• Korean Journal of Acupuncture
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• v.28 no.2
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• pp.37-47
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• 2011

Objectives : We have studied the effects of GaAlAs (808 nm) low level laser therapy (LLLT) and acupuncture at BL40 on neuropathic pain in rats induced by lumbar spinal nerve 5 ligation. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, the lumbar spinal nerve 5 was ligated by 6-0 silk thread. After neuropathic surgery, we examined if the animals exhibited the behavioral sign of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, GaAlAs (808 nm) low level laser and acupuncture was inserted at BL40 once a day for 6 days. We examined the withdrawal response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-Fos, nociceptin and nociceptin receptor in the midbrain central gray of neuropathic rats. Results : The GaAlAs (808 nm) low level laser therapy and acupuncture at BL40 decreased the withdrawal response of mechanical allodynia that assessed with von Frey filament in LLLT group on 5 and 6 times and with acetone in AT group and LLLT on 6times. The LLLT and acupuncture at BL40 decreased the c-Fos protein expression in AT and LLLT groups. The 808 nm LLLT and acupuncture at BL40 decreased the nociceptin protein and nociceptin receptor protein in LLLT group. Conclusions : We have noticed that GaAlAs (808 nm) LLLT and acupuncture at BL40 decreased mechanical allodynia in the model of neuropathic pain. c-Fos, nociceptin and nociceptin receptor expression in the central gray of that group was also decreased. This study can be used as a basic resource on a study and a treatment of pain.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.3
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• pp.195-204
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• 2011

Introduction: This study examined the regulatory mechanism underlying the meal-induced changes in the hypothalamic-pituitary-adrenal gland (HPA) axis activity. Materials and Methods: Male Sprague-Dawley rats (250-300 g) were hired for two different experiments as follows; 1) rats received either 8% sucrose or 0.2% saccharin ad libitum after 48 h of food deprivation with the gastric fistula closed (real feeding) or opened (sham feeding). 2). rats received 5 ml of intra-oral infusion with 0.2% saccharin or distilled water after 48 h of food deprivation. One hour after food access, all rats were sacrificed by a transcardiac perfusion with 4% paraformaldehyde. The brains were processed for c-Fos immunohistochemistry and the cardiac blood was collected for the plasma corticosterone assay. Results: Real feedings with sucrose or saccharin and sham feeding saccharin but not sucrose, following food deprivation decreased the plasma corticosterone level. c-Fos expression in the nucleus tractus of solitarius (NTS) of the fasted rats was increased by the consumption of sucrose but not saccharin, regardless of the feeding method. On the other hand, the consumption of sucrose or saccharin with real feeding but not the sham, induced c-Fos expression in the paraventricular nucleus (PVN) of the fasted rats. The intra-oral infusion with saccharin or water decreased the plasma corticosterone level of the fasted rats. Intra-oral water infusion increased c-Fos expression in both the PVN and NTS, but saccharin only in the NTS in the fasted rats. Conclusion: Neither restoration of the fasting-induced elevation of plasma corticosterone nor the activation of neurons in the PVN and NTS after refeeding requires the palatability of food or the post-ingestive satiety and caloric load. In addition, neuronal activation in the hypothalamic PVN may not be an implication in the restoration of the fasting-induced elevation of the plasma corticosterone by oropharyngeal stimuli of palatable food.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.159-170
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• 2011

