Cocoa flavonoids up-regulate antioxidant enzyme activity via the ERK1/2 pathway to protect against oxidative stress-induced apoptosis in HepG2 cells

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dc.contributor.authorMaria Angeles Martin
dc.contributor.authorAna Belen Granado Serrano
dc.contributor.authorSonia Ramos
dc.contributor.authorMaria Izquierdo Pulido
dc.contributor.authorLaura Bravo
dc.contributor.authorLuis Goya
dc.date.accessioned2014-04-05T07:07:16Z
dc.date.available2014-04-05T07:07:16Z
dc.date.issued2010
dc.description.abstractOxidative stress is widely recognized as an important mediator of apoptosis in liver cells and plays a pivotal role in the pathogenesis of several diseases. Cocoa flavonoids have shown a powerful antioxidant activity providing protection against oxidation and helping prevent oxidative stress-related diseases. However, the molecular mechanisms responsible for this protection are not fully understood. Thus, in this study we investigated the protective effect of a cocoa polyphenolic extract (CPE) against tert-butyl hydroperoxide (t-BOOH)-induced apoptosis and the molecular mechanisms involved in this process. Incubation of HepG2 cells with t-BOOH induced apoptosis as evidenced by caspase-3 activation. This effect was accompanied by increased reactive oxygen species formation and by transient activation of the extracellular regulated kinases (ERKs) as well as sustained activation of the c-Jun N-terminal kinases (JNKs). On the contrary, pretreatment of HepG2 cells with CPE prevented apoptosis through the reduction of reactive oxygen species generation and the modulation of the apoptotic pathways activated by t-BOOH. CPE treatment also activated survival signaling proteins, such as protein kinase B (AKT) and ERKs, and increased the activities of two antioxidant enzymes, glutathione peroxidase (GPx) and glutathione reductase (GR). ERKs implication on GPx and GR induction and the protective effect of CPE against t-BOOH-induced oxidative stress and apoptosis were confirmed through experiments with selective inhibitors. These findings suggest that CPE is an effective inductor of GPx and GR activities via ERK activation and that this up-regulation seems to be required to attenuate t-BOOH-induced injury.en_US
dc.identifier.citationJournal of Nutritional Biochemistry 21 (2010) 196–205en_US
dc.identifier.urihttp://hdl.handle.net/123456789/254
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.subjectApoptosisen_US
dc.subjectROSen_US
dc.subjectSignaling pathwaysen_US
dc.subjectGlutathione peroxidaseen_US
dc.subjectGlutathione reductaseen_US
dc.subjectPolyphenolsen_US
dc.titleCocoa flavonoids up-regulate antioxidant enzyme activity via the ERK1/2 pathway to protect against oxidative stress-induced apoptosis in HepG2 cellsen_US
dc.typeArticleen_US

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