title: MCP-1 impacts RCT by repressing ABCA1, ABCG1, and SR-BI through PI3K/Akt posttranslational regulation in HepG2 cells.
abstract: 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.
authors: Department of Cardiology, Sun Yat-sen Memorial Hospital, University of Sun Yat-sen, Guangzhou, China.
authors: Can-Xia
authors: CX
authors: Huang
authors: Yu-Ling
authors: YL
authors: Zhang
authors: Jing-Feng
authors: JF
authors: Wang
authors: Jie-Yu
authors: JY
authors: Jiang
authors: Jin-Lan
authors: JL
authors: Bao
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D053492:Elafin / Q000378:metabolism; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053492:Elafin; C506806:PI3 protein, human; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D051058:Oncogene Protein v-akt
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