Objectives : We have studied to know analgesic effects of the combination of Aconitum Cilliare Tuber with honey in the models of peripheral neuropathic pain. Methods : Neuropathic pain model was made by ligating left 5th lumbar spinal nerve. After 3 days, combination of Aconitum Ciliare Tuber and honey extract was administrated each alternate day. Administration was divided three groups, that is NP-OA1(0.06 mg/ml), NP-OA2(0.24 mg/ml), and NO-OA3(0.96 mg/ml). After that, we examined the withdrawl response of neuropathic rats legs by von Frey filament and acetone stimulation. And also we examined c-Fos, glutamic oxaloacetic transaminase(GOT), glutamate-pyruvate transaminase(GPT) and change of weight. Results : Mechanical allodynia in NP-OA1 groups were significantly decreased compared with the control group. Cold allodynia in all experimental groups were no significant differences with the control group. c-Fos protein expression on the central grey, all experimental groups were lower than that of control groups. But, there were no statistically significant differences. Change of weight in all experimental groups were significantly increased compare with the control group. In blood serum GOT in NP-OA1, NP-OA2 groups were significantly decreased compare with the control group. In blood serum GPT in all experimental groups were no significant difference with the control group. Conclusions : We had noticed that the combination of Aconitum Ciliare Tuber and honey decreased mechanical allodynia in the model of neuropathic pain compared with the control group and it has not efficacy in elevation of GOT, GPT and weight loss etc., the element of which becomes damage to liver. This study can be proposed that Aconitum Ciliare with Honey may be applicable to neuropathic pain in clinic. But it is reliability not that cold allodynia and c-Fos expression have effectively to control pain. Therefore we have to follow up about that.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.427-434
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• 2015

Significant evidence supports the role of the vestibular system in the regulation of blood pressure during postural movements. In the present study, the role of the vestibulo-spino-adrenal (VSA) axis in the modulation of blood pressure via the vestibulosympathetic reflex was clarified by immunohistochemical and enzyme immunoassay methods in conscious rats with sinoaortic denervation. Expression of c-Fos protein in the intermediolateral cell column of the middle thoracic spinal regions and blood epinephrine levels were investigated, following microinjection of glutamate receptor agonists or antagonists into the medial vestibular nucleus (MVN) and/or sodium nitroprusside (SNP)-induced hypotension. Both microinjection of glutamate receptor agonists (NMDA and AMPA) into the MVN or rostral ventrolateral medullary nucleus (RVLM) and SNP-induced hypotension led to increased number of c-Fos positive neurons in the intermediolateral cell column of the middle thoracic spinal regions and increased blood epinephrine levels. Pretreatment with microinjection of glutamate receptor antagonists (MK-801 and CNQX) into the MVN or RVLM prevented the increased number of c-Fos positive neurons resulting from SNP-induced hypotension, and reversed the increased blood epinephrine levels. These results indicate that the VSA axis may be a key component of the pathway used by the vestibulosympathetic reflex to maintain blood pressure during postural movements.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.2
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• pp.1-15
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• 2010

Objectives : This study was performed to evaluate the effects of root of Cibotii rhizoma(CR) ethanol extract on the tissue and neuronal damage of the spinal cord injury(SCI). Methods : SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. CR was orally given once a day for 7 days after SCI. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue(LFS) histochemistry. HSP72(as neuronal damage marker), MAP2(as nerve fiber degeneration marker), c-Fos(immediate early gene), and Bax(pro-apoptotic molecule) expressions were examined using immuno-histochemistry. Individual immuno-positive cells expressing HSP72, MAP2, c-Fos and Bax were observed on the damaged level and the upper thoracic and lower lumbar spinal segments. Results : 1. CR reduced degeneration of nerve fibers and motor neuron shrinkage in the ventral horn of the lower lumbar spinal segment, but generally it did not seem to ameliorate the tissue injury following SCI. 2. CR reduced demyelination in the ventral and lateral funiculus of the lower lumbar spinal segment. 3. CR reduced HSP72 expression on the neurons in the peri-central canal gray matter adjacent to the damaged region. 4. CR strengthened MAP2 expression on the motor neurons in the ventral horn and on nerve fibers in the lateral funiculus of the lower lumbar spinal segment. 5. CR reduced c-Fos positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. 6. CR reduced Bax positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. Conclusions : These results suggest that CR plays an inhibitory role against secondary neuronal damage and nerve fiber degeneration. following SCI.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.04a
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• pp.113-130
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• 2003

