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PPARγ phosphorylation mediated by JNK MAPK:a potential role in mac-rophage-derived foam cell formation

Acta Pharmacologica Sinica 2006年第9期27卷 1146-1152页

作者： Ran YIN~2 Yu-gang DONG~(2,4)Hong-liang LI~3 Z Department of Cardiology,First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China 3 Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Beijing 100005,China Department of Cardiology First Affiliated Hospital Sun Yat-sen University Guangzhou China Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Beijing China

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 ***: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 *** activity was analyzed using MAP Kinase As-say *** cholesterol accumulation was assessed by Oil red O stainingand cholesterol oxidase enzymatic *** 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 *** 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 ***:In addition to its ligand-dependent activation,ox-ldl modulates PPARγ activity through phosphorylation,which is mediatedby MAPK ***γ phosphorylation mediated by MAPK facilitatesfoam cell formation from macrophages exposed to ox-ldl.

关键词： peroxisome proliferator-activated receptorγ phosphorylation macrophages ldl lipoprotein

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Effects of CpG-ODN on gene expression in formation of foam cells

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Acta Pharmacologica Sinica 2005年第11期26卷 1359-1364页

作者： Kai LI, Bin WAN, Zhen-lin HU, Ying HE, Xiao-wen HE, Lei JIANG, Shu-han SUN~2 Department of Medical Genetics, College of Basic Medical Sciences, the Second Military Medical University, Shanghai 200433, China Department of Medical Genetics College of Basic Medical Sciences the Second Military Medical University Shanghai China

Aim: To investigate the effects of CpG-oligodeoxynucleotide (CpG-ODN) on the formation of macrophage foam cells and related gene expression. Methods: A gene expression profile was examined by microarray techniques, and mRNA expression was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The cholesterol and cholesteryl ester contents of cells were determined by high performance liquid chromatography. Results: CD36, LPL, and Fcγ2b, which were related to lipid metabolism and the formation of macrophage foam cells, were upregulated after CpG-ODN stimulation. The mRNA expression related to the formation of foam cells was confirmed by semiquantitative RT-PCR. Moreover, histochemical analysis confirmed that lipid deposits inside cells increased after CpG-ODN treatment. However, using flow cytometry, we found that CpG-ODN had no effect on the expression of membrane receptors. Conclusion: CpG-ODN up-regulated the expression of genes in macrophage foam cell formation.

关键词： CpG islands oligodeoxyribonucleotides foam cells macrophages ldl lipoprotein gene expression cholesterol CD 36 antigens lipoprotein lipase Fc gamma receptor Ⅱb

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