Fluiter K, Sattler W, De Beer M C, Connell P M, van der Westhuyzen D R, van Berkel T J
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, University of Leiden, Sylvius Laboratories, P. O. Box 9503, 2300 RA Leiden, The Netherlands.
J Biol Chem. 1999 Mar 26;274(13):8893-9. doi: 10.1074/jbc.274.13.8893.
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.
高密度脂蛋白（HDL）可保护低密度脂蛋白（LDL）不被氧化。来自LDL的氧化胆固醇酯可转移至HDL，并在体内被肝脏和肾上腺有效且选择性地从血液循环中清除。在本研究中，我们调查了清道夫受体BI（SR-BI）是否参与此过程。注射后30分钟，肝脏和肾上腺对HDL中氧化胆固醇酯的选择性摄取分别比天然胆固醇酯高2.3倍和2.6倍，而其他组织则无显著差异。分离的肝实质细胞对HDL中氧化胆固醇酯的选择性摄取可被氧化LDL阻断75%，被磷脂酰丝氨酸脂质体阻断50%，这两者均为已知的SR-BI底物。当大鼠分别用雌二醇和高胆固醇饮食处理时，肝实质细胞对HDL中氧化胆固醇酯的体内摄取分别下降了64%和81%，而库普弗细胞则分别增加了660%和475%。氧化胆固醇酯摄取的这些相反变化伴随着实质细胞和库普弗细胞SR-BI表达的类似相反变化。在转染了SR-BI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选择性摄取率。SR-BI介导的氧化胆固醇酯选择性摄取（孵育30分钟）比天然胆固醇酯高3.4倍。结论是，除了对天然胆固醇酯的选择性摄取外，SR-BI还负责从HDL中高效选择性摄取氧化胆固醇酯，因此在HDL相关的抗动脉粥样硬化氧化胆固醇酯保护系统中形成了一个重要的介质。
