Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner
Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner
复制标题
DOI：
10.1194/jlr.m600145-jlr200
复制
发表时间：
2006-07-01
影响因子：
6.5
通讯作者：
Yokoyama, Shinji
中科院分区：
文献类型：
--
作者：
Abe-Dohmae, Sumiko;Kato, Koichi H.;Yokoyama, Shinji
血清淀粉样蛋白A（SAA）是一种两亲性螺旋蛋白，在各种病理条件下，如急性或慢性炎症中与血浆HDL相关。细胞的脂质释放和生成HDL的这种蛋白质进行了研究，与载脂蛋白A-I（apoA-I）的反应和几种类型的细胞，出现了各种具体的档案的胆固醇和磷脂释放的比较。SAA介导的细胞脂质释放与apoA-I相同。肝X受体/维甲酸X受体激动剂上调细胞ABCA 1蛋白导致apoA-I和SAA增加细胞脂质释放。SAA与稳定表达人ABCA 1（293/2c）或ABCA 7（293/6c）的HEK 293衍生克隆反应，以与apoA-I类似的方式产生含胆固醇的HDL。二丁酰环腺苷酸和佛波醇12-肉豆蔻酸酯13-乙酸酯，区分apoA-I介导的细胞脂质释放之间的293/2c和293/6c，也表现出相同的差异效应SAA介导的反应。没有证据表明SAA的ABCA 1/ABCA 7-独立的脂质释放。HDL的物理化学性质的表征表明，SAA产生的HDL颗粒具有更高的密度，更大的直径，和更慢的电泳迁移率比apoA-I产生的。这些结果表明SAA直接与细胞脂质产生含胆固醇的HDL，并且该反应由ABCA 1和ABCA 7介导。
Serum amyloid A (SAA) is an amphiphilic helical protein that is found associated with plasma HDL in various pathological conditions, such as acute or chronic inflammation. Cellular lipid release and generation of HDL by this protein were investigated, in comparison with the reactions by apolipoprotein A-I (apoA-I) and several types of cells that appear with various specific profiles of cholesterol and phospholipid release. SAA mediated cellular lipid release from these cells with the same profile as apoA-I. Upregulation of cellular ABCA1 protein by liver X receptor/retinoid X receptor agonists resulted in an increase of cellular lipid release by apoA-I and SAA. SAA reacted with the HEK293-derived clones that stably express human ABCA1 (293/2c) or ABCA7 (293/6c) to generate cholesterol-containing HDL in a similar manner to apoA-I. Dibutyryl cyclic AMP and phorbol 12-myristate 13-acetate, which differentiate apoA-I-mediated cellular lipid release between 293/2c and 293/6c, also exhibited the same differential effects on the SAA-mediated reactions. No evidence was found for the ABCA1/ABCA7-independent lipid release by SAA. Characterization of physicochemical properties of the HDL revealed that SAA-generated HDL particles had higher density, larger diameter, and slower electrophoretic mobility than those generated by apoA-I. These results demonstrate that SAA generates cholesterol-containing HDL directly with cellular lipid and that the reaction is mediated by ABCA1 and ABCA7.