• BMB Reports
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• v.54 no.7
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• pp.380-385
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• 2021

Proper targeting of the βPAK-interacting exchange factor (βPIX)/G protein-coupled receptor kinase-interacting target protein (GIT) complex into distinct cellular compartments is essential for its diverse functions including neurite extension and synaptogenesis. However, the mechanism for translocation of this complex is still unknown. In the present study, we reported that the conventional kinesin, called kinesin-1, can transport the βPIX/GIT complex. Additionally, βPIX bind to KIF5A, a neuronal isoform of kinesin-1 heavy chain, but not KIF1 and KIF3. Mapping analysis revealed that the tail of KIF5s and LZ domain of βPIX were the respective binding domains. Silencing KIF5A or the expression of a variety of mutant forms of KIF5A inhibited βPIX targeting the neurite tips in PC12 cells. Furthermore, truncated mutants of βPIX without LZ domain did not interact with KIF5A, and were unable to target the neurite tips in PC12 cells. These results defined kinesin-1 as a motor protein of βPIX, and may provide new insights into βPIX/GIT complex-dependent neuronal pathophysiology.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.200.2-201
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• 2003

The effect of 15-deoxy-PGJ$_2$ on the differentiation of embryonic midbrain cells into dopaminergic neuronal cells, and the relationship between cell differentiation with activation of PPAR-yand possible signal pathway were investigated, 15-Deoxy-PGJ$_2$ increased neurite extension, a typical characteristics of the differentiation of embryonic midbrain cells isolated from 12 day's rat embryos in a dose-dependent manner. (omitted)

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.27-35
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• 2012

Oroxylin A is a flavone isolated from a medicinal herb reported to be effective in reducing the inflammatory and oxidative stresses. It also modulates the production of brain derived neurotrophic factor (BDNF) in cortical neurons by the transactivation of cAMP response element-binding protein (CREB). As a neurotrophin, BDNF plays roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. Adenosine $A2_A$ receptor colocalized with BDNF in brain and the functional interaction between $A2_A$ receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that oroxylin A modulates BDNF production in cortical neuron through the regulation of $A2_A$ receptor system. As expected, CGS21680 ($A2_A$ receptor agonist) induced BDNF expression and release, however, an antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production. Oroxylin A activated the PI3K-Akt-GSK-$3{\beta}$ signaling pathway, which is inhibited by ZM241385 and the blockade of the signaling pathway abolished the increase in BDNF production. The physiological roles of oroxylin A-induced BDNF production were demonstrated by the increased neurite extension as well as synapse formation from neurons. Overall, oroxylin A might regulate BDNF production in cortical neuron through $A2_A$ receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.

• Journal of Life Science
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• v.16 no.2 s.75
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• pp.315-322
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• 2006

FS11052, a novel microbial metabolite from Streptomyces spp. was identified as a small molecular substance and shown inhibition activities for the release of neurotransmitter from rat hippocampal neuron and PC12 cells. FS11052 is an inhibitor of tritiated norepinephrine ($[^3H]-NE$) release in high $K^+$ buffer solution containing ionomycin, indicating that FS11052 inhibits neurotransmitter release after the influx of $Ca^{2+}$ ions. When examined the effect of FS11052 on glucuronidase release from guinea pig neutrophils, FS11052 inhibited glucuronidase release: when treated with $5{\mu}g/ml$ of FS11052, which was not induced cellular cytotoxicity. The fact that the glucuronidase release in neutrophil and norepinephrine release in neuron was inhibited suggests the similarity in the locations and the mechanisms of FS11052 action targets. When treated with $5{\mu}g/ml$ of FS11052, $[^3H]-NE$ release and neurite extension for both rat hippocampal neurons and PC12 cells were prevented. These observations of FS11052 functioning as an inhibitor of neurotransmitter release suggest that FS11052 has an important role in synaptic transmission in neuron.

• Microbiology and Biotechnology Letters
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• v.28 no.2
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• pp.97-104
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• 2000

Screening of Biologically Active Essential Oils from Ligusticum tenuissimum. Kim, Min-Hae, Young-Gil Kim, Jin-Ha Lee, Keo-Pyo Hong, Jung-Ki Hong, Young-Joon Kong, and Hyeon-Yong Lee*. Division of Food and Biotechnology, Kangwon National University, Chunchon 200-701, Korea, 1 Regional Crop Development Station, Kangwon Agricultural Research & Extension Services, Chunchon 200-150, Korea-The biological activities of the crude essential oils from Ligusticum tenuissimum and the control(phthalic anhydride) were compared. About 60% of the growth of MCF7, A549, and Rep3B cells were inhibited by adding 1.0 mg/ml of the crude essential oils and below 40% was observed by the control. Cytotoxicity on human normal lung cell(IMR90) was scored as 34.4% for the crude oil and 26.4% for control, respectively. It was found that the crude essential oils were more effective than the control in anti mutagenecity tested by both Rec-assay and CRG V79 cells. The growth of human T-cell(Jurkat) was enhanced up to 1.21 times by adding the crude essential oil compared with the control. 50% of a-glucosidase activity was inhibited by both the crude essential oil and the control. ACE activities were inhibited 80.1 % and 65.3% by adding 1.0 mg/ml of the crude oil and the control, respectively. The higher enhancement of glutathione-S-transferase activity was observed in the crude oil than those in the control: 301 % v.s 234% at 1.0 mg/ml of the treatment. Thrombolytic activity was measured as 42.9% and 28.6% for the crude oil and the standard, respectively. The effect of the oil on the nerve cells PCI2, was observed as follows: the neurite of PCl2 cells was lengthened up to 255 /-lm longer than 205 /-lm of control. The number of neurite-bearing cells were about two times higher than control. The survival ratio of the crude essential oil was also increased up to 56.4% which was about two fold higher than in control.

