Miltirone protects human EA.hy926 endothelial cells from oxidized low-density lipoprotein-derived oxidative stress via a heme oxygenase-1 and MAPK/Nrf2 dependent pathway
文献类型：期刊论文
| 作者 | Zhang, Liu1; Zhang, Hui1; Li, Xueyan1; Jia, Bingjie1; Yang, Yuyu1; Zhou, Ping1; Li, Ping1; Chen, Jun1,2 |
| 刊名 | PHYTOMEDICINE
 |
| 出版日期 | 2016-12-15 |
| 卷号 | 23期号:14页码:1806-1813 |
| 关键词 | Miltirone Nrf2 HO-1 Endothelial dysfunction Oxidative stress |
| ISSN号 | 0944-7113 |
| DOI | 10.1016/j.phymed.2016.11.003 |
| 文献子类 | Article |
| 英文摘要 | Background: Oxidized low-density lipoprotein (ox-LDL) is an underlying cause of endothelial dysfunction, which is an early event in the pathogenesis of atherosclerosis. In our previous study, we established an ARE-driven luciferase reporter system and screened out several potential Nrf2 activators from Salvia miltiorrhiza Bunge. Purpose: Since miltirone showed the most potent ARE-driven luciferase activity, the aim of this study was to test the protective role of miltirone against oxidative stress in endothelial cell and to investigate the underlying mechanistic signaling pathways. Study Design/Method: In the present study, miltirone increased the expression of nuclear translocation and transcriptional activities of NF-E2-related factor 2 (Nrf2), which led to augmented expression of antioxidant-response element (ARE)-dependent heme oxygenase-1 (HO-1) and NAD(P) H-quinone oxidoreductase 1 (NQO1). Inhibition of Nrf2/HO-1 by RNA interference abolished miltirone-induced cytoprotective effects against ox-LDL, which suggested that Nrf2 and the downstream expression of HO-1 are required for the functional effects of miltirone. Ox-LDL-stimulated mitogen-activated protein kinase activation, ROS production, and miltirone dramatically inhibited synthesis of ROS, as well as decreased SOD and glutathione S-transferase (GST) in human EA. hy926 endothelial cells. Results: Miltirone-induced Nrf2 and HO-1 expression was related to mitogen-activated protein kinase (MAPK) pathways. The activation of MAPK was partially dependent on the phosphorylation of the cJun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways, but not P38 MAPK signaling. However, miltirone-induced Nrf2/HO-1 expression can only be effectively blocked by JNK inhibitor SP600125. Conclusion: Our findings reveal that miltirone exerts protective functions on endothelial cells in response to ox-LDL-induced oxidative stress, and does so via Nrf2/HO-1, which provides novel insights into the antioxidant capacity of miltirone. (C) 2016 Elsevier GmbH. All rights reserved. |
| WOS关键词 | UP-REGULATION ; EXPRESSION ; ATHEROSCLEROSIS ; ACTIVATION ; NRF2 ; ERK ; DISEASE ; RECEPTOR-1 ; INDUCTION ; MECHANISM |
| 资助项目 | National Scientific Foundation of China[81421005] ; National Scientific Foundation of China[81573705] ; Fundamental Research Funds for the Central Universities[2015PY008] ; State Key Laboratory of Drug Research[SIMM1501KF-04] ; Priority Academic Program Development of Jiangsu Higher Education Institutions[00000000] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000389207800013 |
| 出版者 | ELSEVIER GMBH, URBAN & FISCHER VERLAG |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275763]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Li, Ping; Chen, Jun |
| 作者单位 | 1.China Pharmaceut Univ, State Key Lab Nat Med, 24 Tongjia Lane, Nanjing 210009, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Liu,Zhang, Hui,Li, Xueyan,et al. Miltirone protects human EA.hy926 endothelial cells from oxidized low-density lipoprotein-derived oxidative stress via a heme oxygenase-1 and MAPK/Nrf2 dependent pathway[J]. PHYTOMEDICINE,2016,23(14):1806-1813. |
| APA | Zhang, Liu.,Zhang, Hui.,Li, Xueyan.,Jia, Bingjie.,Yang, Yuyu.,...&Chen, Jun.(2016).Miltirone protects human EA.hy926 endothelial cells from oxidized low-density lipoprotein-derived oxidative stress via a heme oxygenase-1 and MAPK/Nrf2 dependent pathway.PHYTOMEDICINE,23(14),1806-1813. |
| MLA | Zhang, Liu,et al."Miltirone protects human EA.hy926 endothelial cells from oxidized low-density lipoprotein-derived oxidative stress via a heme oxygenase-1 and MAPK/Nrf2 dependent pathway".PHYTOMEDICINE 23.14(2016):1806-1813. |
入库方式： OAI收割
来源：上海药物研究所
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