Preferential expression of antioxidant response element mediated gene expression in astrocytes

J Neurochem. 2001 Mar;76(6):1670-8. doi: 10.1046/j.1471-4159.2001.00157.x.


Transcriptional control of target genes by antioxidant/electrophile response elements has been well described in peripheral tissues. Genes that are regulated by this mechanism include the antioxidant enzymes NAD(P)H:quinone oxidoreductase, gamma-glutamyl cystine synthetase and glutathione-S-transferase. Antioxidant/electrophile response elements within a gene's promoter confer induction by low-molecular-weight electrophilic compounds such as tert-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 transient transfection of promoter reporter constructs. Our results using a heat-stable human placental alkaline phosphatase reporter indicate that antioxidant/electrophile response element mediated gene expression is largely restricted to astrocyte cell populations. Placental alkaline phosphatase expression was significantly elevated in astrocytes treated with the antioxidant/electrophile response element inducer dimethyl fumarate. Mutant constructs lacking a functional antioxidant/electrophile response element abolished all placental alkaline phosphatase expression in astrocytes. We suggest that astrocytic metabolic processes that normally aid and/or protect neurons may be controlled via this inducible system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Base Sequence
  • Biolistics
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology*
  • Dimethyl Fumarate
  • Fumarates / pharmacology
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Genes, Reporter
  • Glioma
  • Glutamate-Cysteine Ligase / genetics*
  • Glutathione Transferase / genetics*
  • Humans
  • Hybridomas
  • Hydroquinones / pharmacology
  • In Vitro Techniques
  • Molecular Sequence Data
  • Neuroblastoma
  • Neuroglia / cytology
  • Neuroglia / physiology
  • Promoter Regions, Genetic*
  • Quinone Reductases / genetics*
  • Rats
  • Recombinant Fusion Proteins / biosynthesis
  • Transfection


  • Antioxidants
  • Fumarates
  • Hydroquinones
  • Recombinant Fusion Proteins
  • 2-tert-butylhydroquinone
  • Quinone Reductases
  • Glutathione Transferase
  • Glutamate-Cysteine Ligase
  • Dimethyl Fumarate