Hydrogen Sulfide Protects Against Ammonia-Induced Neurotoxicity Through Activation of Nrf2/ARE Signaling in Astrocytic Model of Hepatic Encephalopathy

doi:10.3389/fncel.2020.573422

科研成果详情

题名	Hydrogen Sulfide Protects Against Ammonia-Induced Neurotoxicity Through Activation of Nrf2/ARE Signaling in Astrocytic Model of Hepatic Encephalopathy
作者	Jin, Xiaozhi1; Chen, Dazhi 2; Wu, Faling1; Zhang, Lei 1; Huang, Yu1; Lin, Zhuo1; Wang, Xiaodong 1; Wang, Rui 1; Xu, Lanman 3,4; Chen, Yongping1
发表日期	2020-10-22
发表期刊	FRONTIERS IN CELLULAR NEUROSCIENCE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	hepatic encephalopathy primary astrocytes H2S blood microbiota Nrf2
其他关键词	MITOCHONDRIAL PERMEABILITY TRANSITION ; METHYLMERCURY-INDUCED NEUROTOXICITY ; OXIDATIVE STRESS ; INDUCED CYTOTOXICITY ; CULTURED ASTROCYTES ; REPERFUSION INJURY ; INDUCED APOPTOSIS ; BRAIN ; PATHOGENESIS ; ASSOCIATION
摘要	Objective: Hepatic encephalopathy (HE) characterized by neuropsychiatric abnormalities is a major complication of cirrhosis with high mortality. However, the pathogenesis of HE has not been fully elucidated. This study aimed to determine endogenous hydrogen sulfide (H2S) in the blood of HE patients and investigate the role of H2S in an astrocytic model of HE. Methods: Patients with and without HE were recruited to determine plasma H2S levels and blood microbial 16S rRNA gene. Rat astrocytes were employed as a model of HE by treatment of NH4Cl. Exogenous H2S was preadded. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay, and cell death was evaluated by lactate dehydrogenase (LDH) release. Apoptosis was determined by Hoechst 33342/Propidium Iodide (PI) Double Staining and Western blot analysis of apoptosis-related protein expression. Intracellular reactive oxygen species (ROS) levels were assessed by flow cytometer. Expressions of Nrf2 and its downstream regulated genes were examined by immunofluorescence staining and Western blot, respectively. Nrf2 gene knockdown was performed by antisense shRNA of Nrf2 gene. Results: There was a significant decrease in H2S levels in cirrhotic patients with HE compared with without HE. Blood microbiota analyses revealed that certain strains associated with H2S production were negatively correlated with HE. In vitro, H2S markedly attenuated NH4Cl-induced cytotoxicity, oxidative stress, and apoptosis. This effect was mediated by Nrf2/ARE signaling, and knockdown of Nrf2 expression abolished the antagonistic effect of H2S on NH4Cl-induced neurotoxicity in astrocytes. Conclusion: Levels of H2S and bacteria associated with H2S production are decreased in HE, and H2S functions as the neuroprotector against NH4Cl-induced HE by activating Nrf2/ARE signaling of astrocytes.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770585, 81570514, 81600466]; National Science and Technology Major Project [2017ZX10203201-002-003, 2017ZX10202201, 2018ZX10725506-001]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ17H030005]; Science and Technology Plan Project of Wenzhou, China [ZY2019008]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1662-5102
EISSN	1662-5102
卷号	14 页码:573422
DOI	10.3389/fncel.2020.573422
页数	13
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000585225800001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33192318
PMC记录号	PMC7642620
SCOPUSEID	2-s2.0-85095702792
通讯作者地址	[Chen, Yongping]Department of Infectious Diseases,Wenzhou Key Laboratory of Hepatology,The First Affiliated Hospital of Wenzhou Medical University,Hepatology Institute of Wenzhou Medical University,Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases,Wenzhou,China ; [Xu, Lanman]Department of Infectious Diseases and Liver Diseases,Ningbo Medical Center Lihuili Hospital,Ningbo,China ; [Xu, Lanman]Department of Infectious Diseases and Liver Diseases,The Affiliated Lihuili Hospital of Ningbo University,Ningbo,China
Scopus学科分类	Cellular and Molecular Neuroscience
引用统计	被引频次：6[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/8884
专题	第一临床医学院（信息与工程学院）、附属第一医院_精准医学中心实验室附属第一医院
通讯作者	Xu, Lanman; Chen, Yongping
作者单位	1.Department of Infectious Diseases,Wenzhou Key Laboratory of Hepatology,The First Affiliated Hospital of Wenzhou Medical University,Hepatology Institute of Wenzhou Medical University,Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases,Wenzhou,China; 2.Department of Gastroenterology,The First Hospital of Peking University,Beijing,China; 3.Department of Infectious Diseases and Liver Diseases,Ningbo Medical Center Lihuili Hospital,Ningbo,China; 4.Department of Infectious Diseases and Liver Diseases,The Affiliated Lihuili Hospital of Ningbo University,Ningbo,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Jin, Xiaozhi,Chen, Dazhi,Wu, Faling,et al. Hydrogen Sulfide Protects Against Ammonia-Induced Neurotoxicity Through Activation of Nrf2/ARE Signaling in Astrocytic Model of Hepatic Encephalopathy[J]. FRONTIERS IN CELLULAR NEUROSCIENCE,2020,14:573422.
APA	Jin, Xiaozhi., Chen, Dazhi., Wu, Faling., Zhang, Lei., Huang, Yu., ... & Chen, Yongping. (2020). Hydrogen Sulfide Protects Against Ammonia-Induced Neurotoxicity Through Activation of Nrf2/ARE Signaling in Astrocytic Model of Hepatic Encephalopathy. FRONTIERS IN CELLULAR NEUROSCIENCE, 14, 573422.
MLA	Jin, Xiaozhi,et al."Hydrogen Sulfide Protects Against Ammonia-Induced Neurotoxicity Through Activation of Nrf2/ARE Signaling in Astrocytic Model of Hepatic Encephalopathy".FRONTIERS IN CELLULAR NEUROSCIENCE 14(2020):573422.