Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway

Jianxiong Li; Bin Li; Yujie Bu; Hailin Zhang; Jia Guo; Jianping Hu; Yanfang Zhang

doi:10.14348/molcells.2021.0071

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자료유형: 학술저널

저자정보: Jianxiong Li (Lanzhou University Second Hospital) Bin Li (Lanzhou University Second Hospital) Yujie Bu (Lanzhou University Second Hospital) Hailin Zhang (Lanzhou University Second Hospital) Jia Guo (Lanzhou University Second Hospital) Jianping Hu (Lanzhou University Second Hospital) Yanfang Zhang (Lanzhou University Second Hospital)

저널정보: 한국분자세포생물학회 Molecules and Cells Molecules and Cells 제45권 제4호

발행연도: 2022.4

수록면: 216 - 230 (15page)

DOI: 10.14348/molcells.2021.0071

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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.

#CDK4 #neurological injury #oxygen-glucose deprivation/reoxygenation #p-Rb #Sertad1

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