Cortical glia have higher basal Nrf2 expression and ARE promotor activity than neurons. A, Western blot of heterologously expressed Nrf2 (105 kDa) and Nrf2DN (28 kDa) in HEK293 cells. B, A comigrating 105 kDa band corresponding to Nrf2 is observed in enriched cortical glial, but not neuronal, cultures. Densitometric analysis reveals an ∼12-fold difference in Nrf2 protein (n = 3); *p < 0.05. C, Coexpression of Nrf2 cDNA with a hPAP-encoding reporter of ARE-mediated gene expression (rQR51) greatly increases neuronal hPAP expression. Reporter constructs carrying a mutation within the core ARE consensus sequence (rQR51Mut) were not inducible. Coexpression with Nrf2DN cDNA suppresses both neuronal and glial hPAP expression. *p < 0.05, neuron comparison to pEF (empty vector) control; #p< 0.05, glial comparison to pEF control. D, E,Representative hPAP-stained astrocyte-like cells with coexpression of pEF vector only. F, G, With Nrf2 overexpression cells of both neuronal and glial morphology show ARE-driven hPAP expression. Data from hPAP experiments represent the mean ± SEM number of cells counted from triplicate coverslips over four independent experiments.