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Oxidative Medicine and Cellular Longevity
Volume 2011 (2011), Article ID 689524, 7 pages
Research Article

Activation of Nrf2-Regulated Glutathione Pathway Genes by Ischemic Preconditioning

1Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK
2Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh EH8 9JZ, UK

Received 22 March 2011; Accepted 29 April 2011

Academic Editor: Florian Lang

Copyright © 2011 Karen F. S. Bell et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.