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PPARgamma phosphorylation mediated by JNK MAPK: a potential role in macrophage-derived foam cell formation

Ran Yin1, Yu-gang Dong, Hong-liang Li

  • 1Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

Acta Pharmacologica Sinica
|August 23, 2006
PubMed
Abstract

Insights

Oxidized low-density lipoprotein (ox-LDL) triggers macrophage foam cell formation by phosphorylating peroxisome proliferator-activated receptor gamma (PPARgamma) via mitogen-activated protein kinase (MAPK) pathways. This phosphorylation impairs PPARgamma activity, promoting foam cell development.

Area of Science:

  • Cardiovascular Biology
  • Cellular Signaling
  • Atherosclerosis Research

Background:

  • Oxidized low-density lipoprotein (ox-LDL) is implicated in atherosclerosis.
  • Macrophage foam cell formation is a key event in atherogenesis.
  • Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a role in lipid metabolism and inflammation.

Purpose of the Study:

  • To determine if ox-LDL affects PPARgamma activity via phosphorylation in macrophages.
  • To investigate the role of mitogen-activated protein kinase (MAPK) pathways in ox-LDL-induced PPARgamma phosphorylation.
  • To examine the impact of PPARgamma phosphorylation on macrophage foam cell formation.

Main Methods:

  • THP-1 cells were treated with ox-LDL and MAPK inhibitors.
  • Western blot was used to detect PPARgamma and phosphorylated PPARgamma levels.
  • MAPK activity, intracellular cholesterol, and PPARgamma target gene expression were quantified.

Main Results:

  • ox-LDL induced MAPK activation and PPARgamma phosphorylation in a dose-dependent manner.
  • Inhibition of c-Jun N-terminal kinase (JNK) significantly reduced ox-LDL-induced PPARgamma phosphorylation.
  • PPARgamma phosphorylation correlated with increased foam cell formation.

Conclusions:

  • ox-LDL modulates PPARgamma activity through MAPK-mediated phosphorylation, independent of ligand binding.
  • MAPK-activated PPARgamma phosphorylation promotes foam cell formation in macrophages exposed to ox-LDL.
  • Targeting MAPK or PPARgamma phosphorylation may offer therapeutic strategies for atherosclerosis.

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