Novel mechanism of inhibition of nuclear factor-kappa B DNA-binding activity by diterpenoids isolated from Isodon rubescens
文献类型：期刊论文
| 作者 | Leung, CH; Grill, SP; Lam, W; Han, QB; Sun, HD ; Cheng, YC
|
| 刊名 | MOLECULAR PHARMACOLOGY
 |
| 出版日期 | 2005-08-01 |
| 卷号 | 68期号:2页码:286-297 |
| 英文摘要 | The development of specific inhibitors that can block nuclear factor-kappa B (NF-kappa B) activation is an approach for the treatment of cancer, autoimmune, and inflammatory diseases. Several diterpenoids, oridonin, ponicidin, xindongnin A, and xindongnin B were isolated from the herb Isodon rubescens. These compounds were found to be potent inhibitors of NF-kappa B transcription activity and the expression of its downstream targets, cyclooxygenase-2 and inducible nitric-oxide synthase. The mechanisms of action of the diterpenoids against NF-kappa B are similar, but significant differences were also identified. All of the diterpenoids directly interfere with the DNA-binding activity of NF-kappa B to its response DNA sequence. Oridonin and ponicidin have an additional impact on the translocation of NF-kappa B from the cytoplasm to nuclei without affecting I kappa B-alpha phosphorylation and degradation. The effect of these compounds on the interaction of NF-kappa B with consensus DNA sequences is unique. Different inhibitory effects were observed when NF-kappa B bound to various DNA sequences. Both p65/p65 and p50/p50 homodimers, as well as p65/p50 heterodimer association with their responsive DNA, were inhibited. Kinetic studies on NF-kappa B-DNA interaction indicate that the diterpenoids decrease the B-max (app) but have no effect on K-d app. This suggests that this class of compounds interacts with both p65 and p50 subunits at a site other than the DNA binding site and subsequently modulates the binding affinity of the transcription factor toward DNA with different NF-kappa B binding sequences. The diterpenoid structure could therefore serve as a scaffold for the development of more potent and selective NF-kappa B inhibitors that target regulated gene transcription. |
| 类目[WOS] | Pharmacology & Pharmacy |
| 研究领域[WOS] | Pharmacology & Pharmacy |
| 关键词[WOS] | ENT-KAURANE DITERPENOIDS ; PROTEIN-KINASE-C ; VAR.-RUBESCENS ; CANCER ; TRANSCRIPTION ; EXPRESSION ; ORIDONIN ; PATHWAY ; TARGET ; GLUCOCORTICOIDS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000230549900005 |
| 公开日期 | 2015-12-24 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/24792]  |
| 专题 | 昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室 |
| 作者单位 | 1.Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Beijing 100864, Peoples R China |
| 推荐引用方式 GB/T 7714 | Leung, CH,Grill, SP,Lam, W,et al. Novel mechanism of inhibition of nuclear factor-kappa B DNA-binding activity by diterpenoids isolated from Isodon rubescens[J]. MOLECULAR PHARMACOLOGY,2005,68(2):286-297. |
| APA | Leung, CH,Grill, SP,Lam, W,Han, QB,Sun, HD,&Cheng, YC.(2005).Novel mechanism of inhibition of nuclear factor-kappa B DNA-binding activity by diterpenoids isolated from Isodon rubescens.MOLECULAR PHARMACOLOGY,68(2),286-297. |
| MLA | Leung, CH,et al."Novel mechanism of inhibition of nuclear factor-kappa B DNA-binding activity by diterpenoids isolated from Isodon rubescens".MOLECULAR PHARMACOLOGY 68.2(2005):286-297. |
入库方式： OAI收割
来源：昆明植物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。