Modulation of pro-survival Akt/Protein Kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability

J P E Spencer, C Rice-Evans, Robert J Williams

Research output: Contribution to journalArticle

288 Citations (Scopus)

Abstract

Much recent interest has focused on the potential of flavonoids to interact with intracellular signaling pathways such as with the mitogen-activated protein kinase cascade. We have investigated whether the observed strong neurotoxic potential of quercetin in primary cortical neurons may occur via specific and sensitive interactions within neuronal mitogen-activated protein kinase and Akt/protein kinase B (PKB) signaling cascades, both implicated in neuronal apoptosis. Quercetin induced potent inhibition of both Akt/PKB and ERK phosphorylation, resulting in reduced phosphorylation of BAD and a strong activation of caspase-3. High quercetin concentrations (30 μm) led to sustained loss of Akt phosphorylation and subsequent Akt cleavage by caspase-3, whereas at lower concentrations (
Original languageEnglish
Pages (from-to)34783-34793
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number37
DOIs
Publication statusPublished - 12 Sep 2003

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