to be mediated by its ability to decrease the fluidity of the lipid matrix, while that of gangliosides may arise from a weakening of phosphatidylcholine-cholesterol interactions or from a more favourable (less polar) microenvironment for the desorption of cholesterol provided by the head-group interactions involving sugar residues. If the effect of asymmetric transbilayer distribution of lipids is taken into consideration, the observed composition-dependent rate changes could partly account for the large difference in the rates of cholesterol desorption from the inner and outer layers of plasma membrane. Such rate differences may be responsible for an unequal steady-state distribution of cholesterol among various cellular membranes and lipoproteins.
利用脂质囊泡研究了脂质组成对细胞膜间胆固醇移动速率的影响。通过差速离心实现了速率测量所需的供体囊泡和受体囊泡的分离，从而能够在不存在通常用于基于离子交换分离的带电脂质的情况下对脂质效应进行定量。胆固醇从含有50摩尔%胆固醇的小单层囊泡（SUV）转移到含有20摩尔%胆固醇的普通大单层囊泡（LUV）受体的速率，随着SUV中鞘磷脂摩尔%的增加而降低，而在生理相关水平下，磷脂酰乙醇胺和磷脂酰丝氨酸没有明显影响。当磷脂酰乙醇胺占供体磷脂的50摩尔%时，速率大幅下降。有趣的是，与鞘磷脂具有相同烃基部分的神经节苷脂产生相反的作用。鞘磷脂的作用似乎是由其降低脂质基质流动性的能力介导的，而神经节苷脂的作用可能源于磷脂酰胆碱 - 胆固醇相互作用的减弱，或者源于涉及糖残基的头部基团相互作用为胆固醇解吸提供的更有利（极性较小）的微环境。如果考虑脂质不对称跨膜分布的影响，观察到的组成依赖性速率变化可能部分解释了胆固醇从质膜内层和外层解吸速率的巨大差异。这种速率差异可能导致胆固醇在各种细胞膜和脂蛋白之间的稳态分布不均。
