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Vafeiadou, Katerina, Vauzour, David 
ORCID: https://orcid.org/0000-0001-5952-8756, Rodriguez-Mateos, Ana, Whiteman, Matthew, Williams, Robert J. and Spencer, Jeremy P. E.
(2008)
Glial metabolism of quercetin reduces its neurotoxic potential.
Archives of Biochemistry and Biophysics, 478 (2).
pp. 195-200.
ISSN 0003-9861
Abstract
The neuroprotective effects of flavonoids will ultimately depend on their interaction with both neuronal and glial cells. In this study, we show that the potential neurotoxic effects of quercetin are modified by glial cell interactions. Specifically, quercetin is rapidly conjugated to glutathione within glial cells to yield 2'-glutathionyl-quercetin, which is exported from cells but has significantly reduced neurotoxicity. In addition, quercetin underwent intracellular O-methylation to yield 3'-O-methyl-quercetin and 4'-O-methyl-quercetin, although these were not exported from glia at the same rate as the glutathionyl adduct. The neurotoxic potential of both quercetin and 2'-glutathionyl-quercetin paralleled their ability to modulate the pro-survival Akt/PKB and extracellular signal-regulated kinase (ERK) signalling pathways. These data were supported by co-culture investigation, where the neurotoxic effects of quercetin were significantly reduced when they were cultured alongside glial cells. We propose that glial cells act to protect neurons against the neurotoxic effects of quercetin and that 2'-glutathionyl-quercetin represents a novel quercetin metabolite.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health |
| Depositing User: | David Vauzour |
| Date Deposited: | 29 Feb 2012 11:45 |
| Last Modified: | 19 Oct 2023 00:45 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/34820 |
| DOI: | 10.1016/j.abb.2008.07.014 |
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