Webb Nancy R, Cai Lei, Ziemba Kristine S, Yu Jin, Kindy Mark S, van der Westhuyzen Deneys R, de Beer Frederick C
Department of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
J Lipid Res. 2002 Nov;43(11):1890-8. doi: 10.1194/jlr.m200173-jlr200.
Scavenger receptor class B type I (SR-BI) delivers cholesterol ester from HDL to cells via a selective uptake mechanism, whereby lipid is transferred from the core of the particle without concomitant degradation of the protein moiety. The precise metabolic fate of HDL particles after selective lipid uptake is not known. To characterize SR-BI-mediated HDL processing in vivo, we expressed high levels of this receptor in livers of apoA-I(-/-) mice by adenoviral vector gene transfer, and then injected the mice with a bolus of human HDL(2) traced with (125)I-dilactitol tyramine. HDL recovered from apoA-I(-/-) mice over-expressing SR-BI was significantly smaller than HDL recovered from control mice as measured by non-denaturing gel electrophoresis. When injected into C57BL/6 mice, these HDL "remnants" were rapidly converted to HDL(2)-sized lipoprotein particles, and were cleared from the plasma at a rate similar to HDL(2). In assays in cultured cells, HDL remnants did not stimulate ATP-binding cassette transporter A1-dependent cholesterol efflux. When mixed with mouse plasma ex vivo, HDL remnants rapidly converted to larger HDL particles. These studies identify a previously ill-defined pathway in HDL metabolism, whereby SR-BI generates small, dense HDL particles that are rapidly remodeled in plasma. This remodeling pathway may represent a process that is important in determining the rate of apoA-I catabolism and HDL-mediated reverse cholesterol transport.
I型清道夫受体B类（SR-BI）通过一种选择性摄取机制将高密度脂蛋白（HDL）中的胆固醇酯转运至细胞，在此过程中，脂质从颗粒核心转移，而蛋白质部分不发生降解。选择性摄取脂质后HDL颗粒的确切代谢命运尚不清楚。为了在体内表征SR-BI介导的HDL代谢过程，我们通过腺病毒载体基因转移在载脂蛋白A-I（apoA-I）基因敲除小鼠的肝脏中高水平表达该受体，然后向小鼠注射一剂用¹²⁵I-二乳糖醇酪胺标记的人HDL₂。通过非变性凝胶电泳测量，从过表达SR-BI的apoA-I基因敲除小鼠中回收的HDL明显小于从对照小鼠中回收的HDL。当将这些HDL“残余物”注射到C57BL/6小鼠体内时，它们迅速转化为HDL₂大小的脂蛋白颗粒，并以与HDL₂相似的速率从血浆中清除。在培养细胞实验中，HDL残余物不会刺激ATP结合盒转运蛋白A1依赖性胆固醇流出。当在体外与小鼠血浆混合时，HDL残余物迅速转化为更大的HDL颗粒。这些研究确定了HDL代谢中一条先前定义不明确的途径，即SR-BI产生小而致密的HDL颗粒，这些颗粒在血浆中迅速重塑。这种重塑途径可能代表了一个在决定apoA-I分解代谢速率和HDL介导的逆向胆固醇转运中起重要作用的过程。
