• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.555-561
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• 2020

TWIK-related two-pore domain K⁺ channel-2 (TREK-2) has voltage-independent activity and shows additional activation by acidic intracellular pH (pH_i) via neutralizing the E³³² in the cytoplasmic C terminal (Ct). We reported opposite regulations of TREK-2 by phosphatidylinositol 4,5-bisphosphate (PIP₂) via the alkaline K³³⁰ and triple Arg residues (R^355-357); inhibition and activation, respectively. The G³³⁴ between them appeared critical because its mutation (G³³⁴A) endowed hTREK-2 with tonic activity, similar to the mutation of the inhibitory K³³⁰ (K³³⁰A). To further elucidate the role of putative bent conformation at G³³⁴, we compared the dual mutation forms, K³³⁰A/G³³⁴A and G³³⁴A/R^355-7A, showing higher and lower basal activity, respectively. The results suggested that the tonic activity of G³³⁴A owes to a dominant influence from R^355-7. Since there are additional triple Arg residues (R^377-9) distal to R^355-7, we also examined the triple mutant (G³³⁴A/R^355-7A/R^377-9A) that showed tonic inhibition same with G³³⁴A/R^355-7A. Despite the state of tonic inhibition, the activation by acidic pH_i was preserved in both G³³⁴A/R^355-7A and G³³⁴A/R^355-7A/R^377-9A, similar to the R^355-7A. Also, the inhibitory effect of ATP could be commonly demonstrated under the activation by acidic pH_i in R^355-7A, G³³⁴A/R^355-7A, and G³³⁴A/R^355-7A/R^377-9A. These results suggest that the putative bent conformation at G³³⁴ is important to set the tug-of-war between K³³⁰ and R^355-7 in the PIP₂-dependent regulation of TREK-2.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.743-752
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• 1998

The atrial acetylcholine-activated $K^+\;(K_{ACh})$ channel is gated by the pertussis toxin-sensitive inhibitory G $(G_K)$ protein. Earlier studies revealed that ATP alone can activate the $K_{ACh}$ channel via transphosphorylation mediated by nucleoside-diphosphate kinase (NDPK) in atrial cells of rabbit and guinea pig. This channel can be activated by various agonists and also modulated its function by phosphorylation. ATP-induced $K_{ACh}$ channel activation (AIKA) was maintained in the presence of the NDPK inhibitor, suggesting the existence of a mechanism other than NDPK-mediated process. Here we hypothesized the phosphorylation process as another mechanism underlying AIKA and was undertaken to examine what kinase is involved in atrial cells isolated from the rat heart. Single application of 1 mM ATP gradually increased the activity of $K_{ACh}$ channels and reached its maximum $40{\sim}50$ sec later following adding ATP. AIKA was not completely reduced but maintained by half even in the presence of NDPK inhibitor. Neither ADP nor a non-hydrolyzable ATP analogue, AMP-PNP can cause AIKA, while a non-specific phosphatase, alkaline phosphatase blocked completely AIKA. PKC antagonists such as sphingosine or tamoxifen, completely blocked AIKA, whereas PKC catalytic domain increased AIKA. Taken together, it is suggested that the PKC-mediated phosphorylation is partly involved in AIKA.

• The Korean Journal of Physiology and Pharmacology
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• 제8권6호
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• pp.313-317
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• 2004

The present study were designed to characterize the action mechanisms of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries precontracted with high $K^+$(70 mM). For this, we simultaneously measured both muscle tension and cytosolic free $Ca^{2+}$ concentration $([Ca^{2+}]_i)$, using fura-2, in endothelium-intact, rabbit carotid arterial strips. In the artery with endothelium, high $K^+$ increased both $[Ca^{2+}]_i$ and muscle tension whereas ACh $(10{\mu}M)$ significantly relaxed the muscle and increased $[Ca^{2+}]_i$. In the presence of $N^G$-nitro-L-arginine (L-NAME, 0.1 mM), ACh increased $[Ca^{2+}]_i$ without relaxing the muscle. In the artery without endothelium, high $K^+$ increased both $[Ca^{2+}]_i$ and muscle tension although ACh was ineffective. 4-DAMP (10 nM) or atropine $(0.1{\mu}M)$ abolished ACh-induced increase in $[Ca^{2+}]_i$ and relaxation. The increase of $[Ca^{2+}]_i$ and vasorelaxation by ACh was siginificantly reduced by either $3{\mu}M$ gadolinium, $10{\mu}M$ lanthanum, or by $10{\mu}M$ SKF 96365. These results suggest that in rabbit carotid artery, ACh-evoked relaxation of 70 mM $K^+$-induced contractions appears to be mediated by the release of NO. ACh-evoked vasorelaxation is mediated via the $M_3$ subtype, and activation of the $M_3$ subtype is suggested to stimulate nonselective cation channels, leading to increase of $[Ca^{2+}]_i$ in endothelial cells.

