Activation of Nrf2-Regulated Glutathione Pathway Genes by Ischemic Preconditioning

• Published in: Oxidative medicine and cellular longevity 2011-01, Vol.2011 (2011), p.1-7
• Main Authors: Bell, Karen F. S., Fowler, Jill H., al-Mubarak, Bashayer, Horsburgh, Karen, Hardingham, Giles E.
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Glutathione - metabolism; Ischemic Preconditioning; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Real-Time Polymerase Chain Reaction; Signal Transduction - physiology
• ISSN: 1942-0900; 1942-0994; 1942-0994
• DOI: 10.1155/2011/689524

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.