Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows extensive cellular effects on PI3K/AKT activation, glucose transport, and TGF beta/Smad2 signaling
文献类型：期刊论文
| 作者 | Sun, Tao; Wang, Qi; Yu, Zhiguo; Zhang, Yu; Guo, Yuewei ; Chen, Kaixian; Shen, Xu; Jiang, Hualiang
|
| 刊名 | CHEMBIOCHEM
 |
| 出版日期 | 2007-01-22 |
| 卷号 | 8期号:2页码:187-193 |
| 关键词 | hyrtiosal inhibitors natural products PI3K/AKT protein tyrosine phosphatases |
| ISSN号 | 1439-4227 |
| DOI | 10.1002/cbic.200600349 |
| 文献子类 | Article |
| 英文摘要 | Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling,and PTP1B inhibitors have been seen as promising therapeutic agents against obesity and type 2 diabetes. Here we report that the marine natural product hyrtiosal, from the marine sponge Hyrtios erectus, has been discovered to act as a PTP1B inhibitor and to show extensive cellular effects on PI3K/AKT activation, glucose transport, and TGF beta/Smad2 signaling. This inhibitor wad able to inhibit PTP1B activity in dose-dependent fashion, with an IC50 value of 42 mu m in a noncompetitive inhibition mode. Further study with an IN Cell Analyzer 1000 cellular fluorescence imaging instrument showed that hyrtiosal displayed potent activity in abolishing the retardation of AKT membrane translocation caused by PTP1B overexpression in CHO cells. Moreover, it was found that this newly identified PTP1B inhibitor could dramatically enhance the membrane translocation of the key glucose transporter Glut4 in PTP1B-overexpressed CHO cells. Additionally, in view of our recent finding that PTP1B was able to modulate insulin-mediated inhibition of Smad2 activation, hyrtiosal was also tested for its capabilities in the regulation of Smad2 activity through the PI3K/AKT pathway. The results showed that hyrtiosal could effectively facilitate insulin inhibition of Smad2 activation. Our current study is expected to supply new clues for the discovery of PTP1B inhibitors from marine natural products, while the newly identified PTP1B inhibitor hyrtiosal might serve as potential lead compound for further research. |
| WOS关键词 | TYROSINE-PHOSPHATASE 1B ; STIMULATED GLUT4 TRANSLOCATION ; BETA-INDUCED APOPTOSIS ; STRUCTURE-BASED DESIGN ; PHOSPHOINOSITIDE 3-KINASE ; INSULIN SENSITIVITY ; DEPENDENT PATHWAY ; HEPATOMA-CELLS ; RESISTANCE ; OBESITY |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000243810000007 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273349]  |
| 专题 | 天然药物化学研究室 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 药物发现与设计中心 药理学第三研究室 |
| 通讯作者 | Guo, Yuewei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, 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 | Sun, Tao,Wang, Qi,Yu, Zhiguo,et al. Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows extensive cellular effects on PI3K/AKT activation, glucose transport, and TGF beta/Smad2 signaling[J]. CHEMBIOCHEM,2007,8(2):187-193. |
| APA | Sun, Tao.,Wang, Qi.,Yu, Zhiguo.,Zhang, Yu.,Guo, Yuewei.,...&Jiang, Hualiang.(2007).Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows extensive cellular effects on PI3K/AKT activation, glucose transport, and TGF beta/Smad2 signaling.CHEMBIOCHEM,8(2),187-193. |
| MLA | Sun, Tao,et al."Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows extensive cellular effects on PI3K/AKT activation, glucose transport, and TGF beta/Smad2 signaling".CHEMBIOCHEM 8.2(2007):187-193. |
入库方式： OAI收割
来源：上海药物研究所
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