PMID- 12564761 OWN - NLM STAT- MEDLINE DCOM- 20030402 LR - 20191106 IS - 0919-6544 (Print) IS - 0919-6544 (Linking) VI - 22 IP - 4 DP - 2002 Dec TI - The constitutive and inducible expression of Nurr1, a key regulator of dopaminergic neuronal differentiation, in human neural and non-neural cell lines. PG - 219-32 AB - 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 nonneural 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 mM dibutyryl cyclic AMP or 100 nm 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 alpha-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. FAU - Satoh, Jun-ichi AU - Satoh J AD - Department of Immunology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan. satoj@ncnp.go.jp FAU - Kuroda, Yasuo AU - Kuroda Y LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Australia TA - Neuropathology JT - Neuropathology : official journal of the Japanese Society of Neuropathology JID - 9606526 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA-Binding Proteins) RN - 0 (Enzyme Activators) RN - 0 (NR4A1 protein, human) RN - 0 (NR4A2 protein, human) RN - 0 (NR4A3 protein, human) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nr4a1 protein, mouse) RN - 0 (Nr4a2 protein, mouse) RN - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1) RN - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Steroid) RN - 0 (Receptors, Thyroid Hormone) RN - 0 (Transcription Factors) RN - 63X7MBT2LQ (Bucladesine) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Blotting, Northern MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Bucladesine/pharmacology MH - Cell Culture Techniques MH - Cell Differentiation/drug effects/genetics MH - DNA-Binding Proteins/*biosynthesis/drug effects MH - Enzyme Activators/pharmacology MH - *Gene Expression Regulation MH - Humans MH - Nerve Tissue Proteins/biosynthesis/drug effects MH - Neurons/cytology/drug effects/*physiology MH - Nuclear Receptor Subfamily 4, Group A, Member 1 MH - Nuclear Receptor Subfamily 4, Group A, Member 2 MH - RNA, Messenger/analysis MH - Receptors, Cytoplasmic and Nuclear MH - Receptors, Steroid MH - Receptors, Thyroid Hormone MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tetradecanoylphorbol Acetate/pharmacology MH - Transcription Factors/*biosynthesis/drug effects MH - Tumor Cells, Cultured EDAT- 2003/02/05 04:00 MHDA- 2003/04/04 05:00 CRDT- 2003/02/05 04:00 PHST- 2003/02/05 04:00 [pubmed] PHST- 2003/04/04 05:00 [medline] PHST- 2003/02/05 04:00 [entrez] AID - 10.1046/j.1440-1789.2002.00460.x [doi] PST - ppublish SO - Neuropathology. 2002 Dec;22(4):219-32. doi: 10.1046/j.1440-1789.2002.00460.x.