title: Nrf2 promotes neuronal cell differentiation.
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.
authors: Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721, USA.
authors: Fei
authors: F
authors: Zhao
authors: Tongde
authors: T
authors: Wu
authors: Alexandria
authors: A
authors: Lau
authors: Tao
authors: T
authors: Jiang
authors: Zheping
authors: Z
authors: Huang
authors: Xiao-Jun
authors: XJ
authors: Wang
authors: Weimin
authors: W
authors: Chen
authors: Pak Kin
authors: PK
authors: Wong
authors: Donna D
authors: DD
authors: Zhang
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010703:Phorbol Esters / Q000378:metabolism; D034741:RNA, Small Interfering; D015533:Transcriptional Activation; D014212:Tretinoin / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D008869:Microtubule-Associated Proteins; D051267:NF-E2-Related Factor 2; D016900:Neurofilament Proteins; D010703:Phorbol Esters; D034741:RNA, Small Interfering; C061195:neurofilament protein M; D014212:Tretinoin; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human