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

Can-Xia Huang1, Yu-Ling Zhang, Jing-Feng Wang

  • 1Department of Cardiology, Sun Yat-sen Memorial Hospital, University of Sun Yat-sen, Guangzhou, China.

Journal of Lipid Research
|February 14, 2013
PubMed

Insights

Monocyte chemoattractant protein-1 (MCP-1) reduces cell-surface expression of key cholesterol transporters, impairing reverse cholesterol transport. This effect is mediated by the PI3K/Akt pathway, suggesting a therapeutic target for atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Cellular Metabolism
  • Molecular Medicine

Background:

  • Atherosclerosis involves complex cellular processes, including cholesterol homeostasis.
  • Monocyte chemoattractant protein-1 (MCP-1) is implicated in atherosclerotic plaque development.
  • Reverse cholesterol transport (RCT) is critical for preventing cholesterol accumulation in arteries.

Purpose of the Study:

  • To investigate the impact of MCP-1 on RCT in HepG2 cells.
  • To determine if MCP-1 affects the cell-surface expression of cholesterol transporters ABCA1, ABCG1, and SR-BI.
  • To elucidate the role of the PI3K/Akt pathway in MCP-1-mediated regulation of these transporters.

Main Methods:

  • HepG2 cells were treated with MCP-1.
  • Cell-surface protein expression of ABCA1, ABCG1, and SR-BI was measured using biotinylation assays.
  • Total protein and mRNA levels were assessed.
  • The involvement of the PI3K/Akt pathway was investigated using pathway inhibitors and activators.
  • Lipid uptake and cholesterol efflux assays were performed.

Main Results:

  • MCP-1 reduced total protein and mRNA of ABCA1 and SR-BI, but not ABCG1.
  • MCP-1 significantly decreased cell-surface expression of ABCA1, ABCG1, and SR-BI in a dose- and time-dependent manner.
  • The PI3K/Akt pathway did not regulate the transcription or translation of these transporters.
  • PI3K activation reversed MCP-1-induced reductions in cell-surface transporter expression.
  • MCP-1 impaired lipid uptake and ABCA1-mediated cholesterol efflux, which PI3K activation could restore.

Conclusions:

  • MCP-1 impairs RCT in HepG2 cells.
  • This impairment is linked to decreased cell-surface expression of ABCA1, ABCG1, and SR-BI.
  • The mechanism involves PI3K/Akt-mediated posttranslational regulation of these transporters.
  • Targeting the PI3K/Akt pathway may offer a strategy to improve RCT in atherosclerosis.

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