• Biomedical Science Letters
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• v.3 no.1
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• pp.11-20
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• 1997

A regulation of differentiation in human neuroblastoma cells remains poorly understood, although it is of great importance in the clinical therapy of neuroblastoma. This study was aimed to elucidate effects of DNA synthesis inhibitors on the differentiation of neuroblastoma cells on the basis of morphological, biochemical and molecular respects. Three DNA synthesis inhibitors, sodium butyrate, hydroxyurea, cytosine arabinoside were used to explore their effects on the cellular morphology, the expression of c-myc and the elevation of choline acetyltransferase activity. They led to the extension or neurite-like processes reflecting differentiation or IMR-32 cells. In addition, the treatment of three DNA synthesis inhibitors resulted in the remarkable increases in the expression of c-myc as well as the stimulation of choline acetyltransferase activity which is involved in the synthesis of acetylcholine in the differentiated cholinergic neurons. Taken together, these results indicate that DNA synthesis inhibitors play an important role in the induction of cellular differentiation in IMR-32 cells. Furthermore these DNA synthesis inhibitors seem to be future useful to give an important clue (for the treatment of neuroblastoma).

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.5
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• pp.375-395
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• 2006

Purpose: Lingual nerve (LN) damage may be caused by either tumor resection or injury such as wisdom tooth extraction, Although autologous nerve graft is sometimes used to repair the damaged nerve, it has the disadvantage of necessity of another operation for nerve harvesting. Moreover, the results of nerve grafting is not satisfactory. The nerve growth factor (NGF) is well-known to play a critical role in peripheral nerve regeneration and its local delivery to the injured nerve has been continuously tried to enhance nerve regeneration. However, its application has limitations like repeated administration due to short half life of 30 minutes and an in vivo delivery model must allow for direct and local delivery. The aim of this study was to construct a well-functioning $rhNGF-{\beta}$ adenovirus for the ultimate development of improved method to promote peripheral nerve regeneration with enhanced and extended secretion of hNGF from the injured nerve by injecting $rhNGF-{\beta}$ gene directly into crush-injured LN in rat model. Materials and Methods: $hNGF-{\beta}$ gene was prepared from fetal brain cDNA library and cloned into E1/E3 deleted adenoviral vector which contains green fluorescence protein (GFP) gene as a reporter. After large scale production and purification of $rhNGF-{\beta}$ adenovirus, transfection efficiency and its expression at various cells (primary cultured Schwann cells, HEK293 cells, Schwann cell lines, NIH3T3 and CRH cells) were evaluated by fluorescent microscopy, RT-PCR, ELISA, immunocytochemistry. Furthermore, the function of rhNGF-beta, which was secreted from various cells infected with $rhNGF-{\beta}$ adenovirus, was evaluated using neuritogenesis of PC-12 cells. For in vivo evaluation of efficacy of $rhNGF-{\beta}$ adenovirus, the LNs of 8-week old rats were exposed and crush-injured with a small hemostat for 10 seconds. After the injury, $rhNGF-{\beta}$ adenovirus($2{\mu}l,\;1.5{\times}10^{11}pfu$) or saline was administered into the crushed site in the experimental (n=24) and the control group (n=24), respectively. Sham operation of another group of rats (n=9) was performed without administration of either saline or adenovirus. The taste recovery and the change of fungiform papilla were studied at 1, 2, 3 and 4 weeks. Each of the 6 animals was tested with different solutions (0.1M NaCl, 0.1M sucrose, 0.01M QHCl, or 0.01M HCl) by two-bottle test paradigm and the number of papilla was counted using SEM picture of tongue dorsum. LN was explored at the same interval as taste study and evaluated electro-physiologically (peak voltage and nerve conduction velocity) and histomorphometrically (axon count, myelin thickness). Results: The recombinant adenovirus vector carrying $rhNGF-{\beta}$ was constructed and confirmed by restriction endonuclease analysis and DNA sequence analysis. GFP expression was observed in 90% of $rhNGF-{\beta}$ adenovirus infected cells compared with uninfected cells. Total mRNA isolated from $rhNGF-{\beta}$ adenovirus infected cells showed strong RT-PCR band, however uninfected or LacZ recombinant adenovirus infected cells did not. NGF quantification by ELISA showed a maximal release of $18865.4{\pm}310.9pg/ml$ NGF at the 4th day and stably continued till 14 days by $rhNGF-{\beta}$ adenovirus infected Schwann cells. PC-12 cells exposed to media with $rhNGF-{\beta}$ adenovirus infected Schwann cell revealed at the same level of neurite-extension as the commercial NGF did. $rhNGF-{\beta}$ adenovirus injected experimental groups in comparison to the control group exhibited different taste preference ratio. Salty, sweet and sour taste preference ratio were significantly different after 2 weeks from the beginning of the experiment, which were similar to the sham group, but not to the control group.