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Aim:To investigate whether oxidized low-density lipoprotein(ox-LDL)modulatesperoxisome proliferator-activated receptorγ(PPARγ)activity through phosphory-lation in macrophages,and the effect of PPARγ phosphorylation on macroph-ages-derived foam cell formation.Methods:After exposing the cultured THP-1cells to ox-LDL in the presence or absence of different mitogen-activated proteinkinase(MAPK)inhibitors,PPARγ and phosphorylated PPARγ protein levels weredetected by Western blot.MAPK activity was analyzed using MAP Kinase As-say Kit.Intracellular cholesterol accumulation was assessed by Oil red O stainingand cholesterol oxidase enzymatic method.The mRNA level of PPARγtarget genewas determined by reverse transcription-polymerase chain reaction(RT-PCR).Results:ox-LDL evaluated PPARγ phosphorylation status and subsequently de-creased PPARγ target gene expression in a dose-dependent manner,ox-LDL alsoinduced MAPK activation.Treatment of THP- 1 cells with c-Jun N-terminal kinase-,but not p38- or extracellular signal-regulated kinase-MAPK inhibitor,significantlysuppressed PPARγ phosphorylation induced by ox-LDL,which in turn inhibitedfoam cell formation.Conclusion:In addition to its ligand-dependent activation,ox-LDL modulates PPARγ activity through phosphorylation,which is mediatedby MAPK activation.PPARγ phosphorylation mediated by MAPK facilitatesfoam cell formation from macrophages exposed to ox-LDL.
Aim: To investigate whether oxidized low-density lipoprotein (ox-LDL) modulates peroxisome proliferator-activated receptor gamma (PPARγ) activity through phosphorylation in macrophages, and the effect of PPARγ phosphorylation on macroph-ages-derived foam cell formation. Methods: After exposing the cultured THP-1 cells to ox-LDL in the presence or absence of different mitogen-activated proteinkinase (MAPK) inhibitors, PPARγ and phosphorylated PPARγ protein levels were detected by Western blot. MAPK activity was analyzed using MAP Kinase As-say Kit. Intracellular cholesterol accumulation was assessed by Oil red O staining and cholesterol oxidase enzymatic method. The mRNA level of PPARγ target genewas determined by reverse transcription-polymerase chain reaction (RT-PCR) .Results: ox-LDL evaluated PPARγ phosphorylation status and subsequently de-creased 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 depressed PPARγ phosphorylation induced by ox-LDL, which in turn inhibitedfoam cell formation. Conlusion: In addition to its ligand-dependent activation, ox-LDL modulates PPARγ activity through phosphorylation, which is mediatedby MAPK activation. PPARγ phosphorylation mediated by MAPK facilitatesfoam cell formation from macrophages exposed to ox-LDL.