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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride on hypoxia-induced β-amyloid production in SH-SY5Y cells

  • Han, A Reum (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • 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) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
  • Received : 2018.10.01
  • Accepted : 2018.10.24
  • Published : 2019.07.31
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Abstract

Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer's disease (AD), the molecular mechanism that determines the relationship between hypoxia-induced ${\beta}$-amyloid ($A{\beta}$) generation and development of AD is not yet known. We have now investigated the protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride (KHG26702), a novel thiazole derivative, on oxygen-glucose deprivation (OGD)-reoxygenation (OGD-R)-induced $A{\beta}$ production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with KHG26702 significantly attenuated OGD-R-induced production of reactive oxygen species and elevation of levels of malondialdehyde, prostaglandin $E_2$, interleukin 6 and glutathione, as well as superoxide dismutase activity. KHG26702 also reduced OGD-R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, KHG26702 reduced OGD-R-induced $A{\beta}$ production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that KHG26702 may prevent neuronal cell damage from OGD-R-induced toxicity.

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References

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