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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2010Author
Martín, María Angeles
Haegeman, Guy
Goya, Luis
Bravo, Laura
Ramos, Sonia
Suggested citation
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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Show full item recordAbstract
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.