Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related cellular senescence in hippocampus.
Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related cellular senescence in hippocampus.
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Wip1 缺陷引起的 Gamma-H2AX 上调会增加海马中与抑郁相关的细胞衰老
DOI：
10.1038/srep34558
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发表时间：
2016-09-30
影响因子：
4.6
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
He ZY;Wang WY;Hu WY;Yang L;Li Y;Zhang WY;Yang YS;Liu SC;Zhang FL;Mei R;Xing D;Xiao ZC;Zhang M
PP2C家族成员野生型P53诱导的磷酸酶1(Wip1)在应激条件下对DNA损伤反应(DDR)起着重要的调节作用。在本研究中，我们研究了Wip1的表达是否参与了DDR诱导的和抑郁相关的小鼠海马区细胞衰老的调节。我们发现Wip1基因敲除(KO)小鼠海马区细胞衰老和γ-H_2AX活性异常升高，提示Wip1介导的γ-H_2AX去磷酸化缺失促进了海马区细胞衰老。给予抗抑郁药氟西汀对Wip1KO小鼠抑郁样行为增加、细胞衰老加剧和海马区γ-H_2AX活性异常上调无明显影响。野生型C57BL/6小鼠暴露于慢性不可预见性轻度应激后，与对照组相比，海马区细胞衰老和γ-H_2AX活性增加，Wip1表达抑制。在野生型C57BL/6小鼠中给予氟西汀后，随着抑郁样行为的正常化，这些由CUMS引起的症状被有效地预防。我们的数据表明，Wip1介导的γ-H2AX去磷酸化可能在抑郁症相关细胞衰老的发生中发挥重要作用。
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.
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DOI：
10.1186/1478-811x-8-27
发表时间：
2010-09-22
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Freeman AK;Monteiro AN
通讯作者：
Monteiro AN
氟西汀在抑郁样小鼠中以区域依赖性方式调节 mTOR 信号传导。
影响因子：
4.6
作者：
Liu XL;Luo L;Mu RH;Liu BB;Geng D;Liu Q;Yi LT
通讯作者：
Yi LT
影响因子：
5.6
作者：
Barral S;Beltramo R;Salio C;Aimar P;Lossi L;Merighi A
通讯作者：
Merighi A
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
Ca2 通道抑制剂 2-APB 通过阻断 BAX 和 caspase-3 过度激活来逆转海马中 β-淀粉样蛋白诱导的 LTP 缺陷
影响因子：
7.3
作者：
Hu, Wei-Yan;He, Zhi-Yong;Xiao, Zhi-Cheng
通讯作者：
Xiao, Zhi-Cheng