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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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Received: 17 March 2014; in revised form: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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). International Journal of Molecular Sciences. 2014; 15(6):11190-11203.

Chicago/Turabian Style

Zhu, Yalong; Zhou, Jianhua; Ao, Rongguang; Yu, Baoqing. 2014. "A-769662 Protects Osteoblasts from Hydrogen Dioxide-Induced Apoptosis through Activating of AMP-Activated Protein Kinase (AMPK)." Int. J. Mol. Sci. 15, no. 6: 11190-11203.



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