检索结果-南通市图书馆

High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NrF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NrF2

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Dual roles of p62/SQSTM1 in the injury and recovery phases of acetaminophen-induced liver injury in mice

引用

Acta Pharmaceutica Sinica B 2021年第12期11卷 3791-3805页

作者： Hui Qian Qingyun Bai Xiao Yang Jephte Y.Akakpo Lili Ji Li Yang Thomas rulicke Kurt Zatloukal Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA The MOE Key Laboratory for Standardization of Chinese Medicines Shanghai Key Laboratory of Compound Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China School of Chemistry and Bioengineering Yichun UniversityYichun 336000China Department of Biomedical Sciences University of Veterinary Medicine Vienna Veterina¨rplatzVienna 1210Austria The Institute of Pathology Medical University of GrazGraz A-8036Austria

Acetaminophen(APAP)overdose can induce liver injury and is the most frequent cause of acute liver failure in the United *** investigated the role of p62/SQSTM1(referred to as p62)in APAP-induced liver injury(AILI)in *** found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment,which was inversely correlated with the hepatic levels of *** also activated mTOr at 24 h,which is associated with increased cell *** contrast,p62 knockout(KO)mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOr activation and cell proliferation with aggravated liver injury at 24 h after APAP ***,p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 *** found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor(VWF)and platelet aggregation,which are associated with increased cell proliferation and improved liver injury at 48 h after APAP *** data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.

关键词： Autophagy Coagulation DILI Liver regeneration Macrophage Hepatotoxicity Platelet

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

A fluorescence imaging based-assay to monitor mitophagy in cultured hepatocytes and mouse liver

引用

Liver research 2021年第1期5卷 16-20页

作者： Xiaowen Ma Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsThe University of Kansas Medical CenterKansas CityKSUSA

Background and aim Mitophagy is a lysosomal degradation pathway that selectively removes damaged,aged and dysfunctional *** advances in understanding mitophagy highlight its importance in various physiological and pathological conditions including liver ***,reliable quantitative assays to monitor mitophagy in cultured cells and in tissues are still *** We describe a detailed protocol for monitoring mitophagy in primary cultured hepatocytes and mouse livers using cytochrome C oxidase subunit 8(Cox8)-enhanced green fluorescent protein(EGFP)-mCherry,a dual color fluorescence based-imaging *** Mitochondria are visualized in yellow fluorescence due to the merged EGFP and mCherry *** contrast,autolysosome enclosed mitochondria are shown as red puncta due to quenching of EGFP green fluorescence in acidic *** the number of red-only puncta in each cell can obtain a quantitative measure for *** Cox8-EGFP-mCherry assay can specifically target to mitochondria and be used to monitor mitophagy in vitro and in vivo.

关键词： Autophagy Cox8-EGFP-mCherry Fluorescence microscopy Mitochondria Lysosome

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Alcohol and drug-induced liver injury:Metabolism,mechanisms,pathogenesis and potential therapies

引用

Liver research 2019年第3期3卷 129-131页

作者： Wen-Xing Ding Li Yang Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKSUSA Institute of Chinese Materia Medica Shanghai University of Traditional Chinese MedicineShanghaiChina

The liver is one of the major metabolic organs in the body,playing a critical role in the metabolism of carbohydrates,proteins,amino acids,lipids,drugs and *** a result,the liver often becomes the target of drug and xenobiotics-induced ***,the most common cause for acute liver failure in the United States and multiple European countries is drug-induced liver injury(DILI).This is one of the leading causes for halting drug development and removing drugs from the consumer market.

关键词： drugs metabolism organs

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：