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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates MPP+-induced cytotoxicity by regulating oxidative stress and mitochondrial dysfunction in SH-SY5Y cells

  • Yang, Seung-Ju (Department of Biomedical Laboratory Science, Konyang University) ;
  • Yang, Ji Woong (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Na, Jung-Min (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Ha, Ji Sun (Department of Biomedical Laboratory Science, Konyang University) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
  • Received : 2018.06.04
  • Accepted : 2018.06.28
  • Published : 2018.11.30
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Abstract

Parkinson's disease (PD) is a common chronic neurodegenerative disease mainly caused by the death of dopaminergic neurons. However, no complete pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl-4-phenylpyridinium $(MPP^+)$-induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms and critical aspects of PD. In the present study, we examined the role of a novel azetidine derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792), against $MPP^+$-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792 significantly attenuated $MPP^+$-induced changes in the protein levels of Bcl-2 and Bax together with efficient suppression of $MPP^+$-induced activation of caspase-3 activity. KHG26792 also attenuated mitochondrial potential and levels of ROS, $Ca^{2+}$, and ATP in $MPP^+$-treated SH-SY5Y cells. Additionally, KHG26792 inhibited the induced production of nitric oxide and malondialdehyde. Moreover, the protective effect of KHG26792 is mediated through regulation of glutathione peroxidase and GDNF levels. Our results suggest a possibility that KHG26792 treatment significantly protects against $MPP^+$-induced neurotoxicity in SH-SY5Y cells and KHG26792 may be a valuable therapeutic agent for the treatment of PD induced by an environmental toxin.

Keywords

References

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