Arctigenin alleviates ER stress via activating AMPK

doi:10.1038/aps.2012.60

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Arctigenin alleviates ER stress via activating AMPK
	Gu, Yuan 3; Sun, Xiao-xiao 3; Ye, Ji-ming 1,5; He, Li 3; Yan, Shou-sheng 3; Zhang, Hao-hao 3; Hu, Li-hong 4; Yuan, Jun-ying 2; Yu, Qiang3
刊名	ACTA PHARMACOLOGICA SINICA
	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.
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关键词	ENDOPLASMIC-RETICULUM STRESS ; UNFOLDED PROTEIN RESPONSE ; ELONGATION-FACTOR-2 KINASE ; TRANSLATIONAL CONTROL ; INSULIN ACTION ; CANCER-CELLS ; PHOSPHORYLATION ; GROWTH ; DEPHOSPHORYLATION ; INHIBITION
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000306103100011
内容类型	期刊论文
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.