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Icariin inhibits hydrogen peroxide-induced toxicity through inhibition of phosphorylation of JNK/p38 MAPK and p53 activity
Li, Wei-Wei1; Gao, Xiu-Mei2,3,4; Wang, Xue-Mei1; Guo, Hao2,3,4; Zhang, Bo-Li1,2,3,4
关键词Alzheimer&Prime s Disease Oxidative Stress Caspase-3 P53 Dna Oxidation
刊名MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
2011-03-15
DOI10.1016/j.mrfmmm.2010.12.017
708期:1-2页:1-10
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
研究领域[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
关键词[WOS]ACTIVATED PROTEIN-KINASE ; RADIATION-INDUCED APOPTOSIS ; ALZHEIMERS-DISEASE BRAIN ; CYTOCHROME-C RELEASE ; CELL-DEATH ; NEURODEGENERATIVE DISORDERS ; OXIDATIVE DAMAGE ; SIGNAL-TRANSDUCTION ; LIPID-PEROXIDATION ; CANCER CELLS
英文摘要

Oxidative stress caused by hydrogen peroxide (H(2)O(2)) plays an important role in the pathogenesis of Alzheimer′s disease (AD). The prominent damages caused by H(2)O(2) include the ruin of membrane integrity, loss of intracellular neuronal glutathione (GSH), oxidative damage to DNA as well as the subsequent caspase-3 and p53 activation. Icariin is a flavonoid extracted from the traditional Chinese herb Epimedium brevicomum Maxim. We have previously reported that icariin has a good curative effect on patients with mild cognitive impairment (MCI), AD animal and cell models. However, the molecular mechanism of how icariin exerts neuroprotective effects is still not well understood. To address this question, we exposed undifferentiated neuronal cell lines (PC12 cells) to hydrogen peroxide (H(2)O(2)) and investigated the possible neuroprotective mechanisms of icariin. Vitamin E was used as a positive control. We observed that H(2)O(2) activated the JNK/p38 mitogen-activated protein kinase (MAPK) and induced PC12 cells apoptosis in a concentration-dependent manner. More over, we demonstrated that icariin protected PC12 cells by attenuating LDH leakage, reducing GSH depletion, preventing DNA oxidation damage and inhibiting subsequent activation of caspase-3 and p53, which are the main targets of H(2)O(2)-induced cell damage. In addition, we also found that icariin′s neuroprotective effect may partly correlate with its inhibitory effect on JNK/p38 MAPK pathways. Therefore, our findings suggest that icariin is a candidate for a novel neuroprotective drug to against oxidative-stress induced neurodegeneration. (C) 2011 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000289332800001
项目编号30973813 ; 30672760 ; 20070001707 ; 06TXTJJC13600 ; 2005CB523404
资助机构National Natural Science Foundation of China ; Ministry of Education of China ; project of Technology Development Plan of Tianjin ; National Program for Key Basic Research Projects
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50247
专题北京大学第一临床医学院
作者单位1.Peking Univ, Integrated Lab TCM & Western Med, Hosp 1, Beijing 10034, Peoples R China
2.Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med Res, Tianjin 300193, Peoples R China
3.Tianjin Univ Tradit Chinese Med, Key Lab Pharmacol Tradit Chinese Med Formulae, Minist Educ, Tianjin 300193, Peoples R China
4.Tianjin Univ Tradit Chinese Med, Key Lab Traditiona Chinese Med Pharmacol, Tianjin 300193, Peoples R China
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Li, Wei-Wei,Gao, Xiu-Mei,Wang, Xue-Mei,et al. Icariin inhibits hydrogen peroxide-induced toxicity through inhibition of phosphorylation of JNK/p38 MAPK and p53 activity[J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS,2011,708(1-2):1-10.
APA Li, Wei-Wei,Gao, Xiu-Mei,Wang, Xue-Mei,Guo, Hao,&Zhang, Bo-Li.(2011).Icariin inhibits hydrogen peroxide-induced toxicity through inhibition of phosphorylation of JNK/p38 MAPK and p53 activity.MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS,708(1-2),1-10.
MLA Li, Wei-Wei,et al."Icariin inhibits hydrogen peroxide-induced toxicity through inhibition of phosphorylation of JNK/p38 MAPK and p53 activity".MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS 708.1-2(2011):1-10.
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