1. We have established a model system to study sodium chloride, an environmental factor, induced gene regulations. 2. ${\alpha}$ENaC, cox-2, and c-fos genes are regulated by sodium chloride at mRNA level as well as at protein level. 3. Regulation of ${\alpha}$ENaC requires syntheses of new protein(s). 4. COX-2 may have a important role for homeostasis in hypertonic situation.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.691-697
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• 1997

The mechanisms underlying opiate tolerance and dependence are not fully understood. We used human neuroblastoma SH-SY5Y cells as a model system for studying effects of morphine tolerance and withdrawal on c-myc induction and cAMP levels. It has been reported that regulation of c-fos by acute and chronic morphine withdrawal is mediated through alterations in CREB transcription factor. In this study, we examined the effects of morphine tolerance on c-myc expression and cAMP concentrations. The activation of opiate receptors by an acute morphine administration resulted in an increase in c-myc mRNA and a decrease in cAMP concentrations in a dose-dependent manner $(5,\;10,\;15,\;and\;20\;{\mu}M)$. On the other hand, the chronic treatment of morphine $(10\;{\mu}M\;for\;six\;days)$ did not induce the elevated expression of c-myc mRNA. The c-myc expression was slightly inhibited in comparison with that of the acute morphine response. However, cAMP concentrations were increased with regard to morphine withdrawal response. These results suggest that the alterations in c-myc expression might imply a significant opiate regulation relating to morphine tolerance. This observation differs from increased expression of c-fos via regulation of cAMP pathway.

• Molecules and Cells
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• v.37 no.9
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• pp.685-690
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• 2014

Osteoclasts are large polykaryons that have the unique capacity to degrade bone and are generated by the differentiation of myeloid lineage progenitors. To identify the genes involved in osteoclast development, we performed microarray analysis, and we found that carboxypeptidase E (CPE), a prohormone processing enzyme, was highly upregulated in osteoclasts compared with their precursors, bone marrow-derived macrophages (BMMs). Here, we demonstrate a novel role for CPE in receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. The overexpression of CPE in BMMs increases the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts and the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are key regulators in osteoclastogenesis. Furthermore, employing CPE knockout mice, we show that CPE deficiency attenuates osteoclast formation. Together, our data suggest that CPE might be an important modulator of RANKL-induced osteoclast differentiation.

• YAKHAK HOEJI
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• v.41 no.5
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• pp.629-637
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• 1997

Tumor necrosis factor-${alpha}$ (TNF) induced a cytotoxic response in ME-180 cervical carcinoma cells in vitro. This cytotoxic response was accompanied by a temporal series of mitogenic stimuli : increased c-fos, c-jun and jun-B expression. Depletion of protein kinase C (PKC) by exposure of ME-180 cells to 100ng/ml phorbol myristate acetate (PMA) for 24hours almost completely abolished TNF-mediated increase in these signals, indicating that a PKC-dependent pathway is involved in TNF-mediated increases in the expression of c-fos, c-jun and jun-B. Characteristics of TNF receptors after exposure to 100ng/ml PMA or 24hours were not altered, suggesting that diminished induction of these oncogenes by TNF after PMA treatment is not due to any changes at the receptor level. To examine whether a PKC-dependent pathway is involved in TNF-mediated cytotoxicity in ME-180 cells, cytotoxicity was measured after depletion of PKC. No apparent changes in cytototoxicity after PKC depletion suggest that a PKC-dependent pathway is not involved in TNF-mediated cytotoxicity. Furthermore, results from cytotoxicity tests after exposure to staurosporine (PKC inhibitor) did not show any changes in the TNF-mediated cytotoxicity, confirming that a PKC-dependent pathway is not involved in this process. These data indicate that 1) TNF induces expression of c-fos, c-jun and jun-B oncogenes via a PKC-dependent pathway and 2) PKC-dependent expression of these three oncogenes by TNF may not be involved in TNF-mediated cytotoxicity in ME-180 cells.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.683-692
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• 2004

Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.