Molecules and Cells

  • 제45권4호
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  • Pages.216-230
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  • 2022
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway

  • Li, Jianxiong (Department of Neurology, Lanzhou University Second Hospital) ;
  • Li, Bin (Department of Neurology, Lanzhou University Second Hospital) ;
  • Bu, Yujie (Department of Neurology, Lanzhou University Second Hospital) ;
  • Zhang, Hailin (Neurosurgery, Lanzhou University Second Hospital) ;
  • Guo, Jia (Department of Neurology, Lanzhou University Second Hospital) ;
  • Hu, Jianping (Department of Neurology, Lanzhou University Second Hospital) ;
  • Zhang, Yanfang (Department of Neurology, Lanzhou University Second Hospital)
  • 투고 : 2021.03.25
  • 심사 : 2021.12.09
  • 발행 : 2022.04.30
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초록

SERTA domain-containing protein 1 (Sertad1) is upregulated in the models of DNA damage and Alzheimer's disease, contributing to neuronal death. However, the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury remain unclear. In the present study, our results showed that the expression of Sertad1 was upregulated in a mouse middle cerebral artery occlusion and reperfusion model and in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown significantly ameliorated ischemia-induced brain infarct volume, neurological deficits and neuronal apoptosis. In addition, it significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Sertad1 knockdown significantly inhibited the ischemic/hypoxic-induced expression of p-Rb, B-Myb, and Bim in vivo and in vitro. However, Sertad1 overexpression significantly exacerbated the OGD/R-induced inhibition of cell viability and apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we demonstrated that Sertad1 directly binds to CDK4 and the CDK4 inhibitor ON123300 restores the effects of Sertad1 overexpression on OGD/R-induced apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. These results suggested that Sertad1 contributed to ischemic/hypoxic neurological injury by activating the CDK4/p-Rb pathway.

키워드

과제정보

This study was supported by grants from the Science and Technology Program of Chengguan District, Lanzhou City (grant No. 2017SHFZ0035) and the training program of the Cuiying graduate tutor.

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