Abstract
Aim:
To investigate whether oxidized low-density lipoprotein (ox-LDL) modulates peroxisome proliferator-activated receptor γ (PPARγ) activity through phosphorylation in macrophages, and the effect of PPARγ phosphorylation on macrophages-derived foam cell formation.
Methods:
After exposing the cultured THP-1 cells to ox-LDL in the presence or absence of different mitogen-activated protein kinase (MAPK) inhibitors, PPARγ and phosphorylated PPARγ protein levels were detected by Western blot. MAPK activity was analyzed using MAP Kinase Assay Kit. Intracellular cholesterol accumulation was assessed by Oil red O staining and cholesterol oxidase enzymatic method. The mRNA level of PPARγ target gene was determined by reverse transcription-polymerase chain reaction (RT-PCR).
Results:
ox-LDL evaluated PPARγ phosphorylation status and subsequently decreased PPARγ target gene expression in a dose-dependent manner. ox-LDL also induced MAPK activation. Treatment of THP-1 cells with c-Jun N-terminal kinase-, but not p38- or extracellular signal-regulated kinase-MAPK inhibitor, significantly suppressed PPARγ phosphorylation induced by ox-LDL, which in turn inhibited foam cell formation.
Conclusion:
In addition to its ligand-dependent activation, ox-LDL modulates PPARγ activity through phosphorylation, which is mediated by MAPK activation. PPARγ phosphorylation mediated by MAPK facilitates foam cell formation from macrophages exposed to ox-LDL.
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Project supported by the Natural Science Foundation of Guangdong Province, China (2003).
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Yin, R., Dong, Yg. & Li, Hl. PPARγ phosphorylation mediated by JNK MAPK: a potential role in macrophage-derived foam cell formation. Acta Pharmacol Sin 27, 1146–1152 (2006). https://doi.org/10.1111/j.1745-7254.2006.00359.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00359.x
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