Nrf2 promotes neuronal cell differentiation

Fei Zhao, Tongde Wu, Alexandria Lau, Tao Jiang, Zheping Huang, Xiao Jun Wang, Weimin Chen, Pak Kin Wong, Donna Zhang

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The transcription factor Nrf2 has emerged as a master regulator of the endogenous antioxidant response, which is critical in defending cells against environmental insults and in maintaining intracellular redox balance. However, whether Nrf2 has any role in neuronal cell differentiation is largely unknown. In this report, we have examined the effects of Nrf2 on cell differentiation using a neuroblastoma cell line, SH-SY5Y. Retinoic acid (RA) and 12-O-tetradecanoylphorbol 13-acetate, two well-studied inducers of neuronal differentiation, are able to induce Nrf2 and its target gene NAD(P)H quinone oxidoreductase 1 in a dose- and time-dependent manner. RA-induced Nrf2 up-regulation is accompanied by neurite outgrowth and an induction of two neuronal differentiation markers, neurofilament-M and microtubule-associated protein 2. Overexpression of Nrf2 in SH-SY5Y cells promotes neuronal differentiation, whereas inhibition of endogenous Nrf2 expression inhibited neuronal differentiation. More remarkably, the positive role of Nrf2 in neuronal differentiation was verified ex vivo in primary neuron culture. Primary neurons isolated from Nrf2-null mice showed a retarded progress in differentiation, compared to those from wild-type mice. Collectively, our data demonstrate a novel role for Nrf2 in promoting neuronal cell differentiation, which will open new perspectives for therapeutic uses of Nrf2 activators in patients with neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)867-879
Number of pages13
JournalFree Radical Biology and Medicine
Volume47
Issue number6
DOIs
StatePublished - Sep 15 2009

Fingerprint

Tretinoin
Neurons
Cell Differentiation
Neurodegenerative diseases
Microtubule-Associated Proteins
Differentiation Antigens
NAD
Oxidoreductases
Acetates
Transcription Factors
Intermediate Filaments
Antioxidants
Genes
Cells
Therapeutic Uses
Tetradecanoylphorbol Acetate
Neuroblastoma
Neurodegenerative Diseases
Oxidation-Reduction
Up-Regulation

Keywords

  • Free radicals
  • Keap1
  • Neuronal differentiation
  • NQO1
  • Nrf2
  • Oxidative stress
  • SH-SY5Y

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Nrf2 promotes neuronal cell differentiation. / Zhao, Fei; Wu, Tongde; Lau, Alexandria; Jiang, Tao; Huang, Zheping; Wang, Xiao Jun; Chen, Weimin; Wong, Pak Kin; Zhang, Donna.

In: Free Radical Biology and Medicine, Vol. 47, No. 6, 15.09.2009, p. 867-879.

Research output: Contribution to journalArticle

Zhao, F, Wu, T, Lau, A, Jiang, T, Huang, Z, Wang, XJ, Chen, W, Wong, PK & Zhang, D 2009, 'Nrf2 promotes neuronal cell differentiation', Free Radical Biology and Medicine, vol. 47, no. 6, pp. 867-879. https://doi.org/10.1016/j.freeradbiomed.2009.06.029
Zhao F, Wu T, Lau A, Jiang T, Huang Z, Wang XJ et al. Nrf2 promotes neuronal cell differentiation. Free Radical Biology and Medicine. 2009 Sep 15;47(6):867-879. https://doi.org/10.1016/j.freeradbiomed.2009.06.029
Zhao, Fei ; Wu, Tongde ; Lau, Alexandria ; Jiang, Tao ; Huang, Zheping ; Wang, Xiao Jun ; Chen, Weimin ; Wong, Pak Kin ; Zhang, Donna. / Nrf2 promotes neuronal cell differentiation. In: Free Radical Biology and Medicine. 2009 ; Vol. 47, No. 6. pp. 867-879.
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