Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 478, Issue 2, Pages 195-200Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2008.07.014
Keywords
flavonoid; quercetin; glutathione; neuron; neurotoxicity; glia; brain
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Funding
- Biotechnology and Biological Sciences Research Council [BB/C518222/1, BB/F008953/1]
- Medical Research Council [G0400278]
- Biotechnology and Biological Sciences Research Council [BB/C518222/1, BB/F008953/1] Funding Source: researchfish
- Medical Research Council [G0400278] Funding Source: researchfish
- BBSRC [BB/F008953/1] Funding Source: UKRI
- MRC [G0400278] Funding Source: UKRI
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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 addion, 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. (c) 2008 Elsevier Inc. All rights reserved.
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