ATP结合盒转运子A1对巨噬细胞载脂蛋白E分泌的调节作用

Regulation of ATP-binding acssette transporter A1 onapolipoprotein E secretion from macrophages

目的 :研究ABC转运子 (ABC)A1对巨噬细胞载脂蛋白E(apoE)的分泌是否具有调节作用。方法 :利用佛波酯刺激人单核细胞系THP - 1细胞分化 ;分别将ABCA1表达的激动剂 8-Br -cAMP、抑制剂格列苯脲和针对ABCA1mRNA的特异性反义寡核苷酸与分化后的THP - 1巨噬细胞或巨噬细胞泡沫细胞一起孵育 ,通过酶联免疫吸附试验和Northernblot检测其对细胞apoE的产生、分泌以及apoE基因表达的影响。结果 :在孵育 8h时 ,8-Br-cAMP可使THP - 1巨噬细胞apoE分泌增加 (P <0 0 5 ) ,而格列苯脲和针对ABCA1mRNA的反义寡核苷酸则明显减少THP - 1巨噬细胞和巨噬细胞泡沫细胞的apoE分泌 (P <0 0 1)。同时这些调节剂均不改变THP1巨噬细胞内apoE含量和apoEmRNA表达水平。结论 :ABCA1促进巨噬细胞和巨噬细胞泡沫细胞apoE的分泌 。

AIM: To investigate the regulatory effect of the adenosine triphosphate binding cassette transporter A1 (ABCA1) on apolipoprotein E secretion from human THP1 macrophages.METHODS: Differentiation of THP1 macrophages from monocytes was stimulated with phorbol 12-myristate 13-acetate. The macrophages then were incubated with factors which regulate ABCA1 expression. After periods of incubation, apo E secreted in the medium and synthesized in the cell was determined with ELISA, and apo E mRNA espression was detected with Northern blot.RESULTS: An increase in apo E secretion from THP1 macrophages was observed by 8 h of incubation with 8-Br-cAMP, an activator of ABCA1 expression (P<0.05). Glyburide, a putative ABCA1 inhibitor, and antisense oligonucleotides specifically against ABCA1 mRNA remarkably decreased apo E secretion from both THP1 macrophages and macrophage foam cells (P<0.01,respectively). Neither apo E mRNA expression nor intracellular apo E level in THP1 macrophages was changed by inhibition of ABCA1.CONCLUSION: ABCA1 may promote the secretion of apo E from macrophages and macrophage foam cells and the effect may occur at the level of post-translation. The present results reveal a new aspect underlying antiatherogenic properties of ABCA1. [