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dc.contributor.authorVauzour, David
dc.contributor.authorVafeiadou, Katerina
dc.contributor.authorRice-Evans, Catherine
dc.contributor.authorWilliams, Robert J.
dc.contributor.authorSpencer, Jeremy P. E.
dc.identifier.citationVauzour , D , Vafeiadou , K , Rice-Evans , C , Williams , R J & Spencer , J P E 2007 , ' Activation of pro-survival Akt and ERK1/2 signalling pathways underlie the anti-apoptotic effects of flavanones in cortical neurons ' , Journal of Neurochemistry , vol. 103 , no. 4 , pp. 1355-67 .
dc.identifier.otherPURE: 2234320
dc.identifier.otherPURE UUID: 23f35c88-9fab-407c-8efe-2de376af9f15
dc.identifier.otherPubMed: 17961201
dc.identifier.otherScopus: 35448949428
dc.description.abstractThere is growing interest in the potential beneficial effects of flavonoids in the aging and diseased brain. We have investigated the potential of the flavanone hesperetin and two of its metabolites, hesperetin-7-O-beta-d-glucuronide and 5-nitro-hesperetin, to inhibit oxidative stress-induced neuronal apoptosis. Exposure of cortical neurons to hydrogen peroxide led to the activation of apoptosis signal-regulating kinase 1 via its de-phosphorylation at Ser963, the phosphorylation of c-jun N-terminal kinase and c-Jun (Ser73) and the activation of caspase 3 and caspase 9. Whilst hesperetin glucuronide failed to exert protection, both hesperetin and 5-nitro-hesperetin were effective at preventing neuronal apoptosis via a mechanism involving the activation/phosphorylation of both Akt/protein kinase B and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Protection against oxidative injury and the activation of Akt and ERK1/2 followed a bell-shaped response and was most apparent at 100 nmol/L concentrations. The activation of ERK1/2 and Akt by flavanones led to the inhibition of the pro-apoptotic proteins, apoptosis signal-regulating kinase 1, by phosphorylation at Ser83 and Bad, by phosphorylation at both Ser136 and Ser112 and to the inhibition of peroxide-induced caspase 9 and caspase 3 activation. Thus, flavanones may protect neurons against oxidative insults via the modulation of neuronal apoptotic machinery.en
dc.relation.ispartofJournal of Neurochemistry
dc.subjectCell Survival
dc.subjectCells, Cultured
dc.subjectCerebral Cortex
dc.subjectEnzyme Activation
dc.subjectMAP Kinase Signaling System
dc.subjectMitogen-Activated Protein Kinase 1
dc.subjectMitogen-Activated Protein Kinase 3
dc.subjectProto-Oncogene Proteins c-akt
dc.titleActivation of pro-survival Akt and ERK1/2 signalling pathways underlie the anti-apoptotic effects of flavanones in cortical neuronsen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionAgriculture, Food and Veterinary Sciences
dc.contributor.institutionFood Policy, Nutrition and Diet
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
rioxxterms.typeJournal Article/Review

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