Oleanolic acid derivative NPLC441 potently stimulates glucose transport in 3T3-L1 adipocytes via a multi-target mechanism
文献类型：期刊论文
| 作者 | Lin, Zhonghui; Zhang, Yu; Zhang, Yinan; Shen, Hong; Hu, Lihong; Jiang, Hualiang ; Shen, Xu
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| 刊名 | BIOCHEMICAL PHARMACOLOGY
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| 出版日期 | 2008-11-15 |
| 卷号 | 76期号:10页码:1251-1262 |
| 关键词 | Oleanolic acid PTP1B LXR alpha:RXR alpha RXR Antagonist 11 beta-HSD1 |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2008.08.016 |
| 文献子类 | Article |
| 英文摘要 | The natural product oleanolic acid (OA) has been discovered to exhibit varied pharmacological functions including anti-inflammation, anti-tumor and anti-diabetes, while appropriate synthetic oleanolic acid derivatives seem to possess more potent activities. Here we identified a new oleanolic acid derivative, 3-beta-(2-carboxybenzoyloxy)-oleanolic acid (NPLC441), which functioned as a competitive PTP1B inhibitor and enhanced insulin stimulated phosphorylation of IR and AKT in HepG2 cells. As an RXR alpha antagonist, it could selectively activate LXR alpha:RXR alpha heterodimer and increase the promoter activities of ABCA1 and ABCG1 genes in transient transfection assays. Quantitative RT-PCR and Western blot analyses suggested that NPLC441 could up-regulate GLUT4 expression in 3T3-L1 adipocytes, and such effect was further proved to be dependent on LXR alpha:RXR alpha activation. Moreover, 2-deoxyglucose uptake technology-based characterization demonstrated that this compound could stimulate glucose uptake in 3T3-L1 adipocytes. Finally, NPLC441 was observed to be able to suppress 11 beta-HSD1 expression in HepG2 cells, following the discovery that activation of LXRa:RXRa could repress the expression of 11 beta-HSD1. Compared with NPLC441, OA showed no effects on the transactivation of either LXR alpha:RXR alpha heterodimer or RXR alpha-LBD. our work is thus expected to provide a new insight into the anti-diabetic application for oleanolic acid derivatives via multi-target mechanism, and NPLC441 could be used as a potential lead compound for further research. (C) 2008 Elsevier Inc. All rights reserved. |
| WOS关键词 | LIVER-X-RECEPTOR ; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 ; TYROSINE-PHOSPHATASE 1B ; PROLIFERATOR-ACTIVATED RECEPTOR ; RAT ADIPOSE-CELLS ; HUMAN ABCG1 GENE ; INSULIN-RECEPTOR ; URSOLIC ACID ; PTP1B INHIBITOR ; PPAR-GAMMA |
| 资助项目 | State Key Program of Basic Research of China[2004CB518905] ; State Key Program of Basic Research of China[2006AA09Z447] ; State Key Program of Basic Research of China[2007CB914304] ; National Natural Science Foundation of China[30525024] ; National Natural Science Foundation of China[90713046] ; National Natural Science Foundation of China[20721003] ; Shanghai Science and Technology Commission[06JC14080] ; Shanghai Science and Technology Commission[03DZ19228] ; CAS Foundation[KSCX2-YW-R-18] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000260950300008 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279432]  |
| 专题 | 上海中药现代化研究中心 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 药理学第三研究室 |
| 通讯作者 | Hu, Lihong |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, Zhonghui,Zhang, Yu,Zhang, Yinan,et al. Oleanolic acid derivative NPLC441 potently stimulates glucose transport in 3T3-L1 adipocytes via a multi-target mechanism[J]. BIOCHEMICAL PHARMACOLOGY,2008,76(10):1251-1262. |
| APA | Lin, Zhonghui.,Zhang, Yu.,Zhang, Yinan.,Shen, Hong.,Hu, Lihong.,...&Shen, Xu.(2008).Oleanolic acid derivative NPLC441 potently stimulates glucose transport in 3T3-L1 adipocytes via a multi-target mechanism.BIOCHEMICAL PHARMACOLOGY,76(10),1251-1262. |
| MLA | Lin, Zhonghui,et al."Oleanolic acid derivative NPLC441 potently stimulates glucose transport in 3T3-L1 adipocytes via a multi-target mechanism".BIOCHEMICAL PHARMACOLOGY 76.10(2008):1251-1262. |
入库方式： OAI收割
来源：上海药物研究所
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