PMID- 23402987
OWN - NLM
STAT- MEDLINE
DCOM- 20131104
LR  - 20211021
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 54
IP  - 5
DP  - 2013 May
TI  - MCP-1 impacts RCT by repressing ABCA1, ABCG1, and SR-BI through PI3K/Akt 
      posttranslational regulation in HepG2 cells.
PG  - 1231-40
LID - 10.1194/jlr.M032482 [doi]
AB  - 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.
FAU - Huang, Can-Xia
AU  - Huang CX
AD  - Department of Cardiology, Sun Yat-sen Memorial Hospital, University of Sun 
      Yat-sen, Guangzhou, China.
FAU - Zhang, Yu-Ling
AU  - Zhang YL
FAU - Wang, Jing-Feng
AU  - Wang JF
FAU - Jiang, Jie-Yu
AU  - Jiang JY
FAU - Bao, Jin-Lan
AU  - Bao JL
LA  - eng
PT  - Journal Article
DEP - 20130212
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (ABCA1 protein, human)
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Elafin)
RN  - 0 (PI3 protein, human)
RN  - 0 (SCARB1 protein, human)
RN  - 0 (Scavenger Receptors, Class B)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
SB  - IM
MH  - ATP Binding Cassette Transporter 1
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/*genetics/metabolism
MH  - Atherosclerosis/*genetics/pathology
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Cholesterol/metabolism
MH  - Elafin/metabolism
MH  - Gene Expression Regulation
MH  - Hep G2 Cells
MH  - Humans
MH  - Oncogene Protein v-akt/metabolism
MH  - Protein Processing, Post-Translational
MH  - Scavenger Receptors, Class B/*genetics/metabolism
MH  - Signal Transduction
PMC - PMC3622320
EDAT- 2013/02/14 06:00
MHDA- 2013/11/05 06:00
PMCR- 2014/05/01
CRDT- 2013/02/14 06:00
PHST- 2013/02/14 06:00 [entrez]
PHST- 2013/02/14 06:00 [pubmed]
PHST- 2013/11/05 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - S0022-2275(20)42162-5 [pii]
AID - m032482 [pii]
AID - 10.1194/jlr.M032482 [doi]
PST - ppublish
SO  - J Lipid Res. 2013 May;54(5):1231-40. doi: 10.1194/jlr.M032482. Epub 2013 Feb 12.