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    Dietary flavonoid (-)epicatechin stimulates phosphatidylinositol 3-kinase-dependent anti-oxidant response element activity and up-regulates glutathione in cortical astrocytes

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    Publication date
    2008-09
    Author
    Bahia, P.K.
    Rattray, Marcus
    Williams, R.J.
    Keyword
    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
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    Peer-Reviewed
    Yes
    
    Metadata
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    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.
    URI
    http://hdl.handle.net/10454/9035
    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
    http://dx.doi.org/10.1111/j.1471-4159.2008.05542.x
    Type
    Article
    Collections
    Life Sciences Publications

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