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Sulfuretin protects hepatic cells through regulation of ROS levels and autophagic flux
2019-07
发表期刊ACTA PHARMACOLOGICA SINICA (IF:6.9[JCR-2023],7.6[5-Year])
ISSN1671-4083
卷号40期号:7页码:908-918
发表状态已发表
DOI10.1038/s41401-018-0193-5
摘要

Palmitate (PA) exposure induces stress conditions featuring ROS accumulation and upregulation of p62 expression, resulting in autophagic flux blockage and cell apoptosis. Sulfuretin (Sul) is a natural product isolated from Rhus verniciflua Stokes; the cytoprotective effect of Sul on human hepatic L02 cells and mouse primary hepatocytes under PA-induced stress conditions was investigated in this study. Sul induced mitophagy by activation of p-TBK1 and LC3 and produced a concomitant decline in p62 expression. Autophagosome formation and mitophagy were assessed by the sensitive dual fluorescence reporter mCherry-EGFP-LC3B, and mitochondrial fragmentation was analyzed using MitoTracker Deep Red FM. A preliminary structure-activity relationship (SAR) for Sul was also investigated, and the phenolic hydroxyl group was found to be pivotal for maintaining the cytoprotective bioactivity of Sul. Furthermore, experiments using flow cytometry and western blots revealed that Sul reversed the cytotoxic effect stimulated by the autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ), and its cytoprotective effect was almost eliminated when the autophagy-related 5 (Atg5) gene was knocked down. These studies suggest that, in addition to its antioxidative effects, Sul stimulates mitophagy and restores impaired autophagic flux, thus protecting hepatic cells from apoptosis, and that Sul has potential future medical applications for hepatoprotection.

关键词sulfuretin palmitate mitophagy autophagic flux
收录类别SCI ; SCIE ; CSCD
语种英语
资助项目Shanghai Commission of Science and Technology[16JC1405000]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
WOS类目Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号WOS:000472610000005
出版者NATURE PUBLISHING GROUP
WOS关键词OXIDATIVE STRESS ; RHUS-VERNICIFLUA ; HEME OXYGENASE-1 ; FATTY-ACIDS ; MITOCHONDRIAL DYSFUNCTION ; MONITORING AUTOPHAGY ; ACTIVATION ; MECHANISMS ; MITOPHAGY ; APOPTOSIS
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/61152
专题生命科学与技术学院_博士生
生命科学与技术学院_特聘教授组_李佳组
通讯作者Li, Jia; Nan, Fa-jun; Li, Jing-ya
作者单位
1.Chinese Acad Sci, Shanghai Inst Materia Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
第一作者单位生命科学与技术学院
通讯作者单位生命科学与技术学院
推荐引用方式
GB/T 7714
Lu, Yu-ting,Xiao, Yu-feng,Li, Yu-feng,et al. Sulfuretin protects hepatic cells through regulation of ROS levels and autophagic flux[J]. ACTA PHARMACOLOGICA SINICA,2019,40(7):908-918.
APA Lu, Yu-ting,Xiao, Yu-feng,Li, Yu-feng,Li, Jia,Nan, Fa-jun,&Li, Jing-ya.(2019).Sulfuretin protects hepatic cells through regulation of ROS levels and autophagic flux.ACTA PHARMACOLOGICA SINICA,40(7),908-918.
MLA Lu, Yu-ting,et al."Sulfuretin protects hepatic cells through regulation of ROS levels and autophagic flux".ACTA PHARMACOLOGICA SINICA 40.7(2019):908-918.
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