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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Protective effect of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride on hypoxia-induced toxicity by suppressing microglial activation in BV-2 cells

  • Kim, Jiae (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Kim, Su-Min (Department of Biomedical Laboratory Science, Konyang University) ;
  • Na, Jung-Min (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Hahn, Hoh-Gyu (Chemical Kinomics Research Center, Korea Institute of Science and Technology) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Yang, Seung-Ju (Department of Biomedical Laboratory Science, Konyang University)
  • Received : 2016.10.06
  • Accepted : 2016.10.19
  • Published : 2016.12.31
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Abstract

We recently reported the anti-inflammatory effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) on the ATP-induced activation of the NFAT and MAPK pathways through the P2X7 receptor in microglia. To further investigate the underlying mechanism of KHG26792, we studied its protective effects on hypoxia-induced toxicity in microglia. The administration of KHG26792 significantly reduced the hypoxia-induced expression and activity of caspase-3 in BV-2 microglial cells. KHG26792 also reduced hypoxia-induced inducible nitric oxide synthase protein expression, which correlated with reduced nitric oxide accumulation. In addition, KHG26792 attenuated hypoxia-induced protein nitration, reactive oxygen species production, and NADPH oxidase activity. These effects were accompanied by the suppression of hypoxia-induced protein expression of hypoxia-inducible factor 1-alpha and NADPH oxidase-2. Although the clinical relevance of our findings remains to be determined, these data results suggest that KHG26792 prevents hypoxia-induced toxicity by suppressing microglial activation.

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References

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