Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile
Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile
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DOI：
10.1074/jbc.274.47.33398
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发表时间：
1999-11-19
影响因子：
4.8
通讯作者：
Tall, AR
中科院分区：
文献类型：
--
作者：
Ji, Y;Wang, N;Tall, AR
组织清除血浆脂蛋白中的游离胆固醇具有重要的定量意义，但目前尚不清楚这是被动的还是受体介导的。基于我们的发现，清道夫受体BI(SR-BI)促进高密度脂蛋白(HDL)和细胞之间的游离胆固醇(FC)交换，我们使用[C-14]FC和[H-3]胆固醇酯(CE)标记的高密度脂蛋白([C-14]FC和[H-3]胆固醇酯(CE)标记的高密度脂蛋白)，在肝脏SR-BI表达增加(SR-BI转基因(TG))或降低(SR-BI减弱(ATT))的小鼠中，测试SR-BI是否会影响FC的体内运动。与野生型小鼠相比，SR-BI Tg小鼠的RBL Fc初始清除率增加了72%，SR-BI ATT小鼠的初始清除率降低了53%，而apoA-I基因敲除小鼠的初始清除率没有变化。FC向非高密度脂蛋白的转移和FC的酯化作用很小，不能解释差异。SR-BI Tg小鼠的肝脏对FC的摄取增加了34%，而SR-BI ATT小鼠的Fc摄取减少了22%。CE清除和摄取的结果相似，但速度要慢得多。SR-BI-TG原代肝细胞对HDLFC和CE的摄取分别是对照组的2.2倍和2.6倍(孵育1小时)。在SR-BI TG小鼠中，[C-14]Fc的初始胆汁分泌显著增加，而[H-3]Fc的增加在稍有延迟后出现。因此，在小鼠体内，高密度脂蛋白Fc从血浆中清除的主要部分是由SR-BI介导的。
The clearance of free cholesterol from plasma lipoproteins by tissues is of major quantitative importance, but it is not known whether this is passive or receptor-mediated. Based on our finding that scavenger receptor BI (SR-BI) promotes free cholesterol (FC) exchange between high density lipoprotein (HDL) and cells, we tested whether SR-BI would effect FC movement in vivo using [C-14]FC- and [H-3]cholesteryl ester (CE)-labeled HDL in mice with increased (SR-BI transgenic (Tg)) or decreased (SR-BI attenuated (att)) hepatic SR-BI expression. The initial clearance of RBL FC was increased in SR-BI Tg mice by 72% and decreased in SR-BI att mice by 53%, but was unchanged in apoA-I knockout mice compared with wild-type mice. Transfer of FC to non-HDL and esterification of FC were minor and could not explain differences. The hepatic uptake of FC was increased in SR-BI Tg mice by 34% and decreased in SR-BI att mice by 22%. CE clearance and uptake gave similar results, but with much slower rates. The uptake of HDL FC and CE by SR-BI Tg primary hepatocytes was increased by 2.2- and 2.6-fold (1-h incubation), respectively, compared with control hepatocytes. In SR-BI Tg mice, the initial biliary secretion of [C-14]FC was markedly increased, whereas increased [H-3]FC appeared after a slight delay. Thus, in the mouse, a major portion of the clearance of HDL FC from plasma is mediated by SR-BI.