• Molecules and Cells
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• v.45 no.8
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• pp.537-549
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• 2022

Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

• Journal of Nutrition and Health
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• v.37 no.7
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• pp.533-539
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• 2004

It has been reported that CLA decreases fat deposition in vivo and in vitro experiments. Among CLA isomers, c9t11 and t10c12 have been shown to exert active biological activities. For example, t10c12 reduces body weight and increases lean body mass, whereas, c9t11 has little effect on body fattness. However, the underlying molecular mechanism for the anti-obesity action of CLA isomers are not well understood. The purpose of this study was to examine the effects of t10c12 and c9t11 on lipid accumulation, cell proliferation, cell death and the expression levels of Ucp genes which are proposed as targets for anti-obesity in 3T3-L1 preadipocytes. Isomers of CLA at 50$\mu$M were added into preadipocyte differentiation medium for 3, 6 and 9days. Control cells received only the vehicle in the differentiation medium. Cytochemical analyses for lipid accumulation, cell proliferation and apotosis were carried out to compare lipidogenesis and cellular activity. RT-PCR analysis of GAPDH, Ucp 2,3 and 4 were also performed to find any modulatory effects of CLA isomers on the metabolic genes. Lipid accumulation indicated by Oil Red-O staining was inhibited in CLA isomers as compared to the control. T10c12 isomer showed less lipidogenesis than c9t11 did. A decrease occurred in CLA isomers as shown by BrdU incorporation. Apotosis has occured at higher level in t10c12 when compared to that of t9c11. Ucp 2, 3 and 4 genes were also upregulated in CLA isomers. T10c12 showed higher level of Ucp gene expressions than the c9t11 did. The biological activities of CLA isomers were also found to be different during differentiation of 3T3-L1 preadipocytes, suggesting that different isomers may be active in certain stage of lipidogenesis. The results indicate that both c9t11 and t10c12 CLA isomers decrease lipidogenesis, inhibit cell proliferation, increase cell death and upregulate in Ucp gene expressions during 3T3-L1 preadipocyte differentiation. T10c12 isomer was more effective than c9t11 in overall anti-obesity activity.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.149-158
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• 2000

The present study was attempted to examine the effect of staurosporine (STS) on secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal gland and to establish its mechanism of action. The perfusion of STS $(3{\times}10^{-7}{\sim}3{\times}10^{-8}\;M)$ into an adrenal vein for 20 min produced a dose-dependent inhibition in CA secretion evoked by ACh $(5.32{\times}10^{-3}\;M),$ high $K^+\;(5.6{\times}10^{-2}\;M),$ DMPP $(10^{-4}\;M\;for\;2\;min),$ McN-A-343 $(10^{-4}\;M\;for\;2\;min),$ cyclopiazonic acid $(10^{-5}\;M\;for\;4\;min)$ and Bay-K-8644 $(10^{-5}\;M\;for\;4\;min).$ Also, in the presence of tamoxifen $(2{\times}10^{-6}\;M),$ which is known to be a protein kinase inhibitor, CA secretory responses evoked by ACh, high $K^+,$ DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly depressed. However, in adrenal glands preloaded with STS $(10^{-7}\;M)$ under the presence of phorbol-12, 13-dibutyrate $(10^{-7}\;M),$ a specific activator of protein kinases (for 20 min), the inhibitory effect of STS on CA secretory responses evoked by ACh, high $K^+,$ DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid was greatly recovered to the extent of the control release as compared to those in the presence of STS only. These results demonstrate that STS causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization, indicating strongly that this effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells through preventing activation of protein kinases. Furthermore, these findings also suggest that these STS-sensitive protein kinases play a modulatory role partly in regulating the rat adrenomedullary CA secretion.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.71-78
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• 2001

Capsaicin, a pungent ingredient of hot pepper, elicits an intense burning pain when applied cutaneously and intradermally. Activation of capsaicin-gated channel in C-type dorsal root ganglion (DRG) neurons produces nonselective cationic currents. Although electrophysiological and biochemical properties of capsaicin-activated current $(I_{CAP})$ were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of $I_{CAP}$ by DAMGO $({\mu}-opioid\;agonist)$ and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of $I_{CAP}$ was significantly increased by DAMGO and completely reversed after washout, while $I_{CAP}$ was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on $I_{CAP}$. Mean action potential duration was significantly different between 'increased-by-DAMGO' group and 'decreased-by-DAMGO' group. Mean amplitudes of $I_H$ were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of $I_{CAP}$ (5/13). DAMGO also increased $I_{CAP}$ amplitude significantly in the same cells. The amplitude of $I_{CAP}$ was increased in additive manner by combined applications of DAMGO and CCK-8 in these cells. These results suggest that DAMGO and CCK-8 can either increase or decrease $I_{CAP}$ presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.

