Journal
JOURNAL OF LIPID RESEARCH
Volume 54, Issue 5, Pages 1231-1240Publisher
ELSEVIER
DOI: 10.1194/jlr.M032482
Keywords
monocyte chemoattractant protein-1; reverse cholesterol transport; HepG2 cells; high density lipoprotein; phosphoinositide 3-kinase/Akt pathway; ATP binding cassette A1; ATP binding cassette G1; scavenger receptor-class B type I
Categories
Funding
- Natural Science Foundation of China [81070182]
- Natural Science Foundation of Guangdong Province [10151008901000224]
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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.-Huang, C-X., Y-L. Zhang, J-F. Wang, J-Y. Jiang, and J-L. Bao. MCP-1 impacts RCT by repressing ABCA1, ABCG1, and SR-BI through PI3K/Akt posttranslational regulation in HepG2 cells. J. Lipid Res. 54: 1231-1240.
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