Sulfuretin protects hepatic cells through regulation of ROS levels and autophagic flux
文献类型：期刊论文
| 作者 | Lu, Yu-Ting; Xiao, Yu-Feng; Li, Yu-Feng; Li, Jia ; Nan, Fa-Jun; Li, Jing-Ya
|
| 刊名 | Acta pharmacologica Sinica
 |
| 出版日期 | 2018-12-18 |
| ISSN号 | 1745-7254 |
| DOI | 10.1038/s41401-018-0193-5 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266323]  |
| 专题 | 新药研究国家重点实验室 药物安全性评价中心 国家新药筛选中心 |
| 通讯作者 | Li, Jia; Nan, Fa-Jun; Li, Jing-Ya |
| 作者单位 | State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China |
| 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,2018. |
| APA | Lu, Yu-Ting,Xiao, Yu-Feng,Li, Yu-Feng,Li, Jia,Nan, Fa-Jun,&Li, Jing-Ya.(2018).Sulfuretin protects hepatic cells through regulation of ROS levels and autophagic flux.Acta pharmacologica Sinica. |
| MLA | Lu, Yu-Ting,et al."Sulfuretin protects hepatic cells through regulation of ROS levels and autophagic flux".Acta pharmacologica Sinica (2018). |
入库方式： OAI收割
来源：上海药物研究所
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