Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake
Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake
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DOI：
10.1074/jbc.m411555200
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发表时间：
2005-01-28
影响因子：
4.8
通讯作者：
van der Westhuyzen, DR
中科院分区：
文献类型：
--
作者：
Cai, L;de Beer, MC;van der Westhuyzen, DR
血清淀粉样蛋白 A 是一种急性时相蛋白，主要作为高密度脂蛋白 (HDL) 的载脂蛋白在血浆中携带。在本研究中，我们研究了 SAA 是否是 HDL 受体、B 型清道夫受体 I 型 (SR-BI) 的配体，以及 SAA 如何影响 SR-BI 介导的 HDL 结合和选择性胆固醇酯摄取。使用表达 SR-BI 的中国仓鼠卵巢细胞进行的研究表明，I-125 标记的 SAA（无论是无脂形式还是重组 HDL 颗粒）都可作为 SR-BI 的高亲和力配体。 SAA 还与肝细胞系 HepG2 具有高亲和力。荧光共聚焦显微镜显示 Alexa 标记的 SAA 以 SR-BI 依赖性方式被细胞内化。为了评估SAA与HDL的关联如何影响HDL与SR-BI的相互作用，通过腺病毒基因转移从过度表达SAA的小鼠中分离出含有SAA的HDL。 HDL 上的 SAA 对 HDL 与 SR-BI 的结合几乎没有影响，但减少了 (30-50%) 选择性胆固醇酯摄取。与无脂 apoA-1 不同，无脂 SAA 是 SR-BI 依赖性结合和 HDL 选择性胆固醇酯摄取的有效抑制剂。我们得出的结论是，SR-BI 通过其与 SAA 相互作用并内化 SAA 的能力，在 SAA 代谢中发挥关键作用，此外，SAA 通过其对 SR-BI 介导的选择性脂质摄取的抑制作用影响 HDL 胆固醇代谢。
Serum amyloid A is an acute phase protein that is carried in the plasma largely as an apolipoprotein of high density lipoprotein (HDL). In this study we investigated whether SAA is a ligand for the HDL receptor, scavenger receptor class B type I (SR-BI), and how SAA may influence SR-BI-mediated HDL binding and selective cholesteryl ester uptake. Studies using Chinese hamster ovary cells expressing SR-BI showed that I-125- labeled SAA, both in lipid-free form and in reconstituted HDL particles, functions as a high affinity ligand for SR-BI. SAA also bound with high affinity to the hepatocyte cell line, HepG2. Alexa-labeled SAA was shown by fluorescence confocal microscopy to be internalized by cells in a SR-BI-dependent manner. To assess how SAA association with HDL influences HDL interaction with SR-BI, SAA-containing HDL was isolated from mice overexpressing SAA through adenoviral gene transfer. SAA presence on HDL had little effect on HDL binding to SR-BI but decreased (30-50%) selective cholesteryl ester uptake. Lipid-free SAA, unlike lipid-free apoA-1, was an effective inhibitor of both SR-BI-dependent binding and selective cholesteryl ester uptake of HDL. We have concluded that SR-BI plays a key role in SAA metabolism through its ability to interact with and internalize SAA and, further, that SAA influences HDL cholesterol metabolism through its inhibitory effects on SR-BI-mediated selective lipid uptake.