7chloroarctinonebasanewselectivepparantagonistpotentlyblocksadipocytedifferentiation
文献类型：期刊论文
| 作者 | Yongtao LI1; Li LI1; Jing CHEN2 ; Tiancen HU2; Jin HUANG1; Yuewei GUO2; Hualiang JIANG1; Xu SHEN1
|
| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2009 |
| 卷号 | 30期号:9页码:1351 |
| 关键词 | peroxisome proliferator-activated receptor antagonist surface plasmon resonance recruitment of the coactivator adipocyte differentiation |
| ISSN号 | 1671-4083 |
| 英文摘要 | Aim: Peroxisome proliferator-activated receptor gamma (PPARy) 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 PPARy antagonists with inhibitory effects on adipocyte differentiation. Methods: Surface plasmon resonance (SPR) technology and cell-based transactivation assay were used to screen for PPARy antago-nists. To investigate the antagonistic mechanism of the active compound, we measured its effect on PPARy/RXRα heterodimerization and PPARy 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 uniflo-rum, was discovered as a novel PPARγ antagonist capable of inhibiting rosiglitazone-induced PPARγ transcriptional activity. SPR analy-sis suggested that CAB bound tightly to PPARγ and considerably antagonized the potent PPARy agonist rosigtitazone-stimulated PPARγ-LBD/RXRα-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 PPARy. CAB could efficiently antagonize both hormone and rosiglitazone-induced adipocyte differentiation in cell culture. Conclusion: CAB shows antagonistic activity to PPARγ and can block the adipocyte differentiation, indicating it may be of potential use as a lead therapeutic compound for obesity. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/284685]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.华东理工大学 2.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Yongtao LI,Li LI,Jing CHEN,et al. 7chloroarctinonebasanewselectivepparantagonistpotentlyblocksadipocytedifferentiation[J]. actapharmacologicasinica,2009,30(9):1351. |
| APA | Yongtao LI.,Li LI.,Jing CHEN.,Tiancen HU.,Jin HUANG.,...&Xu SHEN.(2009).7chloroarctinonebasanewselectivepparantagonistpotentlyblocksadipocytedifferentiation.actapharmacologicasinica,30(9),1351. |
| MLA | Yongtao LI,et al."7chloroarctinonebasanewselectivepparantagonistpotentlyblocksadipocytedifferentiation".actapharmacologicasinica 30.9(2009):1351. |
入库方式： OAI收割
来源：上海药物研究所
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