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Endoplasmic reticulum stress is involved in acetylated low-density lipoprotein induced apoptosis in THP-1

Jian-ling Tao1, Xiong-zhong Ruan, Hang Li

  • 1Division of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

Chinese Medical Journal
|September 29, 2009
PubMed

Insights

Acetyl-low-density lipoprotein (AcLDL) induces apoptosis in macrophages by causing endoplasmic reticulum (ER) stress due to free cholesterol accumulation. This finding is crucial for understanding atherosclerosis in chronic kidney disease patients.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Cardiovascular disease is a significant cause of mortality in chronic kidney disease patients.
  • Macrophage apoptosis in atherosclerosis contributes to plaque destabilization.
  • Endoplasmic reticulum (ER) stress from free cholesterol accumulation induces apoptosis in peritoneal macrophages.

Purpose of the Study:

  • To investigate if acetylated low-density lipoprotein (AcLDL) induces apoptosis in THP-1 macrophages.
  • To elucidate the underlying mechanisms of AcLDL-induced apoptosis, focusing on ER stress and cholesterol accumulation.

Main Methods:

  • THP-1 cells were differentiated using phorbol 12-myristate 13-acetate (PMA).
  • AcLDL uptake was visualized using confocal microscopy.
  • Apoptosis was detected using Hoechst 33258 stain and caspase 3,7 assay.
  • Intracellular free cholesterol (FC) and cholesterol ester (CE) levels were quantified using High-Performance Liquid Chromatography (HPLC).
  • Protein and mRNA levels were analyzed via Western blotting and real-time PCR, respectively.

Main Results:

  • AcLDL uptake increased with longer PMA differentiation.
  • AcLDL induced time- and dose-dependent apoptosis in THP-1 macrophages.
  • AcLDL exposure significantly increased caspase 3,7 activity, FC and CE mass, and ER free cholesterol.
  • AcLDL upregulated C/EBP homologous protein and downregulated Bcl-2 at both protein and mRNA levels.

Conclusions:

  • Endoplasmic reticulum (ER) stress is implicated in AcLDL-induced apoptosis.
  • Free cholesterol accumulation in the ER is a key mechanism in AcLDL-induced macrophage apoptosis.
Abstract

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