• Journal of Yeungnam Medical Science
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• 제36권1호
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• pp.26-35
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• 2019

Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

• Journal of Korean Neurosurgical Society
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• 제57권4호
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• pp.235-241
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• 2015

Objective : Magnetic resonance imaging (MRI) of chronic subdural hematoma (CSDH) detects various patterns, which can be attributed to many factors. The purpose of this study was to measure the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and highly specific protein [beta-trace protein (${\beta}TP$)] for cerebrospinal fluid (CSF) in CSDHs, and correlate the levels of these markers with the MRI findings. Methods : Thirty one patients, treated surgically for CSDH, were divided on the basis of MRI findings into hyperintense and non-hyperintense groups. The concentrations of IL-6, IL-8, and ${\beta}TP$ in the subdural fluid and serum were measured. The ${\beta}TP$ was considered to indicate an admixture of CSF to the subdural fluid if ${\beta}TP$ in the subdural fluid $({\beta}TP_{SF})/{\beta}TP$ in the serum $({\beta}TP_{SER})>2$. Results : The mean concentrations of IL-6 and IL-8 of the hyperintense group (n=17) of T1-WI MRI were $3975.1{\pm}1040.8pg/mL$ and $6873.2{\pm}6365.4pg/mL$, whereas them of the non-hyperintense group (n=14) were $2173.5{\pm}1042.1pg/mL$ and $2851.2{\pm}6267.5pg/mL$ (p<0.001 and p=0.004). The mean concentrations of ${\beta}TP_{SF}$ and the ratio of ${\beta}TP_{SF}/{\beta}TP_{SER}$ of the hyperintense group (n=13) of T2-WI MRI were $7.3{\pm}2.9mg/L$ and $12.6{\pm}5.4$, whereas them of the non-hyperintense group (n=18) were $4.3{\pm}2.3mg/L$ and $7.5{\pm}3.9$ (p=0.011 and p=0.011). Conclusion : The hyperintense group on T1-WI MRI of CSDHs exhibited higher concentrations of IL-6 and IL-8 than non-hyperintense group. And, the hyperintese group on T2-WI MRI exhibited higher concentrations of ${\beta}TP_{SF}$ and the ratio of ${\beta}TP_{SF}/{\beta}TP_{SER}$ than non-hyperintense group. These findings appear to be associated with rebleeding and CSF admixture in the CSDHs.

• 대한화학회지
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• 제47권5호
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• pp.439-446
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• 2003

Au와 Ag 콜로이드 단일막 표면위에 흡착된 4-biphenylcarboxylic acid(BPCA)의 유도체인 4''-cyano-BPCA(c-BPCA), 4''-mercapto-BPCA(m-BPCA), 그리고 4''-amino-BPCA(a-BPCA)가 어떠한 배향을 하는지 알아보기 위해 표면증강라만(SER)분광법을 이용하여 연구하였다. 체계적인 분석을 위해 benzoic acid, biphenyl, 그리고 BPCA의 분자 배향에 대한 정보를 기본으로 위 분자들에 대한 흡착정보를 유추해내었다. 배향에 대한 정보를 위해 벤젠고리 모드, C-H 신축진동모드, carboxylate 음이온의 신축진동모드, 그리고 각각의 주요 작용기에 해당되는 모드들의 거동변화를 살펴보았으며 이로부터 m-BPCA는 thiol 그룹이 금속에 흡착되고 biphenyl 그룹이 기울어 서 있는 형태를 취하고 있고 나머지 분자들은 금속표면에 편평한 형태로 흡착됨을 알아내었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5017-5021
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• 2013

Objective: MicroRNAs (miRNAs) are a small class of non-coding, single-stranded RNAs with a critical role in genesis and maintenance of renal cancer mainly through binding to 3'-untranslated regions (3'UTR) of target mRNAs, which causes a block of translation and/or mRNA degradation. The aim of the present study was to investigate the potential effects of miR-122 in human renal cell carcinomas. Methods: The expression level of miR-122 was quantified by qRT-PCR. MTT, colony formation, invasion and migration assays were used to explore the potential functions of miR-122 in human renal cell carcinoma cells. Results: Cellular growth, invasion and migration in two A498 and 786-O cells were significantly increased after miR-122 transfection. Further experiments demonstrated that overexpression of miR-122 resulted in the increase of phospho-Akt (Ser473) and phospho-mTOR (Ser2448), then activation of mTOR targets, p70S6K and 4E-BP1. Conclusions: The up-regulation of miR-122 may play an important role in the progress of renal cancer through activating PI3K/Akt signal pathway and could be a potential molecular target for anti-cancer therapeutics.

