Role of Ero1α in cognitive impairment induced by chronic hypoxia.

doi:10.1016/j.brainres.2022.148117

科研成果详情

题名	Role of Ero1α in cognitive impairment induced by chronic hypoxia.
作者	Zhang, Nan1; Shentu, Yangping 2; Zhu, Min1; Wang, Hui1; Yin, Xianghong1; Du, Congkuo1; Xue, Feng1; Fan, Junming1; Gong, Yongsheng3; Fan, Xiaofang4
发表日期	2022-10-08
发表期刊	Brain research 影响因子和分区
语种	英语
关键词	Cognitive impairment Endoplasmic reticulum stress Ero1α Hypoxia Neuronal apoptosis
摘要	Recent reports suggested the endoplasmic reticulum stress (ERS)-associated pathway is involved with cognitive impairment in hypoxia condition. ERO1-like protein alpha (Ero1α), an endoplasmic reticulum membrane-bound N-glycoprotein, has been reported to promote oxidative protein folding. However, no studies have reported whether the Ero1α is trapped in hypoxia-induced neuronal loss through the ERS-associated pathways. In our study, this effect of Ero1α was investigated using C57BL/6J mice, the HT22 cells and primary rat neurons. C57BL/6J mice were modeled in a hypoxic chamber for 4 weeks. Behavioral tests were then carried out to test cognitive functions, including the Morris water maze and fear conditioning test. Proteomics showed that Ero1α distinctly upregulated compared with normoxia group and verified using western blotting. Flow cytometry and immunofluorescence were used to analyze the neuroprotective effect of inhibitor EN460 of Ero1α in the HT22 cells. In C57BL/6J mice, hypoxia significantly caused cognitive decline. Brain slice staining results were also used to confirm this effect. Western blot analysis demonstrated that Ero1α, ERS-associated proteins and apoptosis-associated proteins significantly increased in the hypoxia treated groups, further proliferation-related marker protein decreased. EN460, a selective endoplasmic reticulum oxidation 1 (ERO1) inhibitor, counteracted neuronal apoptosis and ameliorated neuronal cell proliferation in the HT22 cells. Taken together, our data indicate that hypoxia induces cognitive impairment, at least in part, by upregulating Ero1α which contributes to neuronal apoptosis through ERS signaling pathway, providing preliminary experimental evidence that the Ero1α is a promising therapeutic target in hypoxia-induced cognitive deficits.
ISSN	0006-8993
卷号	1797 页码:148117
DOI	10.1016/j.brainres.2022.148117
收录类别	PUBMED
URL	查看原文
PubMed ID	36220374
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/166878
专题	基础医学院（机能实验教学中心）附属第一医院_病理科
作者单位	1.Institute of Hypoxia Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.; 2.Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.; 3.Institute of Hypoxia Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: fxbgong@126.com.; 4.Institute of Hypoxia Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: fxbwzmc@126.com.
第一作者单位	基础医学院（机能实验教学中心）
第一作者的第一单位	基础医学院（机能实验教学中心）
推荐引用方式 GB/T 7714	Zhang, Nan,Shentu, Yangping,Zhu, Min,et al. Role of Ero1α in cognitive impairment induced by chronic hypoxia.[J]. Brain research,2022,1797:148117.
APA	Zhang, Nan., Shentu, Yangping., Zhu, Min., Wang, Hui., Yin, Xianghong., ... & Fan, Xiaofang. (2022). Role of Ero1α in cognitive impairment induced by chronic hypoxia.. Brain research, 1797, 148117.
MLA	Zhang, Nan,et al."Role of Ero1α in cognitive impairment induced by chronic hypoxia.".Brain research 1797(2022):148117.