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

dc.contributor.authorGranado-Serrano, Ana Belén
dc.contributor.authorMartín, María Angeles
dc.contributor.authorHaegeman, Guy
dc.contributor.authorGoya, Luis
dc.contributor.authorBravo, Laura
dc.contributor.authorRamos, Sonia
dc.date.accessioned2018-10-16T09:16:32Z
dc.date.available2018-10-16T09:16:32Z
dc.date.issued2010
dc.description.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-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.ca_ES
dc.description.sponsorshipThe 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.ca_ES
dc.identifier.doihttps://doi.org/10.1017/S0007114509991747
dc.identifier.idgrec018373
dc.identifier.issn0007-1145
dc.identifier.urihttp://hdl.handle.net/10459.1/64884
dc.language.isoengca_ES
dc.publisherCambridge University Pressca_ES
dc.relationinfo:eu-repo/grantAgreement/MEC//AGL2004-302/ES/
dc.relationinfo:eu-repo/grantAgreement/MEC//AGL2007-64042/ES/EVALUACION IN VITRO E IN VIVO DEL POTENCIAL QUIMIOPREVENTIVO DE FLAVANOLES DE LA DIETA FRENTE AL DESARROLLO DE CANCER COLONICO/
dc.relationinfo:eu-repo/grantAgreement/MEC//CSD2007-00063/ES/Nuevos Ingredientes de Alimentos Funcionales para Mejorar la Salud/
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1017/S0007114509991747ca_ES
dc.relation.ispartofBritish Journal of Nutrition, 2010, vol. 103, p. 168–179ca_ES
dc.rights(c) Cambridge University Press, 2010ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.subjectEpicatechinca_ES
dc.subjectNF-kB signallingca_ES
dc.subjectActivator protein-1ca_ES
dc.subjectNuclear factor-erythroid 2p45-related factor-2ca_ES
dc.titleEpicatechin 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 cellsca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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