7-Chloroarctinone-b as a new selective PPAR gamma antagonist potently blocks adipocyte differentiation
文献类型：期刊论文
| 作者 | Li, Yong-tao2; Li, Li2; Chen, Jing1 ; Hu, Tian-cen1; Huang, Jin2; Guo, Yue-wei1; Jiang, Hua-liang1,2; Shen, Xu1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2009-09 |
| 卷号 | 30期号:9页码:1351-1358 |
| 关键词 | peroxisome proliferator-activated receptor antagonist surface plasmon resonance recruitment of the coactivator adipocyte differentiation |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2009.113 |
| 文献子类 | Article |
| 英文摘要 | Aim: Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a therapeutic target for obesity, cancer and diabetes mellitus. In order to develop potent lead compounds for obesity treatment, we screened a natural product library for novel PPAR gamma antagonists with inhibitory effects on adipocyte differentiation. Methods: Surface plasmon resonance (SPR) technology and cell-based transactivation assay were used to screen for PPAR gamma antagonists. To investigate the antagonistic mechanism of the active compound, we measured its effect on PPAR gamma/RXR alpha heterodimerization and PPAR gamma co-activator recruitment using yeast two-hybrid assay, Gal4/UAS cell-based assay and SPR based assay. The 3T3-L1 cell differentiation assay was used to evaluate the effect of the active compound on adipocyte differentiation. Results: A new thiophene-acetylene type of natural product, 7-chloroarctinone-b (CAB), isolated from the roots of Rhaponticum uniflorum, was discovered as a novel PPAR gamma antagonist capable of inhibiting rosiglitazone-induced PPAR gamma transcriptional activity. SPR analysis suggested that CAB bound tightly to PPAR gamma and considerably antagonized the potent PPAR gamma agonist rosiglitazone-stimulated PPAR gamma-LBD/RXR alpha-LBD binding. Gal4/UAS and yeast two-hybrid assays were used to evaluate the antagonistic activity of CAB on rosiglitazone-induced recruitment of the coactivator for PPAR gamma. CAB could efficiently antagonize both hormone and rosiglitazone-induced adipocyte differentiation in cell culture. Conclusion: CAB shows antagonistic activity to PPAR gamma and can block the adipocyte differentiation, indicating it may be of potential use as a lead therapeutic compound for obesity. |
| WOS关键词 | ACTIVATED RECEPTOR-GAMMA ; FATTY-ACIDS ; GENE-EXPRESSION ; 3T3-L1 CELLS ; ALPHA ; EICOSANOIDS ; AGONIST ; LIGAND ; REGULATOR ; SYSTEM |
| 资助项目 | National High Technology Research and Development Program of China[2006AA09Z447] ; National Natural Science Foundation of China[30890044] ; National Natural Science Foundation of China[90713046] ; National Natural Science Foundation of China[20721003] ; Shanghai Pujiang Program[PJ200700247] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3672211 |
| WOS记录号 | WOS:000269894400018 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279140]  |
| 专题 | 药物安全性评价中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 天然药物化学研究室 |
| 通讯作者 | Chen, Jing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Yong-tao,Li, Li,Chen, Jing,et al. 7-Chloroarctinone-b as a new selective PPAR gamma antagonist potently blocks adipocyte differentiation[J]. ACTA PHARMACOLOGICA SINICA,2009,30(9):1351-1358. |
| APA | Li, Yong-tao.,Li, Li.,Chen, Jing.,Hu, Tian-cen.,Huang, Jin.,...&Shen, Xu.(2009).7-Chloroarctinone-b as a new selective PPAR gamma antagonist potently blocks adipocyte differentiation.ACTA PHARMACOLOGICA SINICA,30(9),1351-1358. |
| MLA | Li, Yong-tao,et al."7-Chloroarctinone-b as a new selective PPAR gamma antagonist potently blocks adipocyte differentiation".ACTA PHARMACOLOGICA SINICA 30.9(2009):1351-1358. |
入库方式： OAI收割
来源：上海药物研究所
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