Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway
SERTA domain-that contains protein 1 (Sertad1) is upregulated within the types of DNA damage and Alzheimer’s, adding to neuronal dying. However, the function and mechanism of Sertad1 in ischemic/hypoxic nerve injuries remain unclear. In our study, our results demonstrated the expression of Sertad1 was upregulated inside a mouse middle cerebral artery occlusion and reperfusion model as well as in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown considerably ameliorated ischemia-caused brain infarct volume, nerve deficits and neuronal apoptosis. Additionally, it considerably ameliorated the OGD/R-caused inhibition of cell viability and apoptotic cell dying in HT22 cells. Sertad1 knockdown considerably inhibited the ischemic/hypoxic-caused expression of p-Rb, B-Myb, and Bim in vivo as well as in vitro. However, Sertad1 overexpression considerably exacerbated the OGD/R-caused inhibition of cell viability and apoptotic cell dying and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we shown that Sertad1 directly binds to CDK4 and also the CDK4 inhibitor ON123300 restores the results of Sertad1 overexpression on OGD/R-caused apoptotic cell dying and p-Rb, B-Myb, and Bim expression in HT22 cells. These results recommended that Sertad1 led to ischemic/hypoxic nerve injuries by activating the CDK4/p-Rb path.