Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation

Kim, Soo Jeong,Ryu, Min Jeong,Han, Jeongsu,Jang, Yunseon,Kim, Jungim,Lee, Min Joung,Ryu, Ilhwan,Ju, Xianshu,Oh, Eungseok,Chung, Woosuk,Kweon, Gi Ryang,Heo, Jun Young Academic Press 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>The derangement of tyrosine hydroxylase (TH) activity reduces dopamine synthesis and is implicated in the pathogenesis of Parkinson's disease. However, the extracellular modulator and intracellular regulatory mechanisms of TH have yet to be identified. Recently, high-mobility group box 1 (HMGB1) was reported to be actively secreted from glial cells and is regarded as a mediator of dopaminergic neuronal loss. However, the mechanism for how HMGB1 affects TH expression, particularly through the receptor for advanced glycation endproducts (RAGE), has not yet been investigated. We found that recombinant HMGB1 (rHMGB1) upregulates TH mRNA expression via simultaneous activation of JNK phosphorylation, and this induction of TH expression is blocked by inhibitors of RAGE and JNK. To investigate how TH expression levels change through the HMGB1-RAGE axis as a result of MPP<SUP>+</SUP> toxicity, we co-treated SN4741 dopaminergic cells with MPP<SUP>+</SUP> and rHMGB1. rHMGB1 blocked the reduction of TH mRNA following MPP<SUP>+</SUP> treatment without altering cell survival rates. Our results suggest that HMGB1 upregulates TH expression to maintain dopaminergic neuronal function via activating RAGE, which is dependent on JNK phosphorylation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Activation of HMGB1-RAGE stimulates the TH expression in dopaminergic neuron cells. </LI> <LI> HMGB1 regulates TH expression via phosphorylation of JNK. </LI> <LI> HMGB1 rescues the TH expression without alteration of cell viability in MPP<SUP>+</SUP> treated dopaminergic neuron cells. </LI> </UL> </P>

Stearoyl CoA desaturase (SCD) facilitates proliferation of prostate cancer cells through enhancement of androgen receptor transactivation

Kim, Seung-Jin,Choi, Hojung,Park, Sung-Soo,Chang, Chawnshang,Kim, Eungseok Springer-Verlag 2011 Molecules and cells Vol.31 No.4

Metformin Inhibits Nuclear Receptor TR4–Mediated Hepatic Stearoyl-CoA Desaturase 1 Gene Expression With Altered Insulin Sensitivity

Kim, Eungseok,Liu, Ning-Chun,Yu, I-Chen,Lin, Hung-Yun,Lee, Yi-Fen,Sparks, Janet D.,Chen, Lu-Min,Chang, Chawnshang American Diabetes Association 2011 Diabetes Vol.60 No.5

<P><B>OBJECTIVE</B></P><P>TR4 is a nuclear receptor without clear pathophysiological roles. We investigated the roles of hepatic TR4 in the regulation of lipogenesis and insulin sensitivity in vivo and in vitro.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>TR4 activity and phosphorylation assays were carried out using hepatocytes and various TR4 wild-type and mutant constructs. Liver tissues from TR4 knