Nrf2 promotes neuronal cell differentiation

Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721, USA
Free Radical Biology and Medicine (Impact Factor: 5.74). 09/2009; 47(6):867-879. DOI: 10.1016/j.freeradbiomed.2009.06.029
Source: PubMed


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.

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Available from: Fei Zhao, Dec 18, 2014
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    • "It has been reported that the concentrations of vitamin A are lower in cholestatic patients even during early stages of the disease, and vitamin A supplementation was found to provide protection against hepatic damage in a BDL rat model induced by bile duct ligation [19–22]. Vitamin A has also been reported to play its protective role by inducing Nrf2 upregulation in neuronal cells [23]. However, whether vitamin A has similar effects on liver tissue is largely unknown. "
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    • "The factor regulate gene include GSH synthesis, glutathione reductase and peroxidase families, NAD(P)H: quinone oxidoreductase1 (NQO1) [13]. Recent studies have shown multi-regulating potentials in many steps of cell biology [15,16]. The anti-tumor effects of Nrf2 were found to be mediated by its regulatory roles during glioma cell differentiation and growth inhibition in vitro[17,18]. "
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    • "2° antibody only; between 102 to 104 on arbitrary logarithmic scale). MAP2 numbers in SH-SY5Y cells ranged from 10 to 20%, while flow cytometric immunoreactivity for TUJ1 and nestin was around 40% (Figure 3C) in accordance with immunocytochemical detection (see Figure 3B) and published results [28,29] and responded appropriately to differentiation stimuli (retinoic acid treatment of SH-SY5Y cells; Figure 3D). "
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