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Int. J. Mol. Sci. 2014, 15(6), 11190-11203; doi:10.3390/ijms150611190
Article

A-769662 Protects Osteoblasts from Hydrogen Dioxide-Induced Apoptosis through Activating of AMP-Activated Protein Kinase (AMPK)

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,
 and
*
Orthopedics Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 17 March 2014 / Revised: 14 April 2014 / Accepted: 4 May 2014 / Published: 23 June 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract

Here we report that 5'-monophosphate (AMP)-activated protein kinase (AMPK) agonist A-769662 inhibited hydrogen peroxide (H2O2)-induced viability loss and apoptosis of human and mouse osteoblast cells. H2O2-induced moderate AMPK activation in osteoblast cells, which was enhanced by A-769662. Inactivation of AMPK by its inhibitor compound C, or by target shRNA-mediated silencing and kinase dead (KD) mutation exacerbated H2O2-induced cytotoxicity in osteoblast cells. A-769662-mediated protective effect against H2O2 was also blocked by AMPK inhibition or depletion. A-769662 inhibited reactive oxygen species (ROS) accumulation by H2O2 in osteoblast cells. Meanwhile, H2O2-induced ATP depletion was inhibited by A-769662, but was aggravated by compound C. Further, H2O2 induced AMPK-dependent and pro-survival autophagy in cultured osteoblast cells, which was enhanced by A-769662. Our results suggested that activation of AMPK by H2O2 is anti-apoptosis and pro-survival in osteoblast cells, probably due to its anti-oxidant, pro-autophagy and ATP preservation abilities, and A-769662-mediated cell-protective effect in osteoblast cells requires AMPK activation. Our study suggests that A-769662 might be further investigated as a novel anti-osteonecrosis agent.
Keywords: osteonecrosis; AMPK; A-769662; oxidative stress and apoptosis osteonecrosis; AMPK; A-769662; oxidative stress and apoptosis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Zhu, Y.; Zhou, J.; Ao, R.; Yu, B. A-769662 Protects Osteoblasts from Hydrogen Dioxide-Induced Apoptosis through Activating of AMP-Activated Protein Kinase (AMPK). Int. J. Mol. Sci. 2014, 15, 11190-11203.

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