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Activation of antioxidant/electrophile-responsive elements in IMR-32 human neuroblastoma cells.

Abstract
The present investigation demonstrates distinct patterns of activation for antioxidant/electrophile-responsive elements (ARE/EpREs) in cells of neuronal versus hepatic origin suggesting the possibility of cell-/tissue-specific signaling pathways and/or transcription factors required for ARE/EpRE activation. The ARE/EpRE is a cis-acting regulatory element found in 5'-flanking regions of numerous genes including NAD(P)H:quinone oxidoreductase (QR) and glutathione S-transferases. Insomuch as ARE/EpRE activation has been studied primarily in hepatoma cell lines there is little information on how these responsive elements and corresponding genes are regulated in brain. ARE/EpRE-reporter constructs were transiently transfected into IMR-32 human neuroblastoma cells. Activation of ARE/EpRE sequences by tert-butylhydroquinone (tBHQ), a redox-cycling compound, in IMR-32 cells (20- to 30-fold) is dramatically different from the minimal response seen in HepG2 human hepatoma cells (2- to 3-fold). beta-napthoflavone, an ARE/EpRE inducer in HepG2 cells, as well as the oxidants hydrogen peroxide and tert-butyl hydroperoxide did not induce the ARE/EpRE in IMR-32 cells. In addition, we show that the core sequence containing a complete 5' palindrome is necessary for maximal activation of the ARE/EpRE in IMR-32 cells. Mutations within this palindromic sequence decrease basal level expression and block induction by tBHQ but not phorbol 12-myristate 13-acetate. Furthermore, activation of the hQR-ARE/EpRE by tBHQ correlates with induction of endogenous QR activity in IMR-32 neuroblastoma cells (15-fold). Thus, elucidating the mechanism of ARE/EpRE activation in this human neuroblastoma cell line may identify unknown transcription factors or signal transduction cascades regulating ARE/EpRE-driven gene expression.
AuthorsJ D Moehlenkamp, J A Johnson
JournalArchives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 363 Issue 1 Pg. 98-106 (Mar 01 1999) ISSN: 0003-9861 [Print] United States
PMID10049503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 1999 Academic Press.
Chemical References
  • Antioxidants
  • Hydroquinones
  • Butylated Hydroxyanisole
  • 2-tert-butylhydroquinone
  • NAD(P)H Dehydrogenase (Quinone)
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
Topics
  • Antioxidants (metabolism)
  • Butylated Hydroxyanisole (pharmacology)
  • Dose-Response Relationship, Drug
  • Down-Regulation (drug effects, genetics)
  • Enzyme Induction (drug effects)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Genes, Reporter (drug effects)
  • Humans
  • Hydroquinones (pharmacology)
  • NAD(P)H Dehydrogenase (Quinone) (genetics, metabolism)
  • Neuroblastoma
  • Neurons (metabolism)
  • Protein Kinase C (metabolism)
  • Regulatory Sequences, Nucleic Acid (genetics)
  • Signal Transduction (physiology)
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Transcriptional Activation (drug effects)
  • Tumor Cells, Cultured

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