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The constitutive and inducible expression of Nurr1, a key regulator of dopaminergic neuronal differentiation, in human neural and non‐neural cell lines
Author(s) -
Satoh Junichi,
Kuroda Yasuo
Publication year - 2002
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1046/j.1440-1789.2002.00460.x
Subject(s) - biology , neurotrophic factors , dopaminergic , orphan receptor , tyrosine hydroxylase , endocrinology , medicine , receptor , microbiology and biotechnology , neural development , transcription factor , dopamine , gene , biochemistry
Nur‐related factor 1 (Nurr1), nerve growth factor‐induced gene B (NGFI‐B) and neuron‐derived orphan receptor‐1 (NOR‐1) constitute the orphan nuclear receptor subfamily of transcription factors. Previous studies showed that midbrain dopaminergic neuronal precursor cells failed to differentiate in Nurr1‐deficient mice. To investigate a role of Nurr1 in human neuronal function, Nurr1 mRNA expression was studied in human neural cell lines by RT‐PCR and northern blot analysis. Nurr1, NGFI‐B and NOR‐1 mRNA were coexpressed in all human neural and non‐neural cell lines under the serum‐containing culture condition, except for SK‐N‐SH neuroblastoma, in which Nurr1 mRNA was undetectable. The levels of Nurr1, NGFI‐B and NOR‐1 mRNA were elevated markedly in NTera2 teratocarcinoma‐derived neurons (NTera2‐N), a model of differentiated human neurons, following a 1.5 or 3 h‐exposure to 1 m m dibutyryl cyclic AMP or 100 n m phorbol 12‐myristate 13‐acetate. NGFI‐B mRNA levels were also elevated in NTera2‐N cells by exposure to 100 ng/mL brain‐derived neurotrophic factor (BDNF). To identify Nurr1‐target genes, the mRNA expression of 27 genes potentially involved in dopaminergic neuronal differentiation and survival, including BDNF, glia‐derived neurotrophic factor, their receptors, tyrosine hydroxylase and α‐synuclein, were studied in HEK293 cells following overexpression of Nurr1. None of these genes examined, however, showed significant changes. These results indicate that Nurr1, NGFI‐B and NOR‐1 mRNA are expressed constitutively in various human neural and non‐neural cell lines under the serum‐containing culture condition, and their levels are up‐regulated in human neurons by activation of protein kinase A or protein kinase C pathway, although putative coactivators expressed in dopaminergic neuronal precursor cells might be required for efficient transcriptional activation of Nurr1‐target genes.