High Density Lipoprotein Phospholipid Composition Is a Major Determinant of the Bi-directional Flux and Net Movement of Cellular Free Cholesterol Mediated by Scavenger Receptor BI*
High Density Lipoprotein Phospholipid Composition Is a Major Determinant of the Bi-directional Flux and Net Movement of Cellular Free Cholesterol Mediated by Scavenger Receptor BI*
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DOI：
10.1074/jbc.m006924200
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发表时间：
2000-11
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影响因子：
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通讯作者：
P. Yancey;M. de la Llera-Moya;S. Swarnakar;Pascale Monzo;Seth M. Klein;M. Connelly;W. J. Johnson;David L. Williams;G. Rothblat
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作者：
P. Yancey;M. de la Llera-Moya;S. Swarnakar;Pascale Monzo;Seth M. Klein;M. Connelly;W. J. Johnson;David L. Williams;G. Rothblat
通过控制高密度脂蛋白（HDL）3磷脂酰胆碱和鞘磷脂含量，研究了HDL磷脂在清道夫受体BI（SR-BI）介导的游离胆固醇流动中的作用。磷脂酰胆碱和鞘磷脂富集HDL增强了SR-BI表达COS-7细胞胆固醇的净流出，但通过两种不同的机制。磷脂酰胆碱丰富的HDL增加流出，而鞘磷脂丰富减少流入的HDL胆固醇。虽然在对照（载体转染）COS-7细胞中观察到类似的趋势，但SR-BI过表达分别将HDL的磷脂酰胆碱和鞘磷脂富集的作用放大了25倍和2.8倍。通过使用富含磷脂酰胆碱和磷脂酶A2处理的HDL获得具有分级磷脂酰胆碱含量的HDL，我们表明SR-BI介导的胆固醇流出与HDL磷脂酰胆碱含量高度相关（r2 = 0.985）。不同HDL磷脂组成对SR-BI介导的游离胆固醇流量的影响与高亲和力结合SR-BI的Kd或B max值的变化无关。我们得出结论，SR-BI介导的游离胆固醇流量是高密度脂蛋白磷脂组合物高度敏感。因此，调节细胞SR-BI表达和HDL磷脂组成的局部修饰的因素将对胆固醇逆向转运产生很大影响。
The role of high density lipoprotein (HDL) phospholipid in scavenger receptor BI (SR-BI)-mediated free cholesterol flux was examined by manipulating HDL3phosphatidylcholine and sphingomyelin content. Both phosphatidylcholine and sphingomyelin enrichment of HDL enhanced the net efflux of cholesterol from SR-BI-expressing COS-7 cells but by two different mechanisms. Phosphatidylcholine enrichment of HDL increased efflux, whereas sphingomyelin enrichment decreased influx of HDL cholesterol. Although similar trends were observed in control (vector-transfected) COS-7 cells, SR-BI overexpression amplified the effects of phosphatidylcholine and sphingomyelin enrichment of HDL 25- and 2.8-fold, respectively. By using both phosphatidylcholine-enriched and phospholipase A2-treated HDL to obtain HDL with a graded phosphatidylcholine content, we showed that SR-BI-mediated cholesterol efflux was highly correlated (r 2 = 0.985) with HDL phosphatidylcholine content. The effects of varying HDL phospholipid composition on SR-BI-mediated free cholesterol flux were not correlated with changes in either the K d orB max values for high affinity binding to SR-BI. We conclude that SR-BI-mediated free cholesterol flux is highly sensitive to HDL phospholipid composition. Thus, factors that regulate cellular SR-BI expression and the local modification of HDL phospholipid composition will have a large impact on reverse cholesterol transport.