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Mol. Cells

Published online January 3, 2022

© The Korean Society for Molecular and Cellular Biology

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

Jianxiong Li1 , Bin Li1 , Yujie Bu1 , Hailin Zhang2,* , Jia Guo1 , Jianping Hu1 , and Yanfang Zhang1

1Department of Neurology, Lanzhou University Second Hospital, Lanzhou 730030, China, 2Neurosurgery, Lanzhou University Second Hospital, Lanzhou 730030, China

Correspondence to : ldyy_zhanghlzhl@lzu.edu.cn

Received: March 25, 2021; Revised: November 19, 2021; Accepted: December 9, 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

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.

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

Article

On-line First

Mol. Cells

Published online January 3, 2022

Copyright © The Korean Society for Molecular and Cellular Biology.

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

Jianxiong Li1 , Bin Li1 , Yujie Bu1 , Hailin Zhang2,* , Jia Guo1 , Jianping Hu1 , and Yanfang Zhang1

1Department of Neurology, Lanzhou University Second Hospital, Lanzhou 730030, China, 2Neurosurgery, Lanzhou University Second Hospital, Lanzhou 730030, China

Correspondence to:ldyy_zhanghlzhl@lzu.edu.cn

Received: March 25, 2021; Revised: November 19, 2021; Accepted: December 9, 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

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.

Keywords: CDK4, neurological injury, oxygen-glucose deprivation/reoxygenation, p-Rb, Sertad1

Mol. Cells
Dec 31, 2021 Vol.44 No.12, pp. 861~919
COVER PICTURE
Structure of the fly peripheral neurons in the fly head. Flies have basic sensory organs including eyes for vision, antennae and maxillary palps for olfaction, and proboscis (magenta) for gustation which can be labelled with monoclonal antibody 22C10. The figure is a 3D reconstructed image with 30 slices of confocal sections with 3 μm interval. It shows that the proboscis is required for sensing attractive carboxylic acids such as glycolic acid, citric acid, and lactic acid (Shrestha and Lee, pp. 900-910).

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