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Targeted Activation of AMPK by GSK621 Ameliorates H2O2-induced Damages in Osteoblasts

Targeted Activation of AMPK by GSK621 Ameliorates H2O2-induced Damages in Osteoblasts

Weidong Liu, Li Mao, Feng Ji, Fengli Chen, Yuedong Hao, Gang Liu

Oncotarget. 2017 Feb 7;8(6):10543-10552.

PMID: 28060740

Abstract:

GSK621 is a novel AMP-activated protein kinase (AMPK) activator. This study tested its potential cytoprotective effect in hydrogen peroxide (H2O2)-treated osteoblasts. In cultured MC3T3-E1 osteoblastic cells and primary murine osteoblasts, GSK621 significantly attenuated H2O2-induced cell death and apoptosis. AMPK activation was required for GSK621-induced osteoblast cytoprotection. Inhibition of AMPK, by AMPKα1 T172A mutation or shRNA silence, almost completely blocked GSK621-induced osteoblast cytoprotection. Reversely, introduction of a constitutively-active AMPKα1 (T172D) alleviated H2O2 injuries in MC3T3-E1 cells. Further, GSK621 increased nicotinamide adenine dinucleotide phosphate (NADPH) content in osteoblasts to inhibit H2O2-induced reactive oxygen species (ROS) production. Meanwhile, GSK621 activated cytoprotective autophagy in the osteoblasts. On the other hand, pharmacological inhibition of autophagy alleviated GSK621-mediated osteoblast cytoprotection against H2O2. These results suggest that targeted activation of AMPK by GSK621 ameliorates H2O2-induced osteoblast cell injuries.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1346607053	GSK621		1346607-05-3	Price

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