• Molecules and Cells
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• v.38 no.1
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• pp.1-13
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• 2015

Recent technical developments have transformed how neuroscientists can probe brain function. What was once thought to be difficult and perhaps impossible, stimulating a single set of long range inputs among many, is now relatively straight-forward using optogenetic approaches. This has provided an avalanche of data demonstrating causal roles for circuits in a variety of behaviors. However, despite the critical role that neuropeptide signaling plays in the regulation of behavior and physiology of the brain, there have been remarkably few studies demonstrating how peptide release is causally linked to behaviors. This is likely due to both the different time scale by which peptides act on and the modulatory nature of their actions. For example, while glutamate release can effectively transmit information between synapses in milliseconds, peptide release is potentially slower [See the excellent review by Van Den Pol on the time scales and mechanisms of release (van den Pol, 2012)] and it can only tune the existing signals via modulation. And while there have been some studies exploring mechanisms of release, it is still not as clearly known what is required for efficient peptide release. Furthermore, this analysis could be complicated by the fact that there are multiple peptides released, some of which may act in contrast. Despite these limitations, there are a number of groups making progress in this area. The goal of this review is to explore the role of peptide signaling in one specific structure, the bed nucleus of the stria terminalis, that has proven to be a fertile ground for peptide action.

• Journal of Acupuncture Research
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• v.21 no.4
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• pp.177-196
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• 2004

Objective : Rheumatoid arthritis is an autoimmune disease that pathogenesis is not fully understood and one of the most intractable musculoskeletal diseases. The concern in the immunopathogenesis of rheumatoid arthritis has been increased since 1980's and many immunotherapeutic agents including disease-modifying antirheumatic drugs (DMARDs) were developed and became the mainstay of treatment of rheumatoid arthritis. However, the cure of the disease has hardly been achieved. In oriental medicine, rheumatoid arthritis is related to Bi-Zheng(痺證), that presents pain, swelling, andlor loss of joint function as major clinical manifestations, and also known to be deeply involved in suppression of immune function related to weakness of Jung-Ki(正氣). The herbal medicine, empirically used, could be a potential resource of development of new immunotherapeutic agents for rheumatoid arthritis. Methods : We developed a search strategy using terms to include "rheumatoid arthritis and herbal medicine" combined with "Chinese medicine" and/or "Oriental medicine". The search was focused on experimental studies of herbal medicine (January 1999 to May 2004), which is known to have effects on immune function of patients with rheumatoid arthritis. Computerized search used Internet databases including KISS and RISS4U (Korea), CNKI (China), MOMJ (Main Oriental Medicine Journal, Japan), and PubMed. The articles were selected from journals of universities or major research institutes. Results : The literature search for experimental studies on effects of herbal medicine on immunity of rheumatoid arthritis retrieved a total of 21 articles (Korea; 8, China ; 12, Japan ; 1). Of 21 articles, 10 were related to single-drug formula, 2 to drug interaction, and 9 to multi-drug formula. Single-drug formula was mainly used for aqua-acupuncture and researches on active components. Studies of drug interaction emphasized harmony of Ki-Hyul(氣血) and balance of Han-Yeul(寒熱). Multi-drug regimen was mainly found among formulas for Bo-Ki-Hyul(補氣血) and Bo-Sin(補腎). Conclusion : Studies on rheumatoid arthritis were performed both in vitro and in vivo in vitro study, LPS-stimulated splenocytes and synoviocytes were treated with herbal medicine, resulting in proliferation and activation of immune cells and suppression of cytokine activities in vivo study CIA animal model demonstrated that herbal medicine decreased antibody production and improved function of immune cells. In cellular and molecular study herbal medicine showed profound effects on the level of mRNA expression of certain cytokines related to immune function. This study revealed that herbal medicine has significant immune modulatory action and could be used for recovery of immune dysfunction of rheumatoid arthritis patients.

• Korean Journal of Organic Agriculture
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• v.21 no.3
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• pp.423-435
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• 2013

The Codonopsis pilosula is traditional oriental herb associated with immune-modulatory functions and has anti-inflammatory properties and antioxidative activity. The present study was conducted to investigate the effects of dietary supplementation of Codonopsis pilosula extract powder (CEP) on the immunity and productivity in sows and piglets. A total of 20 pregnant sows were randomly assigned to two dietary treatments, which was given a corn-soybean meal diet with 0% and 0.5% CEP from 40 days prepartum to weaning (25 days postpartum). The immune system of piglets was expected to build up, because the feeding of CEP might increase the colostrum contents in sows. We also predicted that the growth performance of piglets also could be increased by some compensation effects due to the increased immunity of piglets. In results, immunities of sows and piglets as well as growth performance of piglets were not affected by the supplementation of CEP. The correlation between the colostrum and the serum on the IgG contents tended to have a positive correlation, although there was no significant (coefficient, 0.435; P=0.102). This result suggests that the supplementation of CEP may increase IgG contents in sows and piglets and contribute to improve immunity of piglets. In conclusion, it is thought that the physiologically active substances of CEP did not influence to the immune synergic effects in vivo of sows. Thus, the metabolic and action mechanism of the physiologically active substances of CEP should be explored to evaluate the availability of CEP as a feed additive for the immunomodulator.