• 천문학회보
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• 제44권1호
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• pp.86-86
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• 2019

We present BV photometric observations and high-resolution spectra of AO Ser, which were obtained at the Mt. Lemmon Optical Astronomy Observatory (LOAO) and the Bohyunsan Optical Astronomy Observatory (BOAO), respectively, in 2017. The radial velocities (RVs) for both components were measured, and the effective temperature of the primary star was found to be $T_{eff,1}=8,820{\pm}62K$ by a comparison of the observed spectra and the Kurucz models. A unique set of fundamental parameters of AO Ser were derived for the first time by a simultaneous analysis of the light and RV curves. The results indicate that our program target is a semi-detached eclipsing system with values of $M_1=2.06{\pm}0.11M_{\odot}$ and $M_2=0.41{\pm}0.03M_{\odot}$, $R_1=1.54{\pm}0.03R_{\odot}$ and $R_2=1.30{\pm}0.02R_{\odot}$, and $L_1=12.9{\pm}0.2L_{\odot}$ and $L_2=0.9{\pm}0.3L_{\odot}$. We applied multiple frequency analyses to the eclipse-subtracted light residuals. As a result, two frequencies of $f_1=21.85151days^{-1}$ and $f_2=23.48405days^{-1}$ were detected and their pulsation constants were calculated to $Q_1=0.0344days$ and $Q_2=0.0320days$. The pulsational characteristics and the position in the HR diagram demonstrate that the primary star is a ${\delta}$ Sct pulsator.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.49-57
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• 2024

While arterial tone is generally determined by the phosphorylation of Ser¹⁹ in myosin light chain (p-MLC2), Thr¹⁸/Ser¹⁹ diphosphorylation of MLC2 (pp-MLC2) has been suggested to hinder the relaxation of smooth muscle. In a dual-wire myography of rodent pulmonary artery (PA) and mesenteric artery (MA), we noticed significantly slower relaxation in PA than in MA after 80 mM KCl-induced condition (80K-contraction). Thus, we investigated the MLC2 phosphorylation and the expression levels of its regulatory enzymes; soluble guanylate cyclase (sGC), Rho-A dependent kinase (ROCK) and myosin light chain phosphatase target regulatory subunit (MYPT1). Immunoblotting showed higher sGC-α and ROCK2 in PA than MA, while sGC-β and MYPT1 levels were higher in MA than in PA. Interestingly, the level of pp-MLC2 was higher in PA than in MA without stimulation. In the 80K-contraction state, the levels of p-MLC2 and pp-MLC2 were commonly increased. Treatment with the ROCK inhibitor (Y27632, 10 µM) reversed the higher pp-MLC2 in PA. In the myography study, pharmacological inhibition of sGC (ODQ, 10 µM) slowed relaxation during washout, which was more pronounced in PA than in MA. The simultaneous treatment of Y27632 and ODQ reversed the impaired relaxation in PA and MA. Although treatment of PA with Y27632 alone could increase the rate of relaxation, it was still slower than that of MA without Y27632 treatment. Taken together, we suggest that the higher ROCK and lower MYPT in PA would have induced the higher level of MLC2 phosphorylation, which is responsible for the characteristic slow relaxation in PA.

