Pinacidil protects osteoblastic cells against antimycin A-induced oxidative damage

  • Authors:
    • Eun Mi Choi
    • Woon Won Jung
    • Kwang Sik Suh
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  • Published online on: October 21, 2014     https://doi.org/10.3892/mmr.2014.2721
  • Pages: 746-752
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Abstract

The present study aimed to investigate the protective effect of a non-selective mitochondrial adenosine triphosphate (ATP)-sensitive potassium channel (mito-KATP) opener, pinacidil, on antimycin A-induced oxidative damage in osteoblastic MC3T3-E1 cells. Antimycin A inhibits mitochondrial electron transport by binding to complex III. Osteoblastic MC3T3-E1 cells were treated with antimycin A in the presence or absence of pinacidil and markers of mitochondrial function and oxidative stress were subsequently examined. The effects of pinacidil on the activation of phosphoinositide 3-kinase (PI3K), Akt and cyclic adenosine monophosphate‑responsive element-binding protein (CREB) were also examined. In osteoblastic MC3T3-E1 cells exposed to antimycin A, pinacidil inhibited antimycin A-induced cell death. The protective effects of pinacidil on cell survival were prevented by the addition of LY294002 (a PI3K inhibitor), an Akt inhibitor or auranofin [a thioredoxin reductase (TrxR) inhibitor], but not by KATP channel inhibitor glibenclamide. Pinacidil inhibited antimycin A-induced inactivation of PI3K and Akt as well as phosphorylation of CREB and TrxR. Furthermore, pinacidil prevented antimycin A-induced mitochondrial superoxide release, mitochondrial membrane potential dissipation, reduced ATP synthesis and intracellular [Ca2+] elevation. In conclusion, these results suggested that pinacidil may rescue osteoblastic cells from antimycin A-induced cellular damage, potentially via antioxidant activity and restoration of mitochondrial function, which are mediated in part by the PI3K/Akt/CREB signaling pathway.
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January-2015
Volume 11 Issue 1

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Spandidos Publications style
Choi EM, Jung WW and Suh KS: Pinacidil protects osteoblastic cells against antimycin A-induced oxidative damage. Mol Med Rep 11: 746-752, 2015
APA
Choi, E.M., Jung, W.W., & Suh, K.S. (2015). Pinacidil protects osteoblastic cells against antimycin A-induced oxidative damage. Molecular Medicine Reports, 11, 746-752. https://doi.org/10.3892/mmr.2014.2721
MLA
Choi, E. M., Jung, W. W., Suh, K. S."Pinacidil protects osteoblastic cells against antimycin A-induced oxidative damage". Molecular Medicine Reports 11.1 (2015): 746-752.
Chicago
Choi, E. M., Jung, W. W., Suh, K. S."Pinacidil protects osteoblastic cells against antimycin A-induced oxidative damage". Molecular Medicine Reports 11, no. 1 (2015): 746-752. https://doi.org/10.3892/mmr.2014.2721