Preferential expression of antioxidant response element mediated gene expression in astrocytes

Transcriptional control of target genes by antioxidant/electrophile respons e elements has been well described in peripheral tissues. Genes that are re gulated by this mechanism include the antioxidant enzymes NAD(P)H:quinone o xidoreductase, gamma -glutamyl cystine synthetase and glutathione-S-transfe rase. Antioxidant/electrophile response elements within a gene's promoter c onfer induction by low-molecular-weight electrophilic compounds such as ter t-butylhydroquinone and dimethyl fumarate. We have now examined the ability of antioxidant/electrophile response elements to elicit gene expression in neurons and astrocytes in both brain slices and primary cultures using tra nsient transfection of promoter reporter constructs. Our results using a he at-stable human placental alkaline phosphatase reporter indicate that antio xidant/electrophile response element mediated gene expression is largely re stricted to astrocyte cell populations. Placental alkaline phosphatase expr ession was significantly elevated in astrocytes treated with the antioxidan t/electrophile response element inducer dimethyl fumarate. Mutant construct s lacking a functional antioxidant/electrophile response element abolished all placental alkaline phosphatase expression in astrocytes. We suggest tha t astrocytic metabolic processes that normally aid and/or protect neurons m ay be controlled via this inducible system.