• 한국잠사곤충학회지
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• 제6권
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• pp.1-8
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• 1966

각종 조건이 상수의 조장 1,000m당 엽량과 어떠한 관계가 있는가를 조사하였다. 1. 품종과의 관계 각 계통별 평균치에서는 106~109kg로 거의 차가 없으며 엽량의 계층별 분포상황은 Morus bombycis koidz. 계통이 가장 그 폭이 좁아서 60~160kg의 범위내에 있고 Morus Lhou(Ser.) koidz. 계통은 50~170kg, Morus alba L. 계통은 50~180kg의 범위내에 있다. 그러나 전품종의 79%는 80~140kg의 범위내에 있고 특히 Morus Lhou(Ser.) koidz. 계통은 그 85%가 이 범위내에 있다. 그리고 각 계통마다 1~2개의 Peak가 있으니 즉 Morus bombycis koidz.는 80~90kg와 120~140kg의 계층에 가장 많이 분포해 있고, Morus alba L. 계통은 90~100kg, Morus Lhou(Ser.) koidz. 계통은 100~110kg의 계층에 가장 많이 분포해 있다. 2. 정지법과의 관계 근예정지의 85kg에 대해서 다한식정지는 149kg로 근예정지에 비해서 75%가 더 많다. 3. 지조의 벌채정도와의 관계 무벌채구의 140kg에 대해 조장의 1/3벌채구는 166kg, $\frac{1}{2}$벌채구는 188kg로 무벌채구에 비해 각각 19%와 34%가 많았다. 그러나 이와같은 엽량의 증가는 주로 신소엽량중의 신소량의 증가에 기인하였다. 4. 지조의 세태와의 관계 동일 주내에 있어서 세조는 66kg, 중조는 80kg이었으나 유의차는 없었고, 태조는 150kg로 중조에 비해 88%나 더 많았다. 또 조경과의 관계에 있어서도 조경 10cm당 엽량에 있어서 세조는 811g, 중조는 875g이었으나 유의차는 없었고, 태조는 1,461g로 중조에 비해 67%나 더 많았다. 그리고 전지조의 평균은 1,201g이었다.

• Journal of Microbiology and Biotechnology
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• 제24권7호
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• pp.925-935
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• 2014

A cold-adapted carbohydrate esterase, CEST, belonging to the carbohydrate esterase family 6, was cloned from Microbulbifer thermotolerans DAU221. CEST was composed of 307 amino acids with the first 22 serving as a secretion signal peptide. The calculated molecular mass and isoelectric point of the mature enzyme were 31,244 Da and pH 5.89, respectively. The catalytic triad consisted of residues Ser37, Glu192, and His281 in the conserved regions: GQSNMXG, QGEX(D/N), and DXXH. The three-dimensional structure of CEST revealed that CEST belongs to the ${\alpha}/{\beta}$-class of protein consisted of a central six-stranded ${\beta}$-sheet flanked by eight ${\alpha}$-helices. The recombinant CEST was purified by His-tag affinity chromatography and the characterization showed its optimal temperature and pH were $15^{\circ}C$ and 8.0, respectively. Specifically, CEST maintained up to 70% of its enzyme activity when preincubated at $50^{\circ}C$ or $60^{\circ}C$ for 6 h, and 89% of its enzyme activity when preincubated at $70^{\circ}C$ for 1 h. The results suggest CEST belongs to group 3 of the cold-adapted enzymes. The enzyme activity was increased by $Na^+$ and $Mg^{2+}$ ions but was strongly inhibited by $Cu^+$ and $Hg^{2+}$ ions, at all ion concentrations. Using p-nitrophenyl acetate as a substrate, the enzyme had a $K_m$ of 0.278 mM and a $k_{cat}$ of $1.9s^{-1}$. Site-directed mutagenesis indicated that the catalytic triad (Ser37, Glu192, and His281) and Asp278 were essential for the enzyme activity.

