Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes

Junsei Mimura, Kunio Kosaka, Atsushi Maruyama, Takumi Satoh, Nobuhiko Harada, Hidemi Yoshida, Kei Satoh, Masayuki Yamamoto, Ken Itoh

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Nerve growth factor (NGF) is a neurotrophic factor that plays an important role in neuronal cell development and survival. Carnosic acid (CA), a hydrophobic constituent of the herb rosemary, induces NGF production in human T98G glioblastoma cells, but the mechanism through which it works remains unknown. In the present study, we found a redox-sensitive transcription factor, Nrf2, which coordinates the expression of cytoprotective phase 2 genes, also participates in CA-inducible NGF expression. In T98G cells, CA caused NGF gene induction in a dose- and time-dependent manner without altering NGF mRNA stability. Simultaneously, CA increased Nrf2 nuclear accumulation and activated expression of prototypical Nrf2 target genes such as haem oxygenase 1 (HO-1) and thioredoxin reductase 1 (TXNRD1). Knockdown of endogenous Nrf2 by Nrf2-specific siRNA significantly reduced constitutive and CA-inducible NGF gene expression. In addition, NGF gene expression was enhanced by knockdown of Keap1, an Nrf2 inhibitor, in the absence of CA. Furthermore, CA induced NGF expression in normal human astrocytes in an Nrf2-dependent manner. These results highlight a role of Nrf2 in NGF gene expression in astroglial cells.

Original languageEnglish
Pages (from-to)209-217
Number of pages9
JournalJournal of biochemistry
Volume150
Issue number2
DOIs
Publication statusPublished - 2011 Aug

Keywords

  • NGF
  • Nrf2
  • astrocyte
  • carnosic acid
  • oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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