Imiquimod-induced AMPK activation causes translation attenuation and apoptosis but not autophagy

Journal of Dermatological Science
Sin-Ting WangJeng-Jer Shieh

Abstract

AMP-activated protein kinase (AMPK), a principal intracellular energy sensor, plays a crucial role in cell growth, proliferation, apoptosis and autophagy. Imiquimod (IMQ) directly exhibits anti-tumor activity through the induction of apoptosis and autophagic cell death. To evaluate the role of AMPK in IMQ-induced apoptosis and autophagy. The phosphorylation of AMPK and its substrates was detected by immunoblotting. ATP contents were analyzed by an ATP bioluminescence assay. The upstream signaling for AMPK activation was dissected by examination of TLR7/8 expression, over-expression of TLR7/8, the addition of AMPK kinase inhibitors, and the genetic silencing of Myd88 and LKB1. The role of AMPK activation in IMQ-induced autophagy and apoptosis was assessed by inhibiting AMPK, genetically silencing AMPK and over-expressing AMPK dominant-negative mutants. Autophagy and apoptosis were evaluated by a DNA content assay, immunoblotting, EGFP-LC3 puncta detection and acridine orange staining. IMQ could activate AMPK and autophagy in cancer cells not expressing TLR7/8. IMQ caused ATP depletion and induced LKB1-mediated AMPK activation. The down-regulation of AMPK activity via pharmacological inhibition and genetic silencing resulted in r...Continue Reading

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Citations

Jan 19, 2016·Journal of Dermatological Science·Shi-Wei HuangJeng-Jer Shieh
Feb 17, 2019·Journal of Cellular Physiology·Reza MohammadinejadMilad Ashrafizadeh
Sep 19, 2019·Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry·Humaira B NoorMd A T Sagor
Jun 2, 2017·Experimental and Therapeutic Medicine·Tiancheng XieYunfei Xu
Jan 8, 2020·AAPS PharmSciTech·Luiza Abrahão FrankSilvia S Guterres
Mar 22, 2021·The Journal of Investigative Dermatology·Shu-Hao ChangJeng-Jer Shieh

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