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Title:
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Epicatechin induces NF-kB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells
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Author:
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Granado-Serrano, Ana Belén; Martín, María Angeles; Haegeman, Guy; Goya, Luis; Bravo, Laura; Ramos, Sonia
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Notes:
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The dietary flavonoid epicatechin has been reported to exhibit a wide range of biological activities. The objective of the present study was to
investigate the time-dependent regulation by epicatechin on the activity of the main transcription factors (NF-kB, activator protein-1 (AP-1)
and nuclear transcription factor erythroid 2p45-related factor (Nrf2)) related to antioxidant defence and survival and proliferation pathways in
HepG2 cells. Treatment of cells with 10mM-epicatechin induced the NF-kB pathway in a time-dependent manner characterised by increased
levels of IkB kinase (IKK) and phosphorylated inhibitor of kB subunit-a (p-IkBa) and proteolytic degradation of IkB, which was
consistent with an up-regulation of the NF-kB-binding activity. Time-dependent activation of the AP-1 pathway, in concert with enhanced
c-Jun nuclear levels and induction of Nrf2 translocation and phosphorylation were also demonstrated. Additionally, epicatechin-induced NF-kB
and Nrf2 were connected to reactive oxygen species intracellular levels and to the activation of cell survival and proliferation pathways, being
phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) associated to Nrf2 modulation and ERK
to NF-kB induction. These data suggest that the epicatechin-induced survival effect occurs by the induction of redox-sensitive transcription factors
through a tight regulation of survival and proliferation pathways.
The present study was supported by the grants AGL2004-302, AGL2007-64042 and CSD2007-00063 from the Spanish Ministry of Science and Innovation (CICYT) and 200870 I198 (CSIC). A. B. G.-S. is a predoctoral fellow of the Spanish Ministry of Science and Education. |
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Subject(s):
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-Epicatechin
-NF-kB signalling
-Activator protein-1
-Nuclear factor-erythroid 2p45-related factor-2 |
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Rights:
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(c) Cambridge University Press, 2010
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Document type:
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Article
Article - Published version |
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Published by:
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Cambridge University Press
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