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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2010
Author
Granado-Serrano, Ana Belén
Martín, María Angeles
Haegeman, Guy
Goya, Luis
Bravo, Laura
Ramos, Sonia
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Granado-Serrano, Ana Belén; Martín, María Angeles; Haegeman, Guy; Goya, Luis; Bravo, Laura; Ramos, Sonia; . (2010) . 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. British Journal of Nutrition, 2010, vol. 103, p. 168–179. https://doi.org/10.1017/S0007114509991747.
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Abstract
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.
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http://hdl.handle.net/10459.1/64884
DOI
https://doi.org/10.1017/S0007114509991747
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British Journal of Nutrition, 2010, vol. 103, p. 168–179
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