MCP-1 impacts RCT by repressing ABCA1, ABCG1, and SR-BI through PI3K/Akt posttranslational regulation in HepG2 cells[S]

Journal of Lipid Research

卷:54

Jie-Yu Jiang¹  Yu-Ling Zhang²  Jin-Lan Bao²  Can-Xia Huang³  Jing-Feng Wang⁴ 

[1] Department of Cardiology, Sun Yat-sen Memorial Hospital, University of Sun Yat-sen, Guangzhou, China 510120;

[2] Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Sun Yat-sen Memorial Hospital, University of Sun Yat-sen, Guangzhou, China 510120;

[3] To whom correspondence should be addressed [e-mail];

关键词: monocyte chemoattractant protein -1;    reverse cholesterol transport;    HepG2 cells;    high density lipoprotein;    phosphoinositide 3-kinase/Akt pathway;    ATP binding cassette A1;   

DOI  :  

来源: DOAJ

【 摘 要 】

Monocyte chemoattractant protein-1 (MCP-1) plays crucial roles at multiple stages of atherosclerosis. We hypothesized that MCP-1 might impair the reverse cholesterol transport (RCT) capacity of HepG2 cells by decreasing the cell-surface protein expression of ATP binding cassette A1 (ABCA1), ATP binding cassette G1 (ABCG1), and scavenger receptor class B type I (SR-BI). MCP-1 reduced the total protein and mRNA levels of ABCA1 and SR-BI, but not of ABCG1. MCP-1 decreased the cell-surface protein expression of ABCA1, ABCG1, and SR-BI in dose-dependent and time-dependent manners, as measured using cell-surface biotinylation. We further studied the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase Akt pathway in regulating receptor trafficking. Both the translation and transcription of ABCA1, ABCG1, and SR-BI were not found to be regulated by the PI3K/Akt pathway. However, the cell-surface protein expression of ABCA1, ABCG1, and SR-BI could be regulated by PI3K activity, and PI3K activation corrected the MCP-1-induced decreases in the cell-surface protein expression of ABCA1, ABCG1, and SR-BI. Moreover, we found that MCP-1 decreased the lipid uptake by HepG2 cells and the ABCA1-mediated cholesterol efflux to apoA-I, which could be reversed by PI3K activation. Our data suggest that MCP-1 impairs RCT activity in HepG2 cells by a PI3K/Akt-mediated posttranslational regulation of ABCA1, ABCG1, and SR-BI cell-surface expression.

【 授权许可】

Unknown