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学科主题: 药学
题名:
Protosappanin A inhibits oxidative and nitrative stress via interfering the interaction of transmembrane protein CD14 with Toll-like receptor-4 in lipopolysaccharide-induced BV-2 microglia
作者: Zeng, Ke-Wu; Zhao, Ming-Bo; Ma, Zhi-Zhong; Jiang, Yong; Tu, Peng-Fei
关键词: Oxidative stress ; Nitrative stress ; Protosappanin A ; Toll-like receptor 4 ; CD14
刊名: INTERNATIONAL IMMUNOPHARMACOLOGY
发表日期: 2012-12-01
DOI: 10.1016/j.intimp.2012.09.004
卷: 14, 期:4, 页:558-569
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology ; Pharmacology & Pharmacy
研究领域[WOS]: Immunology ; Pharmacology & Pharmacy
关键词[WOS]: NF-KAPPA-B ; ALZHEIMERS-DISEASE ; INNATE IMMUNITY ; CELL-DEATH ; IN-VITRO ; ACTIVATION ; INFLAMMATION ; BRAIN ; NEUROINFLAMMATION ; NEURODEGENERATION
英文摘要:

Oxidative and nitrative stresses have been established to play a pivotal role in neuroinflammation. During inflammation-mediated neurodegenerative diseases, including Alzheimer′s disease and Parkinson′s disease, reactive oxygen species (ROS) and nitric oxide (NO) are produced by activated microglia, further inducing increas.ed neuronal injury in the brain. Protosappanin A (PTA) is a bioactive compound isolated from a traditional Chinese medicine, Caesalpinia sappan L. (Lignum Sappan), showing immunosuppressive effects. However, the molecular mechanisms responsible for the anti-oxidative and nitrative activity of PTA have not been elucidated, particularly in central nervous system. In this study, we found that PTA significantly inhibited ROS and NO production by suppression of NADPH oxidase and inducible nitric oxide synthase (iNOS) activity on lipopolysaccharide (LPS)-stimulated BV-2 microglia. Moreover. PTA modulated IKK/I kappa B/NF-kappa B inflammation signal pathway to inhibit the activity and expressions of NADPH oxidase and iNOS. A further study indicated that PTA didn′t inhibit LPS interaction with transmembrane protein CD14, which is a receptor for LPS binding. However, PTA interfered with the interaction of CD14 with Toll-like receptor (TLR4), an early cell event of IKK/I kappa B/NF-kappa B inflammation signal activation, resulting in a block on LPS translocation from CD14 to TLR4. Therefore, CD14/TLR4 interaction may be a potential drug target in neuroinflammation-related oxidative and nitrative stress. Taken together, these results suggest that PTA has anti-oxidative/nitrative activities on brain immune and neuroinflammation through regulation of CD14/TLR4-dependent IKK/I kappa B/NF-kappa B inflammation signal pathway. (c) 2012 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2012ZX09301002-002-002 ; 30873072 ; 2012M510294
项目资助者: National Key Technology R&amp ; D Program "New Drug Innovation" of China ; Natural Science Foundation of China ; China Postdoctoral Science Foundation ; Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences
WOS记录号: WOS:000313152900028
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52935
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Zeng, Ke-Wu,Zhao, Ming-Bo,Ma, Zhi-Zhong,et al. Protosappanin A inhibits oxidative and nitrative stress via interfering the interaction of transmembrane protein CD14 with Toll-like receptor-4 in lipopolysaccharide-induced BV-2 microglia[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2012,14(4):558-569.
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