• BMB Reports
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• v.28 no.4
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• pp.316-322
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• 1995

The GTPase activating protein (GAP) can function both as a negative regulator and an effector of $p21^{ras}$. Overexpression of GAP in NIH-3T3 cells has been shown to inhibit transformation by ms or src. To investigate the function of GAP in a differentiative system, we overexpressed this protein in the nerve growth factor (NGF)-responsive PC12 cell line. Two-fold overexpression of GAP caused a delay of several days in the onset of NGF- but not FGF-induced neuronal differentiation of PC12 cells. However, the NGF-induced activation or tyrosine phosphorylation of upstream (Trk, PLC-${\gamma}1$, SHC) and downstream (B-Raf and $p44^{mapk/erk1}$) components of $p21^{ras}$, signalling cascade was not altered by GAP overexpression. Therefore, the change of phenotype induced by GAP was probably not due to GAP functioning as a negative regulator of $p21^{ras}$. Rather, we found that NGF-induced tyrosine phosphorylation of SNT, a specific target of neurotrophin-induced tyrosine kinase activity, was inhibited by GAP overexpression. SNT is thought to function upstream or independent of $p21^{ras}$. Thus in PC12 cells, overexpressed GAP may control the rate of neuronal differentiation through a pathway involving SNT rather than the $p21^{ras}$ signalling pathway.

• Biomedical Science Letters
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• v.26 no.4
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• pp.310-318
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• 2020

The sciatic nerve is the largest nerve among the peripheral nerves, and the damage to the sciatic nerve is caused by mechanical and physical pressure. This is an important disease that consumes a lot of time and money in the treatment process. Among them, research on relieving nerve pain caused by damage to the peripheral sciatic nerve has been made efforts to prevent and treat this disease through various methods such as drugs, natural products, electrical stimulation, exercise therapy, and massage. Existing treatments are not very effective in neurological pain, and countermeasures are needed. Forsythia Fructus, used in this study, has been used as a therapeutic agent for infectious diseases and a pain reliever for cancer from the past, and in past studies, it has been known to properly control the inflammatory response. In this study, rengyolone, a physiologically active substance of Forsythiae Fructus, was administered to rats that caused chronic left nerve pain to verify the pain relief effect. As a result of the experiment, it was found that mechanical pain and cold stimulation pain were significantly reduced in the rengyolone-treated group compared to the non-administered group. In addition, it was found that nerve growth factor (NGF) mRNA expression was significantly reduced and Cyclin-dependent kinase 2 (Cdc2) expression was increased in the rengyolone administration group. This increase in NGF expression is thought to be related to rengyolone's anti-inflammatory regulatory mechanism. It is expected that the reduced NGF was directly involved in pain relief.

• Journal of Life Science
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• v.22 no.9
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• pp.1180-1186
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• 2012

The purpose of this study was to investigate the effect of exercise preconditioning (EPC) on nerve growth factor (NGF), synapsin I, and choline acetyltransferase (ChAT) in the hippocampus of rats subjected to social isolation (SI). We randomly assigned four groups of male Sprague-Dawley (SD) rats (n=32) to the following treatments: GC: group housing control; IC: isolation control; GE: group housing exercise; IE: isolation exercise (n=8 each group). The rats underwent EPC 5 days a week for 8 weeks, and the speed of the treadmill was gradually increased (grade $0^{\circ}C$). After EPC, they were immediately subjected to SI for 8 weeks. The results showed that the protein levels of NGF, synapsin I, and ChAT in the hippocampus were significantly decreased in the IC group (p<0.05) compared with the GC group. However, these protein levels were significantly higher in the IE group (p<0.05). These results show that EPC may buffer the decline of function in the hippocampus by ameliorating the reduction in NGF, synapsin I, and ChAT induced by SI.

