Coordinate regulation of NAD(P)H : Quinone oxidoreductase and glutathione-S-transferases in primary cultures of rat neurons and glia: Role of the antioxidant/electrophile responsive element

NAD(P)H:quinone oxidoreductase (QR) and glutathione-S-transferases (GSTs) a re among the enzymes believed to protect an organism against oxidative stre ss. To test if redox-cycling compounds regulate the expression of these enz ymes in cells of neural origin, primary cultures of rat cerebellar neurons and glia were treated with tert-butyulydroquinone (tBHQ) and hydroquinone ( HQ). Basal levels of endogenous QR and GST activity were significantly grea ter in glia than neurons; and QR, GSTP1, and A3 were increased in glial but not neuronal cultures by treatment with tBHQ and HQ. A possible role for p rotein kinase C (PKC) in the tBHQ-mediated increase in QR and GST was evalu ated by activating PKC with phorbol 12-myristate 13-acetate or inhibiting P KC with bisindolylmaleimide I. PKC was not involved in maintaining basal ex pression or mediating the increased expression of GST or QR by tBHQ. Transc riptional activation of QR and rGSTP1 by tBHQ could be mediated through a c ommon responsive element present in the 5'-flanking region of both genes, t he antioxidant/electrophile responsive element (ARE/EpRE). Transient transf ection of the glial cultures with rGSTP1- or rQR1-ARE/EpRE-luciferase repor ter constructs demonstrated that tBHQ transcriptionally activates the ARE/E pRE. Thus, the increased expression of genes regulated by the ARE/EpRE in c ells of the central nervous system may provide protection against oxidative stress. GLIA 25:131-142, 1999. (C) 1999 Wiley-Liss, Inc.