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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Keap1 as Target of Genistein on Nrf2 Signaling Pathway Antagonizing Aβ induced Oxidative Damage of Cerebrovascular Endothelial Cells

Author(s): Yuan-Di Xi, Xiao-Ying Li, Ya-Fei Chi, Jing Han, Hong-Rui Li, Xian-Yun Wang, Xuan Wang, Tian-Tian Li, Hui-Yan Yu and Rong Xiao*

Volume 19, Issue 1, 2022

Published on: 15 June, 2022

Page: [73 - 82] Pages: 10

DOI: 10.2174/1567202619666220406100320

Price: $65

Abstract

Background: β-amyloid peptides (Aβ) induced oxidative damage contributes to the pathogenesis of neurodegenerative diseases, and the cerebrovascular system is more vulnerable to oxidative stress. Our earlier study showed a clue that Genistein (Gen) might activate the Nf-E2 related factor 2 (Nrf2) pathway to protect cerebrovascular cells from oxidative damage induced by Aβ, but the specific mechanisms and regulation targets are unclear.

Objective: In this study, the anti-oxidative effects and the possible targets of Gen on regulating the Nrf2 pathway in bEnd.3 cells were investigated. Cells were divided into control, Aβ25-35, Gen, and Gen+Aβ25-35 groups.

Methods: Cell viability, levels of malondialdehyde (MDA), Superoxide Dismutase (SOD) activity, and nitrotyrosine were evaluated. Moreover, mRNA and/or protein expressions of Nrf2 and kelchlike ECH-associated protein 1 (Keap1) were measured. Then we transfected Keap1 over-expressed plasmid into bEnd.3 cells and measured the protein expressions of Nrf2 pathway related factors.

Results: Data showed that Gen could inhibit the over-production of MDA and nitrotyrosine and activate SOD activity. Furthermore, we discovered that Gen could up-regulate Nrf2 mRNA and protein expression while down-regulating Keap1 protein expression. The Keap1 over-expressed plasmid study revealed that the up-regulation of Nrf2 protein expression induced by Gen pretreatment could be blocked by transfection of Keap1 over-expressed plasmid, and the same results were observed in Nrf2 downstream factors.

Conclusion: Gen could alleviate the cerebrovascular cells' oxidative damage induced by Aβ25-35 by regulating the Nrf2 pathway, and Keap1 might be one of the targets of Gen in activating the Nrf2 pathway.

Keywords: Genistein, β-amyloid peptides 25-35, cerebrovascular endothelial cell, Keap1, Nrf2, oxidative damage.

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