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Human Neural (human + neural)
Terms modified by Human Neural Selected AbstractsThe constitutive and inducible expression of Nurr1, a key regulator of dopaminergic neuronal differentiation, in human neural and non-neural cell linesNEUROPATHOLOGY, Issue 4 2002Jun-ichi Satoh 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 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 ,-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. [source] Cytokines and neurotrophic factors fail to affect Nogo-A mRNA expression in differentiated human neurones: implications for inflammation-related axonal regeneration in the central nervous systemNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2002J.-I. Satoh Nogo is a novel myelin-associated inhibitor of neurite outgrowth which regulates stable neuronal connections during axonal regeneration following injury in the adult mammalian central nervous system (CNS). Because cytokines and neurotrophic factors play a key role in inflammation-related axonal regeneration, we investigated: (i) the constitutive expression of Nogo and the Nogo receptor (NgR) mRNA in human neural cell lines; (ii) Nogo and NgR mRNA levels in the NTera2 human teratocarcinoma cell line during retinoic acid (RA)-induced neuronal differentiation; and (iii) their regulation in NTera2-derived differentiated neurones (NTera2-N) after exposure to a battery of cytokines and growth factors potentially produced by activated glial cells at post-traumatic inflammatory lesions in the CNS. By reverse transcriptase-polymerase chain reaction analysis, the constitutive expression of Nogo-A, the longest isoform of three distinct Nogo transcripts and NgR mRNA was identified in a wide variety of human neural and non-neural cell lines. By Northern blot analysis, the levels of Nogo-A mRNA were elevated markedly in NTera2 cells following RA-induced neuronal differentiation, accompanied by an increased expression of the neurite growth-associated protein GAP-43 mRNA. In contrast, Nogo-A, Nogo-B, NgR and GAP-43 mRNA levels were unaltered in NTera2-N cells by exposure to basic fibroblast growth factor, brain-derived neurotrophic factor, glia-derived neurotrophic factor, tumour necrosis factor-,, interleukin-1,, dibutyryl cyclic AMP or phorbol 12-myristate 13-acetate. These results indicate that both Nogo-A and NgR mRNA are coexpressed in various human cell types, including differentiated neurones, where their expression is unaffected by exposure to a panel of cytokines and neurotrophic factors which might be involved in inflammation-related axonal regeneration in the CNS. [source] |