Enhancement of Sodium Current in NG108-15 Cells during Neural Differentiation is Mainly due to an Increase in NaV1.7 Expression

Kawaguchi, Akinori; Asano, Hajime; Matsushima, Kayoko; Wada, Tetsuyuki; Yoshida, Shigeru; Ichida, Seiji

doi:10.1007/s11064-007-9334-9

Cited by 39 publications

(34 citation statements)

References 28 publications

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“…These channels not only play important roles in various physiological activities such as growth and metabolism in glial cells (19), but also in cell cycle regulation, proliferation, metastasis, invasion and apoptosis of astrocytoma cells (8,(19)(20)(21)(22)(23)(24)(25). VGSCs are mainly expressed in tumors of epithelial origin, and can participate in the biological behaviors of tumor cells, including direct spread, lateral movement, galvanotaxis, invasion and the secretory activity of the membrane (8,26,27).…”

Section: Discussionmentioning

confidence: 99%

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Xing

Wang

et al. 2014

Oncology Reports

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Abstract. In the present study, we designed and conducted a series of assays to determine the expression of voltage-gated sodium channel (VGSC) neonatal isoform Nav1.5 (nNav1.5) in human brain astrocytoma and its effect on the proliferation, migration, invasion and apoptosis of astrocytoma U251 cells. The results showed that nNav1.5 mRNA and protein were expressed in both human brain astrocytoma and normal brain tissues, but their expression levels in astrocytoma were significantly higher (P<0.05). In astrocytomas, nNav1.5 mRNA and protein levels were also different (P<0.05) and were correlated with pathological grades. The immunofluorescence confocal microscopy observations demonstrated that nNav1.5 protein was expressed in the nucleus, cytoplasm and membrane of the astrocytoma cells. After transfection, the small interfering RNA (siRNA) targeted to nNav1.5 significantly reduced the expression levels of SCN5A/nNav1.5 mRNA and protein by 57.2% (P<0.05) and 66.6% (P<0.05), respectively. The MTT, wound healing, Matrigel invasion and flow cytometric assays confirmed that following siRNA downregulation of the expression of the SCN5A/nNav1.5 gene, the in vitro proliferation and in vitro invasiveness of the U251 cells were significantly reduced (P<0.05 for both comparisons), and the apoptosis rate was significantly increased (P<0.05). These results revealed that nNav1.5 expression in human brain astrocytoma was upregulated, and its expression was positively correlated with the degree of malignancy. Additionally, reduced nNav1.5 expression significantly suppressed the proliferation and invasiveness of astrocytoma cells, indicating a new target in the molecular diagnosis and therapy of astrocytoma.

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Section: Discussionmentioning

confidence: 99%

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Xing

Wang

et al. 2014

Oncology Reports

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“…Among the nine isoforms (Na v 1.1 -Na v 1.9) of sodium channels, Na v 1.7 is localized at the axon growth cone (75,76); in addition, cell surface number of Na v 1.7 was up-regulated by neuronal differentiation (76,77). In the axon growth cone, gating of sodium channels increased both plasmalemmal expansion (71) and plasmalemmal insertion of sodium channels from the cytoplasm (72).…”

Section: Na V 17 and Axon Growth Conementioning

confidence: 99%

Lithium and Neuropsychiatric Therapeutics: Neuroplasticity via Glycogen Synthase Kinase-3β, β-Catenin, and Neurotrophin Cascades

Wada

2009

J Pharmacol Sci

125

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Abstract. Mood disorders are not merely attributed to the functional defect of neurotransmission, but also are due to the structural impairment of neuroplasticity. Chronic stress decreases neurotrophin levels, precipitating or exacerbating depression; conversely, antidepressants increase expression of various neurotrophins (e.g., brain-derived neurotrophic factor and vascular endothelial growth factor), thereby blocking or reversing structural and functional pathologies via promoting neurogenesis. Since the worldwide approval of lithium therapy in 1970, lithium has been used for its anti-manic, antidepressant, and anti-suicidal effects, yet the therapeutic mechanisms at the cellular level remain not-fully defined. During the last five years, multiple lines of evidence have shown that the mood stabilization and neurogenesis by lithium are due to the lithium-induced inhibition of glycogen synthase kinase-3β (GSK-3β), allowing accumulation of β-catenin and β-catenin-dependent gene transcriptional events. Altered levels of GSK-3β and β-catenin are associated with various neuropsychiatric and neurodegenerative diseases, while various classical neuropsychiatric drugs inhibit GSK-3β and up-regulate β-catenin expression. In addition, evidence has emerged that insulin-like growth factor-I enhances antidepression, antianxiety, memory, neurogenesis, and angiogenesis; antidepressants up-regulate expression of insulin-like growth factor-I, while insulin-like growth factor-I up-regulates brain-derived neurotrophic factor expression and its receptor TrkB level, as well as brain-derived neurotrophic factor-induced synaptic protein levels. More importantly, physical exercise and healthy diet raise transport of peripheral circulating insulin-like growth factor I into the brain, reinforcing the expression of neurotrophins (e.g., brain-derived neurotrophic factor) and the strength of cell survival signalings (e.g., phosphoinositide 3-kinase / Akt / GSK-3β pathway). This review will focus on the rapidly advancing new trends in the last five years about lithium, GSK-3β/ β-catenin, and neurotrophin cascades.