• 생명과학회지
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• 제21권1호
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• pp.141-145
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• 2011

본 연구에서는 전사억제제(transcriptional inhibitor)로 알려진 actinomycin D가 전사조절인자(transcription factor)인 STAT의 인산화를 유도한다는 것을 확인하였다. Actinomycin D 처리 시 STAT1의 Tyr701, Ser727 인산화는 유도되지 않았지만 STAT3의 Tyr705 잔기의 인산화를 특이적으로 유도하는 것을 확인하였다. Actinomycin D에 의한 STAT3의 Tyr705 인산화 유도가 어떠한 기전을 통한 것인지 확인하기 위해서 관련 인자의 단백질 및 mRNA 발현을 확인한 결과 SOCS3의 단백질 및 mRNA 발현의 감소를 확인하였다. STAT3의 탈인산화를 유도한다고 알려진 tyrosine phosphatase인 SHP-1와 STAT의 upstream kinase인 JAK2의 인산화는 변화가 없었다. 또한 actinomycin D 뿐 아니라 다른 전사억제제인 DRB를 처리 하였을 경우에도 STAT3의 Tyr705 인산화가 유도되는 것을 확인하였다. 이상의 결과는 전사억제제에 의하여 특이적인 SOCS3 단백질 발현감소는 SOCS3의 하류의 target인 STAT3 인산화를 유도하였다.

• Applied Microscopy
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• 제23권2호
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• pp.53-77
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• 1993

In this study, an attempt was made to investigate the probable organelles participating in the secretion of biligrafin. The animals (ICR male mice, 25-30gm) were divided into normal control and 6 biligrafin injected groups to which 30% biligrafin (0.006ml/gm b.w.) were injected at 10, 20, 40, 80, 160 and 320 min prior to the sampling. The mice of each group were perfused through the heart with ice-cold 2.5% glutaraldehyde buffered with 0.1M Na-cacodylate (pH. 7.4) under the Na-pentobarbital (Nembtal 0.0015mg/gm b.w.) anesthesia and liver tissues were taken from each group. Some specimens were immersed 1 hr in the same solution used in the perfusion. After an overnight rinse in 0.1M Na-cacodylate buffer containing 10% DMSO and 7.6% sucrose, $75{\mu}m$ fronzen sections were made for cytochemical study. The sections were incubated in thiamin pyrophosphatase (TPPase) and inosine diphosphatase (ID Pase) media for 70 min at $37^{\circ}C$ respectively and acid phosphatase (AcPase) medium for 40 min at $37^{\circ}C$. They were postfixed in 1 % $OsO_4$ for 1 hr. The other specimens were immersed for 8 hrs in the fixative consisting of 2.5% glutaraldehyde and 3.0% paraformaldehyde buffered with Na-cacodylate (pH. 7.4). All of the osmificated specimens were processed for electron microscopy. In both normal and biligrafin injected groups, endoplasmic reticulum (ER), vacuoles, Golgi apparatus and lysosomes were seen in the vicinity of bile canaliculus. In the biligrafin injected groups, however, the Golgi apparatus appeared to be decreased and ER and vacuoles were dilated and increased. The rough endoplasmic reticulum (RER) having a few attached ribosomes appeared to be the round saccule, especially at 20 min after biligrafin injection. Smooth endoplasmic reticulum (SER) seemed to be formed by the detachment of ribosomes at the cisternal end of RER. The cistern of SER showed saccules which probably budded off to form the vacuole. The vacuoles were devoid of visible centents. This finding seemed to be in agreement with the biochemical property of the bile constituents. The fusion between the vacuoles and bile canaliculus were frequently seen in the groups injected with biligrafin. The lysosome did not show any changes in the biligrafin injected groups. Accumulation of some material and lipid droplets were seen at the 40 and 80 min after biligrafin injection, especially at the latter. At 160 and 320 min after biligrafin injections, however, they were decreased successively while the RER stack, free ribosomes and polysomes were increased. Although the reactive products of TPPase and IDPase were observed in the ER saccules and vesicles of the normal control and biligrafin injected groups, the fusion between the bile canaliculus and saccules or vesicles could easily be seen in the latter. The AcPase activity, however, was observed in the cistern at the maturing face of Golgi apparatus and lysosomes in both normal and biligrafin groups. The results suggest that the biligrafin is excreted via the vesicles, vacuoles or sacoules probably derived from the SER without the participation of Golgi apparatus and lysosomes, and the excess amount of material is stored as inclusions during the repairing of the organelles being overactive.