Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related cellular senescence in hippocampus

Zhi-Yong He, Wenyue Wang, Wei-Yan Hu, Lu Yang, Yan Li, Wei-Yuan Zhang, Ya-Shu Yang, Si-Cheng Liu, Feng-Lan Zhang, Rong Mei, Da Xing, Zhi-Cheng Xiao, Ming Zhang

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically regulates DNA damage response (DDR) under stressful situations. In the present study, we investigated whether Wip1 expression was involved in the regulation of DDR-induced and depression-related cellular senescence in mouse hippocampus. We found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal cellular senescence and of γ-H2AX activity, which is known as a biomarker of DDR and cellular senescence, indicating that the lack of Wip1-mediated γ-H2AX dephosphorylation facilitates cellular senescence in hippocampus. Administration of the antidepressant fluoxetine had no significant effects on the increased depression-like behaviors, enriched cellular senescence, and aberrantly upregulated hippocampal γ-H2AX activity in Wip1 KO mice. After wildtype C57BL/6 mice were exposed to the procedure of chronic unpredictable mild stress (CUMS), cellular senescence and γ-H2AX activity in hippocampus were also elevated, accompanied by the suppression of Wip1 expression in hippocampus when compared to the control group without CUMS experience. These CUMS-induced symptoms were effectively prevented following fluoxetine administration in wildtype C57BL/6 mice, with the normalization of depression-like behaviors. Our data demonstrate that Wip1-mediated γ-H2AX dephosphorylation may play an important role in the occurrence of depression-related cellular senescence.
Original languageEnglish
Article number34558
Number of pages11
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 30 Sep 2016

Cite this

He, Zhi-Yong ; Wang, Wenyue ; Hu, Wei-Yan ; Yang, Lu ; Li, Yan ; Zhang, Wei-Yuan ; Yang, Ya-Shu ; Liu, Si-Cheng ; Zhang, Feng-Lan ; Mei, Rong ; Xing, Da ; Xiao, Zhi-Cheng ; Zhang, Ming. / Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related cellular senescence in hippocampus. In: Scientific Reports. 2016 ; Vol. 6.
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abstract = "The PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically regulates DNA damage response (DDR) under stressful situations. In the present study, we investigated whether Wip1 expression was involved in the regulation of DDR-induced and depression-related cellular senescence in mouse hippocampus. We found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal cellular senescence and of γ-H2AX activity, which is known as a biomarker of DDR and cellular senescence, indicating that the lack of Wip1-mediated γ-H2AX dephosphorylation facilitates cellular senescence in hippocampus. Administration of the antidepressant fluoxetine had no significant effects on the increased depression-like behaviors, enriched cellular senescence, and aberrantly upregulated hippocampal γ-H2AX activity in Wip1 KO mice. After wildtype C57BL/6 mice were exposed to the procedure of chronic unpredictable mild stress (CUMS), cellular senescence and γ-H2AX activity in hippocampus were also elevated, accompanied by the suppression of Wip1 expression in hippocampus when compared to the control group without CUMS experience. These CUMS-induced symptoms were effectively prevented following fluoxetine administration in wildtype C57BL/6 mice, with the normalization of depression-like behaviors. Our data demonstrate that Wip1-mediated γ-H2AX dephosphorylation may play an important role in the occurrence of depression-related cellular senescence.",
author = "Zhi-Yong He and Wenyue Wang and Wei-Yan Hu and Lu Yang and Yan Li and Wei-Yuan Zhang and Ya-Shu Yang and Si-Cheng Liu and Feng-Lan Zhang and Rong Mei and Da Xing and Zhi-Cheng Xiao and Ming Zhang",
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Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related cellular senescence in hippocampus. / He, Zhi-Yong; Wang, Wenyue; Hu, Wei-Yan; Yang, Lu; Li, Yan; Zhang, Wei-Yuan; Yang, Ya-Shu; Liu, Si-Cheng; Zhang, Feng-Lan; Mei, Rong; Xing, Da; Xiao, Zhi-Cheng; Zhang, Ming.

In: Scientific Reports, Vol. 6, 34558, 30.09.2016.

Research output: Contribution to journalArticleResearchpeer-review

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AU - He, Zhi-Yong

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AU - Li, Yan

AU - Zhang, Wei-Yuan

AU - Yang, Ya-Shu

AU - Liu, Si-Cheng

AU - Zhang, Feng-Lan

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AU - Xing, Da

AU - Xiao, Zhi-Cheng

AU - Zhang, Ming

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