B类I型清道夫受体与胆固醇的双向转运

B类I型清道夫受体是一种细胞膜的糖蛋白,具有广泛的配基识别谱,在多种组织中高度表达.它是一种高密度脂蛋白(HDL)的高亲和力受体,在细胞水平上介导高密度脂蛋白和低密度脂蛋白选择性摄取胆固醇酯.在介导游离胆固醇的双向转运,参与动脉壁胆固醇的清除中起着重要作用.     

稳定表达A类I型清道夫受体的HEK293细胞系的建立

目的建立稳定表达A类I型清道夫受体真核表达载体的人胚肾细胞——HEK293细胞系。方法构建pRc/CMV-A类I型清道夫受体真核表达载体,应用脂质体介导的转染技术将该质粒导入HEK293细胞,再用G418筛选稳定的细胞表达系。真核细胞中A类I型清道夫受体的表达分别用逆转录聚合酶链反应与W     

B类I型清道夫受体过表达对J774细胞胆固醇转运以及肿瘤坏死因子α表达的影响

目的通过构建人B类Ⅰ型清道夫受体真核表达载体、使细胞瞬时过表达B类Ⅰ型清道夫受体，观察其对肿瘤坏死因子（tmnor neerosis factor,TNF）α和单核细胞趋化因子1（monocyte chemoattractant protin MCPI）表达的影响，初步探讨单核-巨噬细胞B类Ⅰ型清道夫受体抗动脉粥样硬化的作用机制，     

B类Ⅰ型清道夫受体与胆固醇的双向转运

B类Ⅰ型清道夫受体是一种细胞膜的糖蛋白,具有广泛的配基识别谱,在多种组织中高度表达。它是一种高密度脂蛋白(HDL)的高亲和力受体,在细胞水平上介导高密度脂蛋白和低密度脂蛋白选择性摄取胆固醇酯。在介导游离胆固醇的双向转运,参与动脉壁胆固醇的清除中起着重要作用。     

稳定表达A类I型清道夫受体的HEK293细胞系的建立

目的建立稳定表达A类Ⅰ型清道夫受体真核表达载体的人胚肾细胞——HEK293细胞系。方法构建pRc／CMV-A类Ⅰ型清道夫受体真核表达载体，应用脂质体介导的转染技术将该质粒导入HEK293细胞，再用G418筛选稳定的细胞表达系。真核细胞中A类I型清道夫受体的表达分别用逆转录聚合酶链反应与Westem blot方法检测。     

清道夫受体BI与动脉粥样硬化

清道夫受体B族I型(SR-BI)是细胞膜上首个被定义为高密度脂蛋白(HDL)受体的糖蛋白,其介导细胞选择性摄取高密度脂蛋白胆固醇(HDLC),影响细胞胆固醇平衡、炎症表型。肝脏SR-BI在胆固醇逆向转运中扮演重要角色,而与HDL的代谢及其抗动脉粥样硬化(As)作用密切相关,并且已发现人类存在SR-BI基因多态性。本文重点从SR-BI结构、功能、调节及其对As的作用进行综述。     

低层流切应力对内皮细胞表面B族Ⅰ型清道夫受体表达的影响

目的 研究低层流切应力作用下,血管内皮细胞表面保护性脂蛋白高密度脂蛋白的特异性受体B族Ⅰ型清道夫受体的表达水平,探讨切应力对内皮细胞表面B族Ⅰ型清道夫受体表达的影响在动脉粥样硬化发生中的可能作用.方法 无菌条件下取健康产妇剖宫产分娩的胎儿新鲜脐带培养人脐静脉内皮细胞,选择2～4代的细胞用于实验,将内皮细胞种植于载玻片上培养,待细胞长满汇合后放入流室系统中.实验分为实验组和对照组,选择静态条件下未施加切应力组为对照组,实验组为低切应力组(4.2 dyne/cm~2).切应力加载时间为1 h、2 h、4 h和8 h.作用完成后行半定量RT-PCR测定B族Ⅰ型清道夫受体的表达.结果 在层流低切应力(4.2 dyne/cm~2)刺激后,B族Ⅰ型清道夫受体表达随时间延长明显减弱,在8 h达低谷,在电泳图上几乎不显现.结论 高密度脂蛋白的特异性受体B族Ⅰ型清道夫受体在低切应力(4.2 dyne/cm~2)作用下表达减弱;低切应力可能通过下调B族Ⅰ型清道夫受体的表达,降低胆固醇的逆转运,促进血管动脉粥样硬化的发生.     

