Arctigenin alleviates ER stress via activating AMPK
文献类型：期刊论文
| 作者 | Gu, Yuan3; Sun, Xiao-xiao3; Ye, Ji-ming1,5; He, Li3; Yan, Shou-sheng3; Zhang, Hao-hao3; Hu, Li-hong4; Yuan, Jun-ying2; Yu, Qiang3
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2012-07 |
| 卷号 | 33期号:7页码:941-952 |
| 关键词 | arctigenin ER stress human hepatocellular liver carcinoma cell beta-cell death mTOR-p70S6K eukaryotic translation elongation factor 2 (eEF2) mitochondrial respiration AMPK |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2012.60 |
| 文献子类 | Article |
| 英文摘要 | Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKK beta, LKB1, and AMPK alpha 1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5, and 10 mu mol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5, and 10 mu mol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPK alpha 1 with RNAi. ATG (1-50 mu mol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 mu mol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 mu mol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 beta cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. |
| WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; UNFOLDED PROTEIN RESPONSE ; ELONGATION-FACTOR-2 KINASE ; TRANSLATIONAL CONTROL ; INSULIN ACTION ; CANCER-CELLS ; PHOSPHORYLATION ; GROWTH ; DEPHOSPHORYLATION ; INHIBITION |
| 资助项目 | National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09301-001] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09103-064] ; China Ministry of Science and Technology Research Grant[2008ZX10002-020] ; Shanghai Science and Technology Research Grants[08DZ1971403] ; Shanghai Science and Technology Research Grants[09JC1416700] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000306103100011 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278024]  |
| 专题 | 药理学第一研究室 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 |
| 通讯作者 | Yu, Qiang |
| 作者单位 | 1.RMIT Univ, Hlth Innovat Res Inst, Melbourne, Vic, Australia; 2.Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Tumor Pharmacol, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 5.RMIT Univ, Sch Hlth Sci, Melbourne, Vic, Australia; |
| 推荐引用方式 GB/T 7714 | Gu, Yuan,Sun, Xiao-xiao,Ye, Ji-ming,et al. Arctigenin alleviates ER stress via activating AMPK[J]. ACTA PHARMACOLOGICA SINICA,2012,33(7):941-952. |
| APA | Gu, Yuan.,Sun, Xiao-xiao.,Ye, Ji-ming.,He, Li.,Yan, Shou-sheng.,...&Yu, Qiang.(2012).Arctigenin alleviates ER stress via activating AMPK.ACTA PHARMACOLOGICA SINICA,33(7),941-952. |
| MLA | Gu, Yuan,et al."Arctigenin alleviates ER stress via activating AMPK".ACTA PHARMACOLOGICA SINICA 33.7(2012):941-952. |
入库方式： OAI收割
来源：上海药物研究所
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。