|
KMID : 0578320220450040216
|
|
Molecules and Cells
2022 Volume.45 No. 4 p.216 ~ p.230
|
|
|
Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway
|
|
Li Jianxiong
Li Bin
Bu Yujie
Zhang Hailin
Guo Jia
Hu Jianping
Zhang Yanfang
|
|
|
Abstract
|
|
|
|
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.
|
|
|
KEYWORD
|
|
|
CDK4, neurological injury, oxygen-glucose deprivation/reoxygenation, p-Rb, Sertad1
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|