• The Zoological Society Korea : Newsletter
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• v.17 no.2
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• pp.13-18
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• 2000

• Journal of Life Science
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• v.26 no.5
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• pp.509-518
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• 2016

Asparagus cochinchinensis is a medical plant that has long been used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although several studies have been conducted on the anti-neuroinflammatory effects of A. cochinchinensis, the correlation between these effects and nerve growth factor (NGF) has not yet been examined. In this study, we investigated the effects of an aqueous extract of A. cochinchinensis (AEAC) on the secretion and action mechanism of NGF in neuronal cells. The concentration of the NGF protein in the supernatant collected from cultured cells increased significantly in B35 cells treated with AEAC in comparison with the vehicle-treated group without any specific cytotoxicity. Furthermore, the mRNA expression of NGF showed a very similar pattern to its protein concentration. To examine the bioactivity of NGF secreted from B35 cells, undifferentiated PC12 cells were cultured in an AEAC-conditioned medium and neuritic outgrowth was observed. The dendrite length of PC12 cells in the AEAC-treated group was significantly higher than that in the vehicle-treated group. Moreover, the level of the downstream effectors p-TrkA and p-ERK of the high-affinity NGF receptor was significantly higher in the AEAC-treated group, while the expression of the downstream effectors of the low-affinity NGF receptor was significantly lower in the same group. These results suggest that AEAC may contribute to the regulation of NGF expression and secretion in neuronal cells; it is therefore an excellent candidate for further investigation as a therapeutic drug for neurodegenerative diseases.

• Applied Microscopy
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• v.44 no.1
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• pp.21-29
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• 2014

Retinal glial responses to hypertensive glaucomatous injury were spatiotemporally surveyed. Retinas as a whole or vertical sections were processed for anti-glial fibrillary acidic protein (GFAP), anti-Iba1, anti-nerve growth factor (NGF), and anti-tumor necrosis factor (TNF)-${\alpha}$ immunohistochemistry for confocal microscopic analyses. The optic nerve head of paired controls was processed for electron microscopy. GFAP positive astrocytes appeared in the nerve fiber layer in the glaucomatous and control retinas, changing from fine protoplasmic to stout fibrous parallel to glaucomatous duration. Iba1 positive microglia appeared in both retinas, and enormous reaction appeared at the latest glaucomatous. M$\ddot{u}$ller reaction detected by GFAP reactivity expanded from the end feet to whole profile following to duration in the glaucomatous. NGF reactivity expended from the end feet to the proximal radial processes of the M$\ddot{u}$ller cells in both retinas according to glaucomatous duration. TNF-${\alpha}$ immunoreactivity in the nerve fiber layer was stronger in both the glaucomatous and controls than in the normal, and exceptionally at the latest glaucomatous was even lower than the normal. The astrocytes in the optic nerve head are interconnected with each other via gap junction. These results demonstrate that astrocyte reaction propagates to the contralateral via physical links, and TNF-${\alpha}$ is correlated with NGF production for neuroprotection in response to hypertensive glaucomatous injury.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.125-142
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• 2011

Objectives : Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficits. The purpose of this study was to evaluate the effects of Haein-tang(Hairen-tang) extract on functional recovery and pain release in the sciatic nerve after crushed sciatic nerve injury in rats. Methods : 1. Sciatic functional index(SFI) were performed on functional recovery. 2. c-Fos immunohistochemistry were performed on c-Fos expressions in the paraventricular nucleus(PVN) and ventrolateral periaqueductal gray(vIPAG). 3. Neurofilament immunohistochemistry were performed on neurofilament regeneration. 4. Western blot were performed on brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF) expression. Results : 1. Haein-tang(Hairen-tang) extract significantly enhanced the SFI value in the sciatic nerve injury and 100 mg/kg, 200 mg/kg Haein-tang(Hairen-tang)-treated group. 2. Haein-tang(Hairen-tang) extract significantly suppressed the sciatic nerve injury-induced increment of c-Fos expressions in the PVN and vIPAG in the sciatic nerve injury and 100 mg/kg, 200 mg/kg Haein-tang(Hairen-tang)-treated group. 3. Haein-tang(Hairen-tang) extract significantly increased neurofilament expression in the sciatic nerve injury and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang(Hairen-tang)-treated group. 4. Haein-tang(Hairen-tang) extract significantly controled the sciatic nerve injury-induced increment of BDNF and NGF expressions in the sciatic nerve injury and 100 mg/kg, 200 mg/kg Haein-tang(Hairen-tang)-treated group. Conclusions : These results suggest that Haein-tang(Hairen-tang) treatment after sciatic nerve injury is effective for the functional recovery by enhancing of axonal regeneration and suppressing of pain.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.328.3-329
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• 2002

