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学科主题: 基础医学
题名:
Formononetin Protects Neurons Against Hypoxia-Induced Cytotoxicity Through Upregulation of ADAM10 and sA beta PP alpha
作者: Sun, Miao1,2,3; Zhou, Ting1,2,3; Zhou, Liang1,2,3; Chen, Qiang4; Yu, Yan1,2,3; Yang, Huan1,2,3; Zhong, Kaiyin1,2,3; Zhang, Ximeng1,2,3; Xu, Feng5; Cai, Shaoqing5; Yu, Albert1,2,3; Zhang, Hui6; Xiao, Ruizhong6; Xiao, Dongsheng6; Chui, Dehua1,2,3,6
关键词: ADAM10 ; amyloid-beta protein precursor (A beta PP) ; formononetin ; soluble-A beta PP alpha
刊名: JOURNAL OF ALZHEIMERS DISEASE
发表日期: 2012
DOI: 10.3233/JAD-2011-110506
卷: 28, 期:4, 页:795-808
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: AMYLOID-PRECURSOR PROTEIN ; HUMAN NEUROBLASTOMA SH-SY5Y ; HEPARIN-BINDING DOMAIN ; ALZHEIMERS-DISEASE ; TRIFOLIUM-PRATENSE ; CEREBRAL-ISCHEMIA ; CORTICAL-NEURONS ; OXIDATIVE STRESS ; ASTRAGALUS-MONGHOLICUS ; CASPASE-3 ACTIVATION
英文摘要:

Formononetin, an active constituent of the Chinese herb Astragali Radix, has been reported to have beneficial effects for Alzheimer′s disease (AD). Yet the mechanism of this effect remains to be elucidated. The present study shows that formononetin increases soluble-A beta PP alpha (sA beta PP alpha) secretion and thus protects human-A beta PP Swedish mutation cell (N2a-A beta PP cell) from hypoxia- induced apoptosis. Using hypoxic N2a-A beta PP cell as an in vitro model of AD- like pathology, we confirmed that regular treatment with formononetin could have neuroprotective effects, followed respectively by reduced caspase 3 activity and increased cell viability. Strikingly, our data revealed that the caspase 3- blocking effect of formononetin was largely mediated by stimulation of alpha-secretase cleavage of A beta PP, and increasing the secretion of its soluble form, sA beta PP alpha. Moreover, the protective effect of formononetin was totally inhibited by TAPI-2, an alpha-secretase complex inhibitor, suggesting the role of the sA beta PP alpha pathway in the neuroprotective response to formononetin. We also found that the stimulative effect of formononetin on alpha -secretase activity was mainly conducted by upregulating ADAM10 expression at the transcriptional level. Altogether, our study provides novel insights into how formononetin mediates stimulation of the ADAM10-sA beta PP alpha pathway and exerts a neuronal protective effect.

语种: 英语
所属项目编号: 30670414 ; 30830120 ; 30973145 ; 81171015 ; 20090001110058 ; 2012CB911004
项目资助者: National Natural Science Foundation of China (NSFC) ; Doctoral Fund of Ministry of Education ; National High Technology Research and Development Program of China (973 Program)
WOS记录号: WOS:000300715600006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65791
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Minist Educ, Beijing 100191, Peoples R China
2.Peking Univ, Key Lab Neurosci, Dept Neurobiol, Hlth Sci Ctr,Minist Educ, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Minist Publ Hlth, Beijing 100191, Peoples R China
4.Ningbo Beilun Hosp, Dept Neurol, Ningbo 315806, Peoples R China
5.Peking Univ, Sch Pharmaceut Sci, Dept Nat Med, Beijing 100191, Peoples R China
6.Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China

Recommended Citation:
Sun, Miao,Zhou, Ting,Zhou, Liang,et al. Formononetin Protects Neurons Against Hypoxia-Induced Cytotoxicity Through Upregulation of ADAM10 and sA beta PP alpha[J]. JOURNAL OF ALZHEIMERS DISEASE,2012,28(4):795-808.
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