与动脉粥样硬化密切相关的清道夫受体

清道夫受体是一类结构多样化的糖蛋白受体，具有广泛的配体谱和功能。已知清道夫受体与动脉粥样硬化、宿主防御、细胞粘附、细胞增殖以及细胞凋亡等均有不同程度的关系。已经发现的清道夫受体分为A、B、C、D、E、F、G几大类型，其中清道夫受体A型（SR-AI，SR-AII）和清道夫受体B型（SR-BI，CD36）研究的较多，并且已被证明与动脉粥样硬化密切相关。SR-A和CD36被认为是主要的致动脉粥样硬化受体；而SR-BI作为高密度脂蛋白受体参与胆固醇酯的逆转运过程，是重要的抗动脉粥样硬化的受体。本文主要综述这几类清道夫受体的结构、功能、信号转导、表达调控以及以它们为靶点进行的药物研究。     

脑卒中患者B族Ⅰ型清道夫受体基因G4A多态性与血脂水平的关系

目的探讨B族Ⅰ型清道夫受体基因G4A多态性与脑卒中患者血脂水平的关系。方法采用聚合酶链反应限制片长多态性技术检测149例动脉粥样硬化性脑梗死患者、141例脑出血患者和120例健康对照者B族Ⅰ型清道夫受体基因G4A多态的分布,并测定三组研究对象的血脂水平。结果动脉粥样硬化性脑梗死组和脑出血组B族Ⅰ型清道夫受体G4A GA AA基因型亚组高密度脂蛋白胆固醇水平显著高于同组GG基因型亚组(P<0.05),低密度脂蛋白胆固醇水平显著低于同组GG基因型亚组(P<0.05)。对照组B族Ⅰ型清道夫受体G4A GA AA基因型亚组高密度脂蛋白胆固醇水平显著高于GG基因型亚组,而低密度脂蛋白胆固醇和总胆固醇水平显著低于同组GG基因型亚组(P<0.05)。男性动脉粥样硬化性脑梗死组和男性脑出血组GA AA基因型亚组高密度脂蛋白胆固醇水平显著高于同组GG基因型亚组,低密度脂蛋白胆固醇水平显著低于同组GG基因型亚组。女性动脉粥样硬化性脑梗死组和女性脑出血组不同基因型亚组体质指数和血脂水平差异无显著性。结论B族Ⅰ型清道夫受体基因G4A位点A等位基因可能与男性高密度脂蛋白和低密脂蛋白代谢有关。     

B类清道夫受体I与脂质的选择性吸收

B类清道夫受体I(scavenger receptor class B type I,SR-BI)是最先被确定的高密度脂蛋白(HDL)受体。它与CD36一样属于多配体受体,能够直接与多种蛋白质和脂质发生作用。SR-BI可以介导细胞膜上脂质的双向转运,即脂质选择性摄取和胆固醇的流出。脂质的选择性吸收与传统意义上的低密度脂蛋白(LDL)受体所介导的内吞明显不同,选择性吸收是指脂蛋白中的脂质被选择性吸收,而脂蛋白成分可释放再利用的过程[1],LDL受体介导的是脂蛋白与脂质均被内吞入细胞的过程。本文就SR-BI在脂质选择性吸收中的作用及其调节作一综述。     

Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol

Scavenger receptor BI (SR-BI) is a cell surface receptor that binds high density lipoproteins (HDL) and mediates selective uptake of HDL cholesteryl esters (CE) in transfected cells. To address the physiological role of SR-BI in HDL cholesterol homeostasis, mice were generated bearing an SR-BI promoter mutation that resulted in decreased expression of the receptor in homozygous mutant (designated SR-BI att) mice. Hepatic expression of the receptor was reduced by 53% with a corresponding increase in total plasma cholesterol levels of 50–70% in SR-BI att mice, attributable almost exclusively to elevated plasma HDL. In addition to increased HDL-CE, HDL phospholipids and apo A-1 levels were elevated, and there was an increase in HDL particle size in mutant mice. Metabolic studies using HDL bearing nondegradable radiolabels in both the protein and lipid components demonstrated that reducing hepatic SR-BI expression by half was associated with a decrease of 47% in selective uptake of CE by the liver, and a corresponding reduction of 53% in selective removal of HDL-CE from plasma. Taken together, these findings strongly support a pivotal role for hepatic SR-BI expression in regulating plasma HDL levels and indicate that SR-BI is the major molecule mediating selective CE uptake by the liver. The inverse correlation between plasma HDL levels and atherosclerosis further suggests that SR-BI may influence the development of coronary artery disease.     

