Dietary flavonoid (-)epicatechin stimulates phosphatidylinositol 3-kinase-dependent anti-oxidant response element activity and up-regulates glutathione in cortical astrocytes
Bahia, P.K. Rattray, Marcus Williams, R.J.
Bahia, P.K.
Rattray, Marcus
Williams, R.J.
Publication Date
2008-09
End of Embargo
Supervisor
Keywords
Animals, Antioxidants, Astrocytes, COS cells, Catechin, Cells, Cercopithecus aethiops, Cerebral cortex, Enzyme inhibitors, Flavonoids, Food, Gene expression regulation, Glutathione, Hydroquinones, Mice, NF-E2-related factor 2, Neuroprotective agents, Oxidative stress, Phosphatidylinositol 3-kinases, Response elements, Signal transduction, Up-regulation
Rights
Peer-Reviewed
Yes
Open Access status
closedAccess
Accepted for publication
Institution
Department
Awarded
Embargo end date
Collections
Additional title
Abstract
Flavonoids 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.
Version
No full-text in the repository
Citation
Bahia 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.
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Article