Role of Ero1 alpha in cognitive impairment induced by chronic hypoxia

doi:10.1016/j.brainres.2022.148117

科研成果详情

题名	Role of Ero1 alpha in cognitive impairment induced by chronic hypoxia
作者	Zhang, Nan1; Shentu, Yangping 2; Zhu, Min1; Wang, Hui 1; Yin, Xianghong1; Du, Congkuo1; Xue, Feng 1; Fan, Junming1; Gong, Yongsheng1; Fan, Xiaofang1
发表日期	2022-12-15
发表期刊	Brain research 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Hypoxia Cognitive impairment Ero1? Endoplasmic reticulum stress Neuronal apoptosis
其他关键词	ENDOPLASMIC-RETICULUM STRESS ; APOPTOSIS ; EXPRESSION ; DAMAGE ; CELLS
摘要	Recent reports suggested the endoplasmic reticulum stress (ERS)-associated pathway is involved with cognitive impairment in hypoxia condition. ERO1-like protein alpha (Ero1 alpha), an endoplasmic reticulum membrane-bound N-glycoprotein, has been reported to promote oxidative protein folding. However, no studies have reported whether the Ero1 alpha is trapped in hypoxia-induced neuronal loss through the ERS-associated pathways. In our study, this effect of Ero1 alpha 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 Ero1 alpha 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 Ero1 alpha 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 Ero1 alpha, 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 Ero1 alpha which contributes to neuronal apoptosis through ERS signaling pathway, providing preliminary experimental evidence that the Ero1 alpha is a promising therapeutic target in hypoxia-induced cognitive deficits.
资助项目	Wenzhou Municipal Science and Technology Bureau of China [Y20210079]
出版者	ELSEVIER
出版地	AMSTERDAM
ISSN	0006-8993
EISSN	1872-6240
卷号	1797
DOI	10.1016/j.brainres.2022.148117
页数	10
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000895706700001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	36220374
SCOPUSEID	2-s2.0-85139838935
通讯作者地址	[Gong, Yongsheng]Institute of Hypoxia Medicine,School of Basic Medical Sciences,Chashan Higher Education Zone,Ouhai District,Wenzhou,325006,China
Scopus学科分类	Neuroscience (all);Molecular Biology;Neurology (clinical);Developmental Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/172110
专题	基础医学院（机能实验教学中心）附属第一医院
通讯作者	Gong, Yongsheng
作者单位	1.Institute of Hypoxia Medicine,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Department of Pathology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China
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 Ero1 alpha in cognitive impairment induced by chronic hypoxia[J]. Brain research,2022,1797.
APA	Zhang, Nan., Shentu, Yangping., Zhu, Min., Wang, Hui., Yin, Xianghong., ... & Fan, Xiaofang. (2022). Role of Ero1 alpha in cognitive impairment induced by chronic hypoxia. Brain research, 1797.
MLA	Zhang, Nan,et al."Role of Ero1 alpha in cognitive impairment induced by chronic hypoxia".Brain research 1797(2022).