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“…In the context of our model system, the role of Brn-3a in sensory neuronal differentiation, the association between Brn-3a and AR is intriguing. As mentioned, Nav1.7 is the major voltage-gated sodium channel in sensory neurons and central to nociception (45), and its expression increases during the differentiation of neuroblastoma cell lines (47). In light of this, it is interesting to speculate on what effect the relative expression of Brn-3a and AR in peripheral neurons may have on the sensation of pain.…”

Section: Discussionmentioning

confidence: 96%

A Simple Technique for the Prediction of Interacting Proteins Reveals a Direct Brn-3a-Androgen Receptor Interaction

Berwick

Diss

Budhram-Mahadeo

et al. 2010

Journal of Biological Chemistry

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The formation of multiprotein complexes constitutes a key step in determining the function of any translated gene product. Thus, the elucidation of interacting partners for a protein of interest is of fundamental importance to cell biology. Here we describe a simple methodology for the prediction of novel interactors. We have applied this to the developmental transcription factor Brn-3a to predict and verify a novel interaction between Brn-3a and the androgen receptor (AR). We demonstrate that these transcription factors form complexes within the nucleus of ND7 neuroblastoma cells, while in vitro pull-down assays show direct association. As a functional consequence of the Brn3a-AR interaction, the factors bind cooperatively to multiple elements within the promoter of the voltage-gated sodium channel, Nav1.7, leading to a synergistic increase in its expression. Thus, these data define AR as a direct Brn-3a interactor and verify a simple interacting protein prediction methodology that is likely to be useful for many other proteins.Although the importance of protein-protein interaction is long established, the rise of postgenomic technologies, in particular interactomics in yeast (1), and the growing popularity of systems biology (2) have served to highlight the importance of protein complexes to cell biology. For example, in the field of transcriptional regulation, the discovery of cis-regulatory elements vast distances from the transcriptional start site of a gene requires the formation of protein complexes to bridge often huge expanses of genomic DNA (3). In addition, the concept of promoters and cis-regulatory elements as "coincidence detectors" that integrate and process a diversity of inputs into a decision on the expression of a gene requires the construction of complex molecular machinery to perform these tasks (4). Although the need to study multiprotein complexes in basic research is clear, its relevance to applied disciplines should not be underestimated. In the case of transcriptional complexes, there is a growing body of data supporting the idea that interactions between transcription factors and between transcription factors and co-factors constitute a potent target for therapeutic intervention (5-7). In addition to molecules that block or disrupt protein-protein interactions, the creation of drugs that stabilize a transcriptional complex has been postulated (6), thus suggesting the possibility that, by modulating protein binding events, genes critical to pathological processes may be switched on or off pharmacologically.The Brn-3a transcription factor (also known as Pou4F1) is a class IV POU (Pit-Oct-Unc) family transcription factor. It is expressed at high levels in the sensory neurons of the trigeminal ganglia and dorsal root ganglia (DRG) 2 and in specific structures of the brain (8). Brn-3a is indispensable for normal development because Brn-3a knock-out mice display a severe depletion of sensory neurons. Presumably grossly impaired in nociception and proprioception, these animals are unable to...

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Enhancement of Sodium Current in NG108-15 Cells during Neural Differentiation is Mainly due to an Increase in NaV1.7 Expression

Cited by 39 publications

References 28 publications

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Lithium and Neuropsychiatric Therapeutics: Neuroplasticity via Glycogen Synthase Kinase-3β, β-Catenin, and Neurotrophin Cascades

A Simple Technique for the Prediction of Interacting Proteins Reveals a Direct Brn-3a-Androgen Receptor Interaction

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