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Title

Epicatechin induces NF-κB, 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

AuthorsGranado-Serrano, Ana B.; Martín, M. Ángeles ; Bravo, Laura ; Goya, Luis ; Ramos, Sonia ; Haegeman, Guy
KeywordsEpicatechin
NF-κB signalling
Activator protein-1
Nuclear factor-erythroid 2p45-related factor-2
Issue Date2010
PublisherCABI Publishing
CitationBritish Journal of Nutrition 103: 168-179 (2010)
AbstractThe 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-κB, 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 10m-epicatechin induced the NF-κB pathway in a time-dependent manner characterised by increased levels of IB kinase (IKK) and phosphorylated inhibitor of κB subunit-α(p-IB) and proteolytic degradation of IκB, which was consistent with an up-regulation of the NκF-B-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 NκF-B 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-κB 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. © 2009 The Authors.
Publisher version (URL)https://doi.org/10.1017/S0007114509991747
URIhttp://hdl.handle.net/10261/66665
Identifiersdoi: 10.1017/S0007114509991747
issn: 0007-1145
Appears in Collections:(IF) Artículos
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