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

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.

• Authors: Junsei Mimura, Kunio Kosaka, Atsushi Maruyama, Takumi Satoh, Nobuhiko Harada, Hidemi Yoshida, Kei Satoh, Masayuki Yamamoto, Ken Itoh
• Journal: Journal of biochemistry (J Biochem) Vol. 150 Issue 2 Pg. 209-17 (Aug 2011) ISSN: 1756-2651 [Electronic] England
• PMID: 21596795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Abietanes
• Intracellular Signaling Peptides and Proteins
• KEAP1 protein, human
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Plant Extracts
• RNA, Messenger
• Nerve Growth Factor
• HMOX1 protein, human
• Heme Oxygenase-1
• TXNRD1 protein, human
• Thioredoxin Reductase 1
• salvin

Topics

• Abietanes (pharmacology)
• Astrocytes (drug effects, metabolism)
• Cell Line, Tumor
• Gene Expression Regulation
• Glioblastoma (metabolism)
• Heme Oxygenase-1 (metabolism)
• Humans
• Intracellular Signaling Peptides and Proteins
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2 (genetics, metabolism)
• Nerve Growth Factor (genetics)
• Neurons (drug effects, metabolism)
• Plant Extracts (pharmacology)
• RNA, Messenger (biosynthesis)
• Thioredoxin Reductase 1 (metabolism)