The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation
The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation
复制标题
DOI：
10.1021/bi992543v
复制
发表时间：
2000-02-08
期刊：
影响因子：
2.9
通讯作者：
London, E
中科院分区：
文献类型：
--
作者：
Xu, XL;London, E
洗涤剂不溶性膜结构域富含饱和脂质和胆固醇，与许多生物学功能有关。为了了解胆固醇如何促进结构域形成，比较了各种甾醇和甾醇衍生物对饱和脂质二棕榈酰磷脂酰胆碱（DPPC）和不饱和脂质的荧光猝灭类似物的混合物中结构域形成的影响。淬灭测量表明，几种甾醇（胆固醇，二氢胆固醇，表胆固醇，和25-羟基胆固醇）促进DPPC富集域的形成。其他甾醇和甾醇衍生物对结构域形成几乎没有影响（胆甾烷和羊毛甾醇），或者令人惊讶地，强烈抑制它（粪前列烷醇，雄甾烯醇，胆固醇硫酸酯和4-胆甾烯酮）。甾醇对结构域形成的影响与其对DPPC不溶性的影响密切相关。那些甾醇，促进结构域形成增加DPPC的不溶性，而那些甾醇，抑制结构域形成降低DPPC的不溶性。甾醇对DPPC囊泡中二苯基己三烯荧光偏振的影响也与甾醇的结构有关。这些实验表明甾醇对饱和脂质形成紧密堆积（即，在脂质彼此紧密堆积的意义上是紧密的）并且有序状态是它们对域形成的影响的关键。那些促进饱和脂质紧密堆积的甾醇促进结构域形成，而那些抑制饱和脂质紧密堆积的甾醇抑制结构域形成。一些甾醇抑制结构域形成的能力（即，作为“抗胆固醇剂”）应该是检查细胞中结构域形成和性质的有价值的工具。
Detergent-insoluble membrane domains, enriched in saturated lipids and cholesterol, have been implicated in numerous biological functions. To understand how cholesterol promotes domain formation, the effect of various sterols and sterol derivatives on domain formation in mixtures of the saturated lipid dipalmitoylphosphatidylcholine (DPPC) and a fluorescence quenching analogue of an unsaturated lipid was compared. Quenching measurements demonstrated that several sterols (cholesterol, dihydrocholesterol, epicholesterol, and 25-hydroxycholesterol) promote formation of DPPC-enriched domains. Other sterols and sterol derivatives had little effect on domain formation (cholestane and lanosterol) or, surprisingly, strongly inhibit it (coprostanol, androstenol, cholesterol sulfate, and 4-cholestenone). The effect of sterols on domain formation was closely correlated with their effects on DPPC insolubility. Those sterols that promoted domain formation increased DPPC insolubility, whereas those sterols that inhibit domain formation decreased DPPC insolubility. The effects of sterols on the fluorescence polarization of diphenylhexatriene incorporated into DPPC-containing vesicles were also correlated with sterol structure. These experiments indicate that the effect of sterol on the ability of saturated lipids to form a tightly packed (i.e., tight in the sense that the lipids are closely packed with one another) and ordered state is the key to their effect on domain formation. Those sterols that promote tight packing of saturated lipids promote domain formation, while those sterols that inhibited tight packing of saturated lipids inhibited domain formation. The ability of some sterols to inhibit domain formation (i.e., act as "anti-cholesterols'') should be a valuable tool for examining domain formation and properties in cells.