Activation of Nrf2-regulated glutathione pathway genes by ischemic preconditioning

Karen F S Bell, Jill H Fowler, Bashayer Al-Mubarak, Karen Horsburgh, Giles E Hardingham

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Prophylactic pharmacological activation of astrocytic gene expression driven by the transcription factor Nrf2 boosts antioxidant defences and protects against neuronal loss in ischemia and other disease models. However, the role of Nrf2 in mediating endogenous neuroprotective responses is less clear. We recently showed that Nrf2 is activated by mild oxidative stress in both rodent and human astrocytes. Moreover, brief exposure to ischemic conditions was found to activate Nrf2 both in vivo and in vitro, and this was found to contribute to neuroprotective ischemic preconditioning. Here we show that transient ischemic conditions in vitro and in vivo cause an increase in the expression of Nrf2 target genes associated with the glutathione pathway, including those involved in glutathione biosynthesis and cystine uptake. Taken together, these studies indicate that astrocytic Nrf2 may represent an important mediator of endogenous neuroprotective preconditioning pathways.
Original languageEnglish
Pages (from-to)689524
JournalOxidative Medicine and Cellular Longevity
Publication statusPublished - 2011


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