Scavenger receptor class B, type I: a promising immunotherapy target

Scavenger receptor class B, type I (SR-BI) is a crucial molecule in lipid metabolism, since the interaction of high-density lipoproteins (HDLs) with SR-BI is involved in reverse cholesterol transport and cholesterol efflux. Recent findings also underscore a critical role of SR-BI in antimicrobial and immune responses. SR-BI is not only highly expressed in liver and steroidogenic glands, but also in endothelial cells, macrophages and dendritic cells. SR-BI mainly mediates anti-inflammatory responses, which may be altered by dysfunctional HDLs produced in several diseases. Moreover, SR-BI has been involved in the capture and cross-presentation of antigens from viruses, bacteria and parasites. It thus works as a pattern-recognition receptor that interacts with both damage-associated molecular patterns and pathogen-associated molecular patterns. These new findings in the microbiology and immunology fields present SR-BI as an unexplored therapeutic target that warrants further basic and applied research.     

Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology.

The high density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B type I) mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. As a consequence, SR-BI can influence plasma HDL cholesterol levels, HDL structure, biliary cholesterol concentrations, and the uptake, storage, and utilization of cholesterol by steroid hormone-producing cells. Here we used homozygous null SR-BI knockout mice to show that SR-BI is required for maintaining normal biliary cholesterol levels, oocyte development, and female fertility. We also used SR-BI/apolipoprotein E double homozygous knockout mice to show that SR-BI can protect against early-onset atherosclerosis. Although the mechanisms underlying the effects of SR-BI loss on reproduction and atherosclerosis have not been established, potential causes include changes in (i) plasma lipoprotein levels and/or structure, (ii) cholesterol flux into or out of peripheral tissues (ovary, aortic wall), and (iii) reverse cholesterol transport, as indicated by the significant reduction of gallbladder bile cholesterol levels in SR-BI and SR-BI/apolipoprotein E double knockout mice relative to controls. If SR-BI has similar activities in humans, it may become an attractive target for therapeutic intervention in a variety of diseases.     

Identification and expression of scavenger receptor SR-BI in endothelial cells and smooth muscle cells of rat aorta in vitro and in vivo

In this study, we used immunoelectron microscopy to investigate the subcellular localization of scavenger receptor class B type I (SR-BI) in the arterial walls of rats. The expression of SR-BI in cultured endothelial and smooth muscle cells of rat aorta after exposure to high-density lipoprotein (HDL) was also investigated by immunofluorescence microscopy and immunoblotting analysis. A peptide containing residues 495-509 from mouse SR-BI (mSR-BI) plus an NH2-terminal cysteine was coupled to hemocyanin to generate mSR-BI antiserum in rabbits. Reactivity of antiserum against the synthetic peptides was confirmed with an enzyme-linked immunosorbent assay (ELISA). The results showed that SR-BI was specifically localized on the surface of the endothelial cells and smooth muscle cells. SR-BI was also observed in the cytoplasm of smooth muscle cells. Immunoblotting analysis indicated that SR-BI was expressed in the cell membrane. The levels of SR-BI increased gradually from 1 to 3 h and decreased at 24 and 48 h after cholesterol-loaded cells were incubated in the culture medium containing HDL. We conclude that SR-BI, a functional receptor for HDL, is expressed in the aortic endothelial cells as well as in smooth muscle cells. This receptor also responds to the presence of HDL in the culture medium.     

SR-BI-mediated HDL cholesteryl ester delivery in the adrenal gland

In adrenocortical cells, scavenger receptor class B, type I (SR-BI) is localized in specialized plasma membrane compartments, called microvillar channels, that retain high density lipoprotein particles (HDL) and are sites for the selective uptake of cholesteryl esters (CE). Formation of microvillar channels is regulated by adrenocorticotropic hormone (ACTH) and requires SR-BI expression. Subsequent to SR-BI-mediated delivery to the plasma membrane, HDL-CE is metabolized to free cholesterol by hormone sensitive lipase and transported to the mitochondria for steroid synthesis via START domain proteins. The relevance of SR-BI to adrenal steroidogenesis is evident by the impairment of glucocorticoid-mediated stress response in the absence of SR-BI-mediated HDL-CE uptake in mice. On the molecular level, SR-BI mediates HDL-CE selective uptake by forming a hydrophobic channel. In addition, SR-BI facilitates bi-directional flux of cholesterol by modifying the phospholipid content of the plasma membrane. SR-BI most likely accomplishes these functions by forming homo-oligomers in the plasma membrane. Examination of SR-BI oligomerization using fluorescence resonance energy transfer spectroscopy revealed that SR-BI multimerizes via its C-terminal region. Overall, SR-BI is the cell surface receptor responsible for selective uptake of lipoprotein cholesterol and its ultimate delivery to sites of hormone synthesis in steroidogenic tissues.