A convenient bioassay of nerve growth factor(NGF) is essential for assessing its potency during the course of product development and quality controls afterwards. We have set up a cell-based bioassay for determining the potency of recombinant NGF using rat pheochromocytoma (PC12) cells. Cell survival was measured by monitoring the reduction of the alamarBlue$^{TM}$ dye by living cells. (omitted)d)

• Journal of Oral Medicine and Pain
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• v.34 no.4
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• pp.387-395
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• 2009

Nerve growth factor (NGF) and sensory neuropeptides are involved in the process of nociception at peripheral nerve fibers and wide spread in central nervous system. The aims of this study were to investigate NGF and sensory neuropeptides (substance P [SP] and calcitonin gene-related peptide [CGRP]) levels in human plasma and saliva, and the associations between these sensory neuropeptides levels and chronic orofacial pain symptoms. NGF, SP, and CGRP levels in plasma and resting whole saliva samples collected from 67 orofacial pain patients (joint pain, dental or periodontal pain, mucosal pain) and 36 pain free control subjects were measured by enzyme immunoassay. The characteristic pain intensity of each subject was measured using the Graded Chronic Pain Scale and the flow rate of resting whole saliva was measured. Joint pain patients group showed significantly higher plasma NGF level compared to each of dental pain patients (p<0.01), mucosal pain patients (p<0.01), and control group (p<0.01). Plasma NGF level of dental pain patients group was significantly higher than that of control group (p<0.01). Saliva SP level of dental pain patients group (p<0.05) and saliva CGRP level of mucosal pain group (p<0.05) were significantly higher than that of control group. Plasma and saliva SP levels of joint pain patients was significantly associated with pain intensity (plasma: standardized coefficient=0.599, p<0.01, saliva: standardized coefficient=0.504, p=0.05). In dental pain patients group, plasma SP (standardized coefficient=0.559, p<0.01), saliva SP (standardized coefficient=0.520, p<0.01) and saliva CGRP (standardized coefficient=0.599, p<0.01) levels were significantly associated with age. In mucosal pain patients group, plasma SP (standardized coefficient=0.495, p<0.05), saliva SP (standardized coefficient=0.500, p<0.05), and saliva CGRP (standardized coefficient=0.717, p<0.01) levels were significantly associated with age. NGF and neuropeptides may play a role in the maintenance of various orofacial pain symptoms. The examination of those levels in plasma and saliva helps understanding the mechanism of orofacial pain, and furthermore, can be applied to the diagnosis and therapy of orofacial pain.

• Proceedings of the KSME Conference
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• 2008.11a
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• pp.1585-1587
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• 2008

Fibroblast is constantly subjected to mechanical loads in connective tissues where mechanical signals are converted to intercellular biochemical events. The aim of this study is to understand the effects of tensile stress on the neurotrophin (NT) and transforming growth factor (TGF) expression of fibroblast in vitro. Nerve growth factor (NGF) stimulates fibroblast migration, and TGF is related to tissue repair. In this study, at the uniaxial stretch of 10% strain and frequency of 0.5 Hz, different resting times of 0, 20, and 60 min are placed in between 10 min stimulations periods. Results show increase in NGF mRNA levels and a substantial decrease in NT3 mRNA after 1 hr of stimulation, indicating that the tensile stress may regulate NGF and NT3, key factors for the neurocosmetic applications. The mRNA level for TGF-${\alpha}$ and TGF-${\beta}2$ had increased up to two-folds after 1 hr of stimulation, showing that the tensile stress may control TGF, an important part of wound healing.