Oxidized-low density lipoprotein accumulates cholesterol esters via the PKCα-adipophilin-ACAT1 pathway in RAW264.7 cells

Mol Med Rep. 2015 Sep;12(3):3599-3606. doi: 10.3892/mmr.2015.3864. Epub 2015 May 27.

Abstract

Oxidized low‑density lipoprotein (ox‑LDL) can increase the expression of adipophilin and the accumulation of intracellular lipid droplets. However, the detailed mechanisms remain to be fully elucidated. The present study aimed to investigate the mechanism underlying the effect of ox‑LDL on the expression of adipophilin and the accumulation of intracellular cholesterol esters. The results revealed that ox‑LDL increased the activation of protein kinase C α (PKCα), expression of adipophilin and acyl‑coenzymeA: cholesterol acyltransferse 1 (ACAT1) and increased accumulation of intracellular cholesterol esters. In addition, PKCα siRNA abrogated ox‑LDL‑induced adipophilin, expression of ATAC1 and accumulation of cholesterol esters. Furthermore, ox‑LDL increased the accumulation of intracellular cholesterol esters and expression of ACAT1, and this effect were reversed by transfection with adipophilin siRNA. Taken together, these results demonstrated that ox‑LDL induces the accumulation of cholesterol esters, which is mediated by the PKCα‑adipophilin‑ACAT1 pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Acetyl-CoA C-Acetyltransferase / genetics
  • Acetyl-CoA C-Acetyltransferase / metabolism*
  • Animals
  • Cholesterol Esters / metabolism*
  • Gene Expression Regulation
  • Lipoproteins, LDL / metabolism*
  • Macrophages / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Perilipin-2
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism*
  • RAW 264.7 Cells
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Signal Transduction

Substances

  • Cholesterol Esters
  • Lipoproteins, LDL
  • Membrane Proteins
  • Perilipin-2
  • Plin2 protein, mouse
  • RNA, Small Interfering
  • oxidized low density lipoprotein
  • Acat1 protein, mouse
  • Acetyl-CoA C-Acetyltransferase
  • Protein Kinase C-alpha