Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death.

Biochemical and Biophysical Research Communications
Shiguang GuoXiao-dong Wang

Abstract

Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13' cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E...Continue Reading

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Citations

Nov 26, 2016·Biochemical and Biophysical Research Communications·Sai ZhaoYue Xie
Nov 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Quancai SunYe Peng
Jun 19, 2019·Journal of Receptor and Signal Transduction Research·Ji-Ming PanMin Liang
Jun 3, 2017·Oncotarget·Hao-Dong FeiFeng Ji
Sep 25, 2017·Oncotarget·Zhenzhen JinAijun Yang
Jan 23, 2019·Acta Biochimica Et Biophysica Sinica·Rui HaoGuohai Su
Nov 27, 2019·Cell Death & Disease·Jinqian LiangMing-Sheng Tan
Mar 20, 2019·Neurochemical Research·Wilasinee SuwanjangKomgrid Charngkaew
Mar 30, 2018·Molecular Cancer Therapeutics·Min-Bin ChenCong Cao
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Oct 30, 2016·Biochemical and Biophysical Research Communications·Yong-Hong WuBei Liu
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Aug 3, 2021·Frontiers in Oncology·Yun-Rong ZhuYun-Qing Zhang

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