Scavenger receptor BI mediates the selective uptake of oxidized cholesterol esters by rat liver
Scavenger receptor BI mediates the selective uptake of oxidized cholesterol esters by rat liver
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DOI：
10.1074/jbc.274.13.8893
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发表时间：
1999-03-26
影响因子：
4.8
通讯作者：
van Berkel, TJC
中科院分区：
文献类型：
--
作者：
Fluiter, K;Sattler, W;van Berkel, TJC
高密度脂蛋白（HDL）具有保护低密度脂蛋白（LDL）免受氧化的作用，LDL中的氧化胆固醇酯可转化为HDL，并在体内被肝脏和肾上腺有效地、选择性地从血液循环中清除。在本研究中，我们调查是否清道夫受体BI（SR-BI）负责这一过程。在注射后30分钟，氧化胆固醇酯从HDL的肝脏和肾上腺的选择性摄取分别为2.3和2.6倍，比天然胆固醇酯，而其他组织没有显着差异。分离的肝实质细胞从HDL中选择性摄取氧化胆固醇酯可被氧化LDL阻断75%，被磷脂酰丝氨酸脂质体阻断50%，这两种脂质体都是SR-BI的已知底物。当大鼠用雌二醇和高胆固醇饮食处理时，肝实质细胞从HDL中摄取氧化胆固醇酯分别减少64%和81%，而枯否细胞分别显示660和475%的增加。氧化胆固醇酯摄取的这些对比变化伴随着实质细胞和枯否细胞SR-BI表达的类似对比变化。在SR-BI转染的中国仓鼠卵巢细胞中分析了SR-BI介导的氧化和天然胆固醇酯的选择性摄取速率。氧化型SR-BI介导的选择性摄取是天然胆固醇酯的3.4倍（孵育30 min）。它的结论是，除了天然胆固醇酯的选择性摄取，SR-BI是负责高效率的选择性摄取氧化胆固醇酯从HDL，从而形成一个重要的介体在HDL相关的保护系统致动脉粥样硬化的氧化胆固醇酯。
High density lipoprotein (HDL) can protect low density lipoprotein (LDL) against oxidation, Oxidized cholesterol esters from LDL can be transferred to HDL and efficiently and selectively removed from the blood circulation by the liver and adrenal in vivo. In the present study, we investigated whether scavenger receptor BI (SR-BI) is responsible for this process. At 30 min after injection, the selective uptake of oxidized cholesterol esters from HDL for liver and adrenal was 2.3- and 2.6-fold higher, respectively, than for native cholesterol esters, whereas other tissues showed no significant difference. The selective uptake of oxidized cholesterol esters from HDL by isolated liver parenchymal cells could be blocked for 75% by oxidized LDL and for 50% by phosphatidylserine liposomes, both of which are known substrates of SR-BI,In vivo uptake of oxidized cholesterol esters from HDL by parenchymal cells decreased by 64 and 81% when rats were treated with estradiol and a high cholesterol diet, respectively, whereas Kupffer cells showed 660 and 475% increases, respectively. These contrasting changes in oxidized cholesterol ester uptake were accompanied by similar contrasting changes in SR-BI expression of parenchymal and Kupffer cells. The rates of SR-BI-mediated selective uptake of oxidized and native cholesterol esters were analyzed in SR-BI-transfected Chinese hamster ovary cells. SR-BI-mediated selective uptake was 3.4-fold higher for oxidized than for native cholesterol esters (30 min of incubation). It is concluded that in addition to the selective uptake of native cholesterol esters, SR-BI is responsible for the highly efficient Selective uptake of oxidized cholesterol esters from HDL and thus forms an essential mediator in the HDL-associated protection system for atherogenic oxidized cholesterol esters.