Scavenger receptor class B, type I-mediated [3H]cholesterol efflux to high and low density lipoproteins is dependent on lipoprotein binding to the receptor
Scavenger receptor class B, type I-mediated [3H]cholesterol efflux to high and low density lipoproteins is dependent on lipoprotein binding to the receptor
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DOI：
10.1074/jbc.275.39.29993
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发表时间：
2000-09-29
影响因子：
4.8
通讯作者：
Krieger, M
中科院分区：
文献类型：
--
作者：
Gu, XJ;Kozarsky, K;Krieger, M
鼠清道夫受体B类I型（mSR-BI）是高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和乙酰化LDL（AcLDL）的受体。它介导脂蛋白脂质的选择性吸收并刺激[H-3]胆固醇流出至脂蛋白。提出SR-BI介导的[H-3]胆固醇流出不依赖于配体结合。在本研究中，使用抗mSR-BI抗体KKB-1和两种具有改变的配体结合特性的mSR-BI突变体，我们证明了SR-BI介导的[H-3]胆固醇流出至脂蛋白与受体的配体结合和脂质摄取活性相关。KKB-1抗体阻断脂蛋白结合而基本上不改变胆固醇氧化酶可接近的细胞[H-3]胆固醇，也阻断[H-3]胆固醇流出到HDL和LDL。其中一个SR-BI突变体在402和418位（Q402 R/Q418 R）处具有谷氨酰胺对丙氨酸的双取代，其表现出高水平的LDL结合和从LDL的脂质摄取，但丧失了大部分相应的HDL受体活性。该突变体可以介导[H-3]胆固醇有效流出到LDL，但不能流出到HDL。另一个突变体M158 R，在158位用精氨酸代替甲硫氨酸，表现出降低的HDL和LDL受体活性，但明显正常的AcLDL受体活性。该突变体可介导[H-3]胆固醇有效流出至AcLDL，但不能流出至HDL或LDL。这些结果表明，SR-BI刺激的[H-3]胆固醇流出脂蛋白严重依赖于配体结合这种受体，并提高了选择性脂质摄取和[H-3]胆固醇流出的机制可能密切相关的可能性。
The murine scavenger receptor class B, type I (mSR-BI) is a receptor for high density lipoprotein (HDL), low density lipoprotein (LDL), and acetylated LDL (AcLDL). It mediates selective uptake of lipoprotein lipid and stimulates efflux of [H-3]cholesterol to lipoproteins. SR-BI-mediated [H-3]cholesterol efflux was proposed to be independent of ligand binding. In this study, using anti-mSR-BI antibody KKB-1 and two mSR-BI mutants with altered ligand binding properties, we demonstrated that SR-BI-mediated [H-3]cholesterol efflux to lipoproteins was correlated with ligand binding and lipid uptake activities of the receptor. The KKB-1 antibody, which blocked lipoprotein binding without substantially altering the cholesterol oxidase-accessible cellular [H-3]cholesterol, also blocked [H-3]cholesterol efflux to HDL and LDL. One of the SR-BI mutants, which has a double substitution of arginines for glutamines at positions 402 and 418 (Q402R/Q418R), exhibited a high level of LDL binding and lipid uptake from LDL, but lost most of the corresponding HDL receptor activity. This mutant could mediate efficient [H-3]cholesterol efflux to LDL, but not to HDL. Another mutant, M158R, with an arginine in place of methionine at position 158, exhibited reduced HDL and LDL receptor activities, but apparently normal AcLDL receptor activity. This mutant could mediate efficient [H-3]cholesterol efflux to AcLDL, but not to HDL or LDL. These results suggest that SR-BI-stimulated [H-3]cholesterol efflux to lipoproteins critically depends on ligand binding to this receptor and raise the possibility that the mechanisms of selective lipid uptake and [H-3]cholesterol efflux may be intimately related.