Arctigenin alleviates ER stress via activating AMPK

Gu, Y, Sun, X, Ye, J, He, L, Yan, S, Zhang, H, Hu, L, Yuan, J and Yu, Q 2012, 'Arctigenin alleviates ER stress via activating AMPK', Acta Pharmacologica Sinica, vol. 33, no. 7, pp. 941-952.

Document type: Journal Article
Collection: Journal Articles

Title Arctigenin alleviates ER stress via activating AMPK
Author(s) Gu, Y
Sun, X
Ye, J
He, L
Yan, S
Zhang, H
Hu, L
Yuan, J
Yu, Q
Year 2012
Journal name Acta Pharmacologica Sinica
Volume number 33
Issue number 7
Start page 941
End page 952
Total pages 12
Publisher Nature Publishing Group
Abstract 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 CaMKKß, LKB1, and AMPKa1 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 µmol/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 µmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKa1 with RNAi. ATG (1-50 µmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 µmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 µmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 ß 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.
Subject Pharmacology and Pharmaceutical Sciences not elsewhere classified
Keyword(s) ß-cell death
ER stress
eukaryotic translation elongation factor 2 (eEF2)
human hepatocellular liver carcinoma cell
mitochondrial respiration
DOI - identifier 10.1038/aps.2012.60
Copyright notice © 2012 CPS and SIMM
ISSN 1671-4083
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
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