• Journal of Life Science
• /
• v.20 no.10
• /
• pp.1451-1457
• /
• 2010

Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of cell-cell signaling in neuronal systems. The serotonin transporter (SERT) on the plasma membrane controls the extracellular 5-HT level by reuptake of released 5-HT from the synaptic cleft, but the underlying regulation mechanism is unclear. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the carboxyl (C)-terminal region of SERT and found a specific interaction with protein kinase C-$\varepsilon$ (PKC-$\varepsilon$), a PKC isotype that is characterized as a calcium-independent and phorbol ester/diacylglycerol-sensitive serine/threonine kinase. PKC-$\varepsilon$ bound to the tail region of SERT but not to other members of the $Na^+/Cl^-$ dependent SLC6 gene family in the yeast two-hybrid assay. The C-terminal region of PKC-$\varepsilon$ is essential for interaction with SERT. In addition, these proteins showed specific interactions in the glutathione S-transferase (GST) pull-down assay. PKC-$\varepsilon$ phosphorylated the peptide of the SERT amino (N)-terminus in vitro. These results suggest that the phosphorylation of SERT by PKC-$\varepsilon$ may regulate SERT activity in plasma membrane.

• Journal of Neurogastroenterology and Motility
• /
• v.24 no.4
• /
• pp.656-668
• /
• 2018

Background/Aims MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. Methods We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. Results The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. Conclusions This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

• Journal of the Institute of Electronics Engineers of Korea SD
• /
• v.39 no.3
• /
• pp.61-72
• /
• 2002

In this paper, we propose two timing-driven routing algorithms for single-source net and multi-source net as applications of 1-Steiner heuristic algorithm. Using the method of substituting the cost of 1-Steiner heuristic algorithms with interconnection delay, our routing algorithms can route both single-source net and multi-source net which have all critical source-terminal pairs or one critical pair efficiently Our single-source net routing algorithm reduced the average maximum interconnection delay by up to 2.1% as compared with previous single-source routing algorithm, SERT, and 10.6% as compared with SERT-C. and Our multi-source net routing algorithm increased the average maximum interconnection delay by up to 2.7% as compared with MCMD A-tree, but outperforms it by up to average 1.4% when the signal net has only subset of critical node pairs.

• Korean Journal of Biological Psychiatry
• /
• v.25 no.1
• /
• pp.16-20
• /
• 2018

Objectives Psychological resilience is the ability to cope with stress. The genetic background behind psychological resilience is not much known. The serotonin transporter and dopamine transporter are implicated in stress related psychology and emotional processing. The aim of this study is to investigate a possible genetic role of functional polymorphisms of serotonin and dopamine transporters for psychological resilience. Methods A total of 951 healthy adult subjects were included. Psychological resilience was measured using Connor-Davidson Resilience Scale (CD-RISC). Genotyping was performed for serotonin transporter gene(SERT) promoter variable number tandem repeat (VNTR) and dopamine transporter gene(DAT1) 3'-untranslated region (UTR) VNTR. Genetic association analysis was conducted between genotypes and the CD-RISC score. Results No genetic association was observed for SERT promoter VNTR or DAT1 3'-UTR VNTR with CD-RISC score. No genetic interaction between SERT promoter VNTR and DAT1 3'-UTR VNTR with CD-RISC score was detected. Conclusions Either serotonin or dopamine transporter did not seem to play a significant role for psychological resilience in this sample.

• Bulletin of the Korean Chemical Society
• /
• v.27 no.12
• /
• pp.1969-1975
• /
• 2006

3D-QSAR model that correlates the biological activities with the chemical structures of quipazine derivatives acting on the serotonine transporter (SERT) was developed by comparative molecular field analysis (CoMFA). Total 8 models were constructed and a more accurate model, using close 1 $\AA$ grid spacing and StDev*Coefficients weight value gave better results. The contour maps with the best model, the resulting cross-validated correlation ($q^2$ : 0.744), and non-cross-validated correlation ($r^2$ : 0.966) indicate the steric and electrostatic environment of inhibitors in the SERT binding pocket. This study can be used as a putative picture of the pharmacophore in the design of novel and potent inhibitors.

• BMB Reports
• /
• v.39 no.4
• /
• pp.383-393
• /
• 2006

Little is known concerning the mechanisms responsible for the transplacental transfer of thiamine. So, the aim of this work was to characterize the placental uptake of thiamine from the maternal circulation, by determining the characteristics of $^3H$-thiamine uptake by a human trophoblast cell line (BeWo). Uptake of $^3H$-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) $Na^+$-dependent and $Cl^-$-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine. We conclude that $^3H$-thiamine uptake by BeWo cells seems to occur through a process distinct from thiamine transporter-1 (hThTr-1) and thiamine transporter-2 (hThTr-2). Rather, it seems to involve hSERT. Moreover, chronic (48 h) exposure of cells to caffeine ($1\;{\mu}M$) stimulated and chronic exposure to xanthohumol and iso-xanthohumol (1 and $0.1\;{\mu}M$, respectively) inhibited $^3H$-thiamine uptake, these effects being not mediated through modulation of the expression levels of either hThTr-1 or hSERT mRNA.

