Enhanced VDUP-1 gene expression by PPARgamma agonist induces apoptosis in human macrophage.

Billiet L; Furman C; Larigauderie GCopin CPage SFruchart JCBrand KRouis M

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Enhanced VDUP-1 gene expression by PPARgamma agonist induces apoptosis in human macrophage.

机译：增强VDUP-1 PPARgamma基因表达受体激动剂人类巨噬细胞发生凋亡。

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The fate and phenotype of lesion macrophages is regulated by cellular oxidative stress. Thioredoxin-1 (Trx-1) plays a major role in the regulation of cellular redox balance, with resultant effects on gene expression and cellular responses including cell growth and death. Trx-1 activity is inhibited by interaction with vitamin D-upregulated protein-1 (VDUP-1). Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed by human monocyte-derived macrophages (HMDM) and PPARgamma agonism has been reported to decrease expression of inflammatory genes and to promote apoptosis of these cells. To determine whether VDUP-1 may be involved in regulating the effects of PPARgamma agonists in macrophages, we investigated the effect of a synthetic PPARgamma agonist (GW929) on the expression of VDUP-1 in HMDM. GW929 concentration-dependently increased HMDM expression of VDUP-1 (mRNA and protein). Transfection of different fragments of the VDUP-1 promoter as well as gel shift analysis revealed the presence of functional PPARgamma response elements (PPRE) in the promoter. Under conditions in which PPAR agonism altered levels of VDUP-1, caspase-3 activity, and macrophage apoptosis were also elevated. The results suggest that PPARgamma activation stimulates apoptosis in human macrophages by altering the cellular redox balance via regulation of VDUP-1.

机译：命运和病变巨噬细胞的表型受细胞氧化应激。Thioredoxin-1 (Trx-1)过程中起着重要作用调节细胞氧化还原平衡,对基因表达和细胞合成的影响包括细胞生长和死亡的反应。活动是由交互抑制维生素D-upregulated蛋白1 (VDUP-1)。proliferator-activated受体γ(PPARgamma)所表达的是人类monocyte-derived巨噬细胞(HMDM)和PPARgamma激动据报道,减少炎症的表情这些细胞的基因和促进细胞凋亡。确定是否VDUP-1可能参与调节PPARgamma受体激动剂的影响巨噬细胞,我们调查的影响合成PPARgamma受体激动剂(GW929)的表达在HMDM VDUP-1。concentration-dependently HMDM增加表达VDUP-1(信使rna和蛋白质)。转染VDUP-1不同的片段启动子分析显示以及凝胶转变功能性PPARgamma反应的存在在启动子元素(PPRE)。中PPAR激动VDUP-1水平改变,caspase-3活动,巨噬细胞凋亡也升高。激活刺激细胞凋亡在人类巨噬细胞通过改变细胞氧化还原通过调节VDUP-1平衡。

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来源
《Journal of Cellular Physiology》 |2008年第1期|183-191|共9页
作者
Billiet L; Furman C; Larigauderie GCopin CPage SFruchart JCBrand KRouis M;
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Inserm, U-545, Lille, France.;

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正文语种英语
中图分类细胞生物学;
关键词
Cell culture; Aorta; AgonistCulture TechniquesCell DifferentiationGel Shift AnalysisApoptosisCaspase 3CASP3 genereversed field pinchCarrier ProteinsMacrophagesBinding ProteinPPAR gamma;

机译：细胞培养;主动脉;AgonistCulture TechniquesCellDifferentiationGel AnalysisApoptosisCaspase转变3 casp3 pinchCarrier genereversed字段ProteinsMacrophagesBinding ProteinPPARγ;

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Enhanced VDUP-1 gene expression by PPARgamma agonist induces apoptosis in human macrophage.

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