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Hypoxia preconditioning increases Notch1 activity by regulating DNA methylation in vitro and in vivo

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收录情况： ◇ SCIE

作者：
Zhehan Chang[1,2,3] * ; Qi Liu[4] * ; Peijia Fan[5] ; Wenqiang Xu[2,3] ; Yabin Xie[2,3] ; Kerui Gong[6] ; Chunyang Zhang[7] ; Zhijun Zhao[7] ; Kai Sun[1] ; Guo Shao[1,2,3,7,8] ;
机构： [1]Center for Translational Medicine, The Third People’s Hospital of Longgang District, Shenzhen, China [2]Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College, Baotou, China [3]Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China [4]Department of Radiology, The Second Afliated Hospital of Baotou Medical College, Baotou, China [5]Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China [6]Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, USA [7]Department of Neurosurgery, The First Afliated Hospital of Baotou Medical College, Baotou, China [8]Joint Laboratory of South China Hospital Afliated to Shenzhen University and Third People’s Hospital of Longgang District, Shenzhen University, Shenzhen, China
出处：
DOI： 10.1007/s11033-024-09308-9
ISSN：

关键词： Hypoxic preconditioning  Neurogenesis  Notch1  Learning and memory  DNA methylation

摘要：
Our previous research has demonstrated that hypoxic preconditioning (HPC) can improve spatial learning and memory abilities in adult mice. Adult hippocampal neurogenesis has been associated with learning and memory. The Neurogenic locus notch homolog protein (Notch) was involved in adult hippocampal neurogenesis, as well as in learning and memory. It is currently unclear whether the Notch pathway regulates hippocampal neuroregeneration by modifying the DNA methylation status of the Notch gene following HPC.The HPC animal model and cell model were established through repeated hypoxia exposure using mice and the mouse hippocampal neuronal cell line HT22. Step-down test was conducted on HPC mice. Real-time PCR and Western blot analysis were used to assess the mRNA and protein expression levels of Notch1 and hairy and enhancer of split1 (HES1). The presence of BrdU-positive cells and Notch1 expression in the hippocampal dental gyrus (DG) were examined with confocal microscopy. The methylation status of the Notch1 was analyzed using methylation-specific PCR (MS-PCR). HT22 cells were employed to elucidate the impact of HPC on Notch1 in vitro.HPC significantly improved the step-down test performance of mice with elevated levels of mRNA and protein expression of Notch1 and HES1 (P < 0.05). The intensities of the Notch1 signal in the control group, the H group and the HPC group were 2.62 ± 0.57 × 107, 2.87 ± 0.84 × 107, and 3.32 ± 0.14 × 107, respectively, and the number of BrdU (+) cells in the hippocampal DG were 1.83 ± 0.54, 3.71 ± 0.64, and 7.29 ± 0.68 respectively. Compared with that in C and H group, the intensity of the Notch1 signal and the number of BrdU (+) cells increased significantly in HPC group (P < 0.05). The methylation levels of the Notch1 promoter 0.82 ± 0.03, 0.65 ± 0.03, and 0.60 ± 0.02 in the C, H, and HPC groups, respectively. The methylation levels of Notch1 decreased significantly (P < 0.05). The effect of HPC on HT22 cells exhibited similarities to that observed in the hippocampus.HPC may confer neuroprotection by activating the Notch1 signaling pathway and regulating its methylation level, resulting in the regeneration of hippocampal neurons.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.

基金：
This work was funded by grants from the National Natural Science Foundation of China (Nos.81660307, 82060337), the Shenzhen Longgang District Economic and Technological Development Special Fund Medical, Health Technology Plan Project (Nos.LGKCYLWS2021000033, LGKCYLWS2023025), the Shenzhen Science and Technology Plan Project (Nos.JCYJ20220531092412028, JCYJ20230807121306012), the Inner Mongolia Science Foundation (Nos. 2020MS0810, 2021LHMS08021 and 2021LHMS08022).
语种：
外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 4 区 生物学
小类 | 4 区 生化与分子生物学
最新[2023]版：
大类 | 4 区 生物学
小类 | 4 区 生化与分子生物学
JCR分区：
出版当年[2022]版：
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版：
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]Center for Translational Medicine, The Third People’s Hospital of Longgang District, Shenzhen, China [2]Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College, Baotou, China [3]Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
共同第一作者：
通讯作者：
通讯机构： [1]Center for Translational Medicine, The Third People’s Hospital of Longgang District, Shenzhen, China [2]Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College, Baotou, China [3]Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China [7]Department of Neurosurgery, The First Afliated Hospital of Baotou Medical College, Baotou, China [8]Joint Laboratory of South China Hospital Afliated to Shenzhen University and Third People’s Hospital of Longgang District, Shenzhen University, Shenzhen, China
推荐引用方式(GB/T 7714)：
Zhehan Chang,Qi Liu,Peijia Fan,et al.Hypoxia preconditioning increases Notch1 activity by regulating DNA methylation in vitro and in vivo[J].Molecular Biology Reports.2024,51(1):507.doi:10.1007/s11033-024-09308-9.
APA：
Zhehan Chang,Qi Liu,Peijia Fan,Wenqiang Xu,Yabin Xie...&Guo Shao.(2024).Hypoxia preconditioning increases Notch1 activity by regulating DNA methylation in vitro and in vivo.Molecular Biology Reports,51,(1)
MLA：
Zhehan Chang,et al."Hypoxia preconditioning increases Notch1 activity by regulating DNA methylation in vitro and in vivo".Molecular Biology Reports 51..1(2024):507

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