• Fire Science and Engineering
• /
• v.23 no.4
• /
• pp.59-66
• /
• 2009

This research aims to conduct a pilot study for the in-fire performance of headed studs, commonly used in composite structures over the world. The robustness of the shear studs in fire appears to be a key element to govern the composite behaviour after a sudden local instability developed in structures such as trusses and cellular beams. In order to experimentally evaluate the residual strength of studs in fire, the standard push-out test was modified for a half of the original set-up to be equipped with a furnace. The adjustments allow the steel section to have a 3-sided exposure against fire. Under the Standard ISO fire, the modified push-out tests under loading were conducted to identify the failure mechanism of the studs in relation to temperature developments.

• Nuclear Medicine and Molecular Imaging
• /
• v.43 no.1
• /
• pp.10-18
• /
• 2009

Purpose: We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) on $^{123}I$-FP-CIT SPECT for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinson's disease (IPD). Materials and Methods: N-fluoropropyl-$2{\beta}$-carbomethoxy-$3{\beta}$-4-[$^{123}I$]-iodophenylnortropane SPECT ($^{123}I$-FP-CIT SPECT) was performed in 8 patients with MSA (mean age: $64.0{\pm}4.5yrs$, m:f=6:2), 13 with early IPD (mean age: $65.5{\pm}5.3yrs$, m:f=9:4), and 12 healthy controls (mean age: $63.3{\pm}5.7yrs$, m:f=8:4). Standard regions of interests (ROls) of striatum to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal specific binding for DAT and hypothalamic and midbrain specific binding for SERT were calculated using region/reference ratio based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. Results: DAT in the whole striatum and striatal subregions were significantly decreased in both patient groups with MSA and early IPD, compared with healthy control (p<0.05 in all). In early IPD, a significant increase in the uptake ratio in anterior and posterior putamen and a trend of increase in caudate to putamen ratio was observed. In MSA, the decrease of DAT was accompanied with no difference in the striatal uptake pattern compared with healthy controls. Regarding the brain regions where $^{123}I$-FP-CIT binding was predominant by SERT, MSA patients showed a decrease in the binding of $^{123}I$-FP-CIT in the pons compared with controls as well as early IPD patients (MSA: $0.22{\pm}0.1$ healthy controls: $0.33{\pm}0.19$, IPD: $0.29{\pm}0.19$), however, it did not reach the statistical significance. Conclusion: In this study, the differential patterns in the reduction of DAT in the striatum and the reduction of pontine $^{123}I$-FP-CIT binding predominant by SERT could be observed in MSA patients on $^{123}I$-FP-CIT SPECT. We suggest that the quantification of SERT as well as DAT using $^{123}I$-FP-CIT SPECT is helpful to differentiate parkinsonian disorders in early stage.

• Bulletin of the Korean Chemical Society
• /
• v.23 no.10
• /
• pp.1439-1444
• /
• 2002

6-Nitroquipazine has higher binding affinity for SERT than other selective serotonin reuptake inhibitors. We have prepared 6-nitroquipazine based rhenium complexes which would lead to the development of potential SPECT imaging agents with $^{99m}Tc$ for 5-HT transporter.

• Korean Architects
• /
• no.9 s.47
• /
• pp.20-25
• /
• 1972

-편집주- ㆍ이사진들(ARCHITECTURE WITHOUT ARCHITECTS)은 1964년 11월 9일부터 1965년 2월 7일까지 약 4개월간에 걸쳐서 미국의 현대미술관에서 전시된 작품들로서 이 전시회는 현대미술관의 국제부의 협찬하에서 건축가 B. Rudofsky가 연구, 제작, 편집, 전시 및 디자인까지 도맡아 완성한 것이며, ㆍ이 비형식적이라 할 수 있는 건축물의 전시를 함에 있어서는 죤ㆍ시몬ㆍ구겐하임재단과 포드재단의 재정적인 지원을 받아서 이 계획의 연구를 이룰 수 있었으며 또한 건축가 Walter Gropius, Pietro Belluschi, Jose' Luis Sert, Richard Neutra, Gio Ponti, Kenzo Tange 등의 열광적인 협조와 추천으로서 이들 작품의 전시가 가능했다고 한다. ㆍ본 자료를 제공해주신 조창한 선생님에게 감사를 드립니다.