Dexamethasone indirectly induces Ndrg2 expression in rat astrocytes

Kou Takahashi, Akiyoshi Saitoh, Misa Yamada, Takashi Iwai, Masatoshi Inagaki, Mitsuhiko Yamada

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

N-myc downstream-regulated gene 2 (Ndrg2) has been associated with cell proliferation, differentiation, and apoptosis. Ndrg2 expression in the brain is induced by glucocorticoid treatment or chronic stress in vivo. It has been postulated that glucocorticoid-induced Ndrg2 expression in astrocytes is regulated by the glucocorticoid response element half-site (GRE1/2) upstream of the Ndrg2 transcription site. Here we examined the mechanisms of dexamethasone-induced Ndrg2 expression in rat astrocytes. Ndrg2 mRNA expression in primary astrocytes was significantly increased after 24 hr of exposure to dexamethasone in a concentration-dependent manner. Dexamethasone-induced Ndrg2 mRNA and protein expression was blocked by pretreatment with RU486, a glucocorticoid receptor antagonist. Moreover, dexamethasone-induced Ndrg2 mRNA expression was reduced by pretreatment with the protein synthesis inhibitor cycloheximide. The Ndrg2 reporter assay showed that deletion of a putative GRE1/2, located upstream of Ndrg2, did not affect induction by dexamethasone. A region between -755 and -701 bp from the transcription start site was shown to regulate induction by dexamethasone using promoter constructs progressively deleted from the 5′ to 3′ ends. This region contained the predicted transcription factor binding sites for early B-cell factor 1 (Ebf1), nuclear factor-κB (NFκB), and paired box gene 5 (Pax5). Mutation at the NFκB- or Pax5-binding site, but not the Ebf1 binding site, abolished dexamethasone-induced promoter activation. These results indicate that Ndrg2 expression was indirectly induced by dexamethasone at the DNA level, potentially by the binding of NFκB or Pax5 to the transcription factor binding sites, and GRE1/2 was not involved in this induction.

Original languageEnglish
Pages (from-to)160-166
Number of pages7
JournalJournal of Neuroscience Research
Volume90
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

Keywords

  • Astroglia
  • Glucocorticoids
  • RU38486

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Takahashi, K., Saitoh, A., Yamada, M., Iwai, T., Inagaki, M., & Yamada, M. (2012). Dexamethasone indirectly induces Ndrg2 expression in rat astrocytes. Journal of Neuroscience Research, 90(1), 160-166. https://doi.org/10.1002/jnr.22727