• Molecules and Cells
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• 제27권3호
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• pp.307-312
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• 2009

The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a $Ca^{2+}$-free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by $GDP-{\beta}-S$, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external $Ca^{2+}$ influx, phospholipase C activation, and $Ca^{2+}$ release from internal storage in a G protein-independent and protein kinase C-independent manner.

• Journal of Ginseng Research
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• 제40권1호
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• pp.55-61
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• 2016

Background: A number of neurological and neurodegenerative diseases share impaired cognition as a common symptom. Therefore, the development of clinically applicable therapies to enhance cognition has yielded significant interest. Previously, we have shown that activation of lysophosphatidic acid receptors (LPARs) via gintonin application potentiates synaptic transmission by the blockade of $K^+$ channels in the mature hippocampus. However, whether gintonin may exert any beneficial impact directly on cognition at the neural circuitry level and the behavioral level has not been investigated. Methods: In the current study, we took advantage of gintonin, a novel LPAR agonist, to investigate the effect of gintonin-mediated LPAR activation on cognitive performances. Hippocampus-dependent fear memory test, synaptic plasticity in the hippocampal brain slices, and quantitative analysis on synaptic plasticity-related proteins were used. Results: Daily oral administration of gintonin for 1 wk significantly improved fear memory retention in the contextual fear-conditioning test in mice.We also found that oral administration of gintonin for 1 wk increased the expression of learning and memory-related proteins such as phosphorylated cyclic adenosine monophosphate-response element binding (CREB) protein and brain-derived neurotrophic factor (BDNF). In addition, prolonged gintonin administration enhanced long-term potentiation in the hippocampus. Conclusion: Our observations suggest that the systemic gintonin administration could successfully improve contextual memory formation at the molecular and synaptic levels as well as the behavioral level. Therefore, oral administration of gintonin may serve as an effective noninvasive, nonsurgical method of enhancing cognitive functions.

• 한국의상디자인학회지
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• 제19권3호
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• pp.193-206
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• 2017

The Seongsu handmade shoes street consists of subsidiaries, leather shoe manufacturers, and shoe stores associated with the business as a domestic shoe business cluster. Since its development in the 1980s, the shoe industry has been a center of shoe manufacturing but since the 2000s, it has lacked a fully developed environment, a uniform distribution system, market-oriented brand, marketing and design, and also suffers from an aging workforce. Seoul officials and Seongsu-dong small business owners must overcome these difficulties through town enterprise development, brand creation and marketing co-promoting composition of the characterization and distance, but the situation is still insignificant. The purpose of this study is to determine the actual situation as targeted at small merchant handmade shoes Seongsu-dong Street, to determine the factors in the problem, and to propose substantial improvements for Seongsu handmade shoes street. This study was a survey of street sales outlets in Seongsu handmade shoes street in Seoul. The spatial extent of the study was to set up the scope by reference to the directions given through the Seongsu handmade shoes street site. To build infrastructure facilities and distribution systems for the betterment of handmade shoes Seongsu-dong street, it is important to gain a competitive edge through a specialized industry such as a marketing strategy to establish branding as a specialized company. Shoemakers should also seek their own activation measures in areas such as training professionals, universities and corporate projects for joint participation in the ongoing development of new content. To pioneer the domestic and international sales channels, it is important to broaden the sales infrastructure. These areas will ultimately enable a significant contribution to strengthening national competitiveness.

• The Korean Journal of Physiology and Pharmacology
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• 제10권2호
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• pp.71-77
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• 2006

The goal of this study was to analyze the effects of genistein, a widely used tyrosine kinase inhibitor, on cloned Shaw-type $K^+$ currents, Kv3.1 which were stably expressed in Chinese hamster ovary (CHO) cells, using the whole-cell configuration of patch-clamp techniques. In whole-cell recordings, genistein at external concentrations from 10 to $100{\mu}M$ accelerated the rate of inactivation of Kv3.1 currents, thereby concentration-dependently reducing the current at the end of depolarizing pulse with an $IC_{50}$ value of $15.71{\pm}0.67{\mu}M$ and a Hill coefficient of $3.28{\pm}0.35$ (n=5). The time constant of activation at a 300 ms depolarizing test pulses from -80 mV to +40 mV was $1.01{\pm}0.04$ ms and $0.90{\pm}0.05$ ms (n=9) under control conditions and in the presence of $20{\mu}M$ genistein, respectively, indicating that the activation kinetics was not significantly modified by genistein. Genistein $(20{\mu}M)$ slowed the deactivation of the tail current elicited upon repolarization to -40 mV, thus inducing a crossover phenomenon. These results suggest that drug unbinding is required before Kv3.1 channels can close. Genistein-induced block was voltage-dependent, increasing in the voltage range $(-20\'mV{\sim}0\'mV)$ for channel opening, suggesting an open channel interaction. Genistein $(20{\mu}M)$ produced use-dependent block of Kv3.1 at a stimulation frequency of 1 Hz. The voltage dependence of steady-state inactivation of Kv3.1 was not changed by $20{\mu}M$ genistein. Our results indicate that genistein blocks directly Kv3.1 currents in concentration-, voltage-, time-dependent manners and the action of genistein on Kv3.1 is independent of tyrosine kinase inhibition.

