TY - JOUR
T1 - Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes
AU - Mimura, Junsei
AU - Kosaka, Kunio
AU - Maruyama, Atsushi
AU - Satoh, Takumi
AU - Harada, Nobuhiko
AU - Yoshida, Hidemi
AU - Satoh, Kei
AU - Yamamoto, Masayuki
AU - Itoh, Ken
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - NGF
KW - Nrf2
KW - astrocyte
KW - carnosic acid
KW - oxidative stress
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U2 - 10.1093/jb/mvr065
DO - 10.1093/jb/mvr065
M3 - Article
C2 - 21596795
AN - SCOPUS:79961064830
VL - 150
SP - 209
EP - 217
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 2
ER -