View : 141 Download: 0

Antioxidant mechanism of isoflavone metabolites in hydrogen peroxide-stimulated rat primary astrocytes: Critical role of hemeoxygenase-1 and NQO1 expression

Title
Antioxidant mechanism of isoflavone metabolites in hydrogen peroxide-stimulated rat primary astrocytes: Critical role of hemeoxygenase-1 and NQO1 expression
Authors
Park J.-S.Jung J.-S.Jeong Y.-H.Hyun J.-W.Le T.K.V.Kim D.-H.Choi E.-C.Kim H.-S.
Ewha Authors
김희선박진선
SCOPUS Author ID
김희선scopus; 박진선scopus
Issue Date
2011
Journal Title
Journal of Neurochemistry
ISSN
0022-3042JCR Link
Citation
vol. 119, no. 5, pp. 909 - 919
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The brain is highly vulnerable to oxidative stress, thus controlling oxidative stress is considered to be an important therapeutic target for neurodegenerative diseases. In this study, we found that two isoflavone metabolites (tectorigenin and glycitein) inhibited hydrogen peroxide-induced reactive oxygen species (ROS) generation and subsequent cell death in rat primary astrocytes. The isoflavone metabolites increased the expression of phase II antioxidant enzymes, such as hemeoxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), and pre-treatment of cells with their specific inhibitors or small interfering RNA (siRNA) reversed the antioxidant and cytoprotective effects of isoflavones. The results suggest that the antioxidant/cytoprotective effects of isoflavone metabolites are at least because of increased HO-1 and NQO1 expression. Further mechanistic studies revealed that isoflavones increase the binding of transcription factors [nuclear factor-E2-related factor 2 (Nrf2) and c-Jun] to the antioxidant response element (ARE) on HO-1 and NQO1 promoters. Down-regulation of Nrf2 and/or c-Jun using dominant-negative mutants (DNMs) or siRNA diminished the expression of HO-1 and NQO1, suggesting that Nrf2 and c-Jun are key transcription factors modulating HO-1/NQO1 expression. Moreover, PI3 kinase and mitogen-activated protein kinase (MAPK) signaling pathways were shown to be involved in HO-1 and/or NQO1 expression by isoflavones. Our data collectively suggest that HO-1 and NQO1 play a critical role in antioxidant effects of isoflavone metabolites in rat brain astrocytes. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
DOI
10.1111/j.1471-4159.2011.07395.x
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE