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学科主题: 临床医学
题名:
Hyperoside protects primary rat cortical neurons from neurotoxicity induced by amyloid beta-protein via the PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway
作者: Zeng, Ke-Wu1,2; Wang, Xue-Mei2; Ko, Hyeonseok1; Kwon, Hak Cheol1; Cha, Jin Wook1; Yang, Hyun Ok1
关键词: Neuroprotection ; Amyloid beta-protein (A beta) ; Hyperoside ; PI3K/Akt ; Mitochondria
刊名: EUROPEAN JOURNAL OF PHARMACOLOGY
发表日期: 2011-12-15
DOI: 10.1016/j.ejphar.2011.09.177
卷: 672, 期:1-3, 页:45-55
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: TERT-BUTYL HYDROPEROXIDE ; ALZHEIMERS-DISEASE ; HIPPOCAMPAL-NEURONS ; HYDROGEN-PEROXIDE ; CELL-SURVIVAL ; DYSFUNCTION ; AKT ; ACTIVATION ; TOXICITY ; DAMAGE
英文摘要:

Amyloid beta-protein (A beta), which is deposited in neurons as neurofibrillary tangles, is known to exert cytotoxic effects by inducing mitochondrial dysfunction. Additionally, the PI3K/Akt-mediated interaction between Bad and Bcl(XL) plays an important role in maintaining mitochondrial integrity. However, the application of therapeutic drugs, especially natural products in Alzheimer′s disease therapy via PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway has not aroused extensive attention. In the present study, we investigated the neuroprotective effects of hyperoside, a bioactive flavonoid compound from Hypericum perforatum, on A beta(25-35)-induced primary cultured cortical neurons, and also examined the potential cellular signaling mechanism for A beta detoxication. Our results showed that treatment with hyperoside significantly inhibited A beta(25-35)-induced cytotoxicity and apoptosis by reversing A beta-induced mitochondrial dysfunction, including mitochondrial membrane potential decrease, reactive oxygen species production, and mitochondrial release of cytochrome c. Further study indicated that hyperoside can activate the PI3K/Akt signaling pathway, resulting in inhibition of the interaction between Bad and Bcl(XL), without effects on the interaction between Bad and Bcl-2. Furthermore, hyperoside inhibited mitochondria-dependent downstream caspase-mediated apoptotic pathway, such as that involving caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP). These results demonstrate that hyperoside can protect AB-induced primary cultured cortical neurons via PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway, and they raise the possibility that hyperoside could be developed into a clinically valuable treatment for Alzheimer′s disease and other neuronal degenerative diseases associated with mitochondrial dysfunction. (C) 2011 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2Z03401 ; 2Z03380 ; 2U04150 ; 30973813 ; 30672760 ; 20070001707
项目资助者: Korea Institute of Science and Technology, Republic of Korea ; National Natural Science Fund of China ; Ministry of Education, China
WOS记录号: WOS:000298202700006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51443
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Beijing 100034, Peoples R China
2.Korea Inst Sci & Technol, Nat Prod Res Ctr, Gangneung Inst, Kangnung 210340, South Korea

Recommended Citation:
Zeng, Ke-Wu,Wang, Xue-Mei,Ko, Hyeonseok,et al. Hyperoside protects primary rat cortical neurons from neurotoxicity induced by amyloid beta-protein via the PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2011,672(1-3):45-55.
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