Flavonoids Protect Cerebrovascular Endothelial Cells through Nrf2 and PI3K from β-Amyloid Peptide-Induced Oxidative Damage

Author(s): Yuan-Di Xi, Huan-Ling Yu, Juan Ding, Wei-Wei Ma, Lin-Hong Yuan, Jin-Fang Feng, Yi-Xiu Xiao, Rong Xiao.

Journal Name: Current Neurovascular Research

Volume 9 , Issue 1 , 2012

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Abstract:

β-amyloid peptides (Aβ ) induced cerebrovascular dysfunction has been recognized as a vital factor involved in the pathogenesis of neurodegeneration. Genistein, a flavonoid, has antioxidative properties to prevent neurodegeneration induced by β-amyloid peptides. In this study, we were investigating whether genistein could antagonize oxidative damage induced by β-amyloid peptide 25-35 (Aβ25-35) in bEND.3 cells, and also identifying the potential neuroprotective targets of genistein. Vitamin E was used as the positive control. The bEND.3 cells were pre-incubated with/out genistein or vitamin E for 2 h followed by the incubation with 25 μM A 25-35 for another 24 h. The reactive oxygen species (ROS), nitrotyrosine, cell redox state, mRNA or protein expressions of the factors on Nrf2 signaling pathway were measured after Aβ25-35 treatment. The results showed that genistein alleviated the increase of ROS and nitrotyrosine production induced by Aβ25-35, and maintained bEND.3 cell redox state by increasing GSH level and GSH/GSSG. Genistein could reverse the down-regulation of total protein and mRNA expression of NF-E2-related factor 2 (Nrf2), nuclear Nrf2, -γ glutamylcysteine synthetase (γ-GCS), phosphatidylinositol 3-kinase (PI3K) induced by Aβ25-35; while PI3K inhibitor LY294002 could attenuate the activation effects of genistein on Nrf2, especially for the promotion of nuclear translocation. These results suggested that genistein could protect cerebrovascular endothelial cells from Aβ25-35-induced oxidative damage. The potential mechanisms might be associated with the activation of Nrf2 signaling pathway by modulating PI3K activity.

Keywords: Genistein, β-amyloid peptide 25-35, oxidative damage, cerebrovascular endothelial cells, Nrf2 signaling pathway, PI3K, neuroprotection, Alzheimer's disease, neuropathological, cerebrovascular, SIF, flavonoids, antiinflammatory, glial cells, redox, bEND.3

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Article Details

VOLUME: 9
ISSUE: 1
Year: 2012
Page: [32 - 41]
Pages: 10
DOI: 10.2174/156720212799297092
Price: $58

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