• 한국융합학회논문지
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• 제9권11호
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• pp.403-415
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• 2018

본 연구는 뷰티프로보노활동의 영향요인을 분석하고, 관련활동이 지속적으로 이루어지기 위한 방안을 모색하고자 하는데 목적을 두고 있다. 본 연구에서는 연구모형과 가설을 설정하고, 수도권지역 미용전공자 701명의 설문분석을 실시하여 주요 분석결과를 도출하였다. 첫째, 뷰티프로보노 참여동기는 뷰티기술 및 지식을 활용하기 위함이며, 주로 봉사동아리활동을 통하여 참여하는 것으로 밝혀졌다. 둘째, 뷰티프로보노 활동만족도는 기관의 홍보모집과 연관성이 높았다. 봉사주관기관의 신뢰도는 기관운영수준과 참여를 통한 만족도가 높을수록 신뢰하는 경향이 높았다. 셋째, 뷰티프로보노활동을 통한 만족도, 조직에 대한 신뢰도가 높을수록 활동에 대한 지속가능의지도 높은 것으로 나타났다. 뷰티프로보노 활성화방안은 다양한 홍보채널의 개발, 봉사자들에 대한 교육강화, 봉사주관기관의 투명경영 등을 제시하였다. 한편, 본 연구는 조사대상의 한정이라는 연구의 한계를 갖고 있어 향후 조사대상의 확대와 뷰티전공 대학생들을 대상으로 한 다양한 측면에서의 연구가 지속되기를 기대한다.

• 한국문헌정보학회지
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• 제56권2호
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• pp.157-177
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• 2022

본 연구는 「도서관법」 개정에 따라 2023년부터는 4월 12일을 도서관의 날로 정하고 그 날로부터 1주간을 도서관주간으로 하게 된 것과 관련해 1964년부터 진행되고 있는 도서관주간의 의의와 역사, 국내외 도서관주간 사례 등을 분석하고 향후 도서관주간 활성화 방안을 모색하였다. 국내외 사례 분석을 통해 도출된 시사점을 바탕으로 도서관주간의 효율성 있는 운영방식, 프로그램 구성의 변화, 홍보전략의 다각화 세 가지 관점을 중심으로 활성화 방안을 제시하였다. 도서관주간을 활성화하기 위해 온·오프라인 플랫폼 구축, 명예 홍보대사 활용 등 다양한 행사 운영방법 제시, 이색적인 기념행사, 전국 동시 캠페인, 아카이빙, 상시 홍보 채널 및 체계 구축 등을 제안하였다. 따라서 본 연구는 2023년 시행될 도서관의 날 및 도서관주간을 추진하고 활성화하는데 참고자료로 활용될 수 있을 것으로 보인다.

• IMMUNE NETWORK
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• 제23권3호
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• pp.23.1-23.17
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• 2023

Inflammation is a series of host defense processes in response to microbial infection and tissue injury. Inflammatory processes frequently cause extracellular acidification in the inflamed region through increased glycolysis and lactate secretion. Therefore, the immune cells infiltrating the inflamed region encounter an acidic microenvironment. Extracellular acidosis can modulate the innate immune response of macrophages; however, its role for inflammasome signaling still remains elusive. In the present study, we demonstrated that macrophages exposed to an acidic microenvironment exhibited enhanced caspase-1 processing and IL-1β secretion compared with those under physiological pH. Moreover, exposure to an acidic pH increased the ability of macrophages to assemble the NLR family pyrin domain containing 3 (NLRP3) inflammasome in response to an NLRP3 agonist. This acidosis-mediated augmentation of NLRP3 inflammasome activation occurred in bone marrow-derived macrophages but not in bone marrow-derived neutrophils. Notably, exposure to an acidic environment caused a reduction in the intracellular pH of macrophages but not neutrophils. Concordantly, macrophages, but not neutrophils, exhibited NLRP3 agonist-mediated translocation of chloride intracellular channel protein 1 (CLIC1) into their plasma membranes under an acidic microenvironment. Collectively, our results demonstrate that extracellular acidosis during inflammation can increase the sensitivity of NLRP3 inflammasome formation and activation in a CLIC1-dependent manner. Thus, CLIC1 may be a potential therapeutic target for NLRP3 inflammasome-mediated pathological conditions.