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dc.contributor.authorBahia, P.K.*
dc.contributor.authorRattray, Marcus*
dc.contributor.authorWilliams, R.J.*
dc.date.accessioned2016-09-21T09:33:21Z
dc.date.available2016-09-21T09:33:21Z
dc.date.issued2008-09
dc.identifier.citationBahia PK, Rattray M and Williams RJ (2008) Dietary flavonoid (-)epicatechin stimulates phosphatidylinositol 3-kinase-dependent anti-oxidant response element activity and up-regulates glutathione in cortical astrocytes. Journal of Neurochemistry. 106(5): 2194-2204.
dc.identifier.urihttp://hdl.handle.net/10454/9035
dc.descriptionNo
dc.description.abstractFlavonoids are plant-derived polyphenolic compounds with neuroprotective properties. Recent work suggests that, in addition to acting as hydrogen donors, they activate protective signalling pathways. The anti-oxidant response element (ARE) promotes the expression of protective proteins including those required for glutathione synthesis (xCT cystine antiporter, gamma-glutamylcysteine synthetase and glutathione synthase). The use of a luciferase reporter (ARE-luc) assay showed that the dietary flavan-3-ol (-)epicatechin activates this pathway in primary cortical astrocytes but not neurones. We also examined the distribution of NF-E2-related factor-2 (Nrf2), a key transcription factor in ARE-mediated gene expression. We found, using immunocytochemistry, that Nrf2 accumulated in the nuclei of astrocytes following exposure to tert-butylhydroquinone (100 microM) and (-)epicatechin (100 nM). (-)Epicatechin signalling via Nrf2 was inhibited by wortmannin implicating a phosphatidylinositol 3-kinase-dependent pathway. Finally, (-)epicatechin increased glutathione levels in astrocytes consistent with an up-regulation of ARE-mediated gene expression. Together, this suggests that flavonoids may be cytoprotective by increasing anti-oxidant gene expression.
dc.subjectAnimals
dc.subject; Antioxidants
dc.subject; Astrocytes
dc.subject; COS cells
dc.subject; Catechin
dc.subject; Cells
dc.subject; Cercopithecus aethiops
dc.subject; Cerebral cortex
dc.subject; Enzyme inhibitors
dc.subject; Flavonoids
dc.subject; Food
dc.subject; Gene expression regulation
dc.subject; Glutathione
dc.subject; Hydroquinones
dc.subject; Mice
dc.subject; NF-E2-related factor 2
dc.subject; Neuroprotective agents
dc.subject; Oxidative stress
dc.subject; Phosphatidylinositol 3-kinases
dc.subject; Response elements
dc.subject; Signal transduction
dc.subject; Up-regulation
dc.titleDietary flavonoid (-)epicatechin stimulates phosphatidylinositol 3-kinase-dependent anti-oxidant response element activity and up-regulates glutathione in cortical astrocytes
dc.status.refereedYes
dc.typeArticle
dc.type.versionNo full-text in the repository
dc.identifier.doihttps://doi.org/10.1111/j.1471-4159.2008.05542.x


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