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

Reference:

Spencer, J. P. E., Rice-Evans, C. and Williams, R. J., 2003. 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. Journal of Biological Chemistry, 278 (37), pp. 34783-34793.

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Official URL:

http://dx.doi.org/10.1074/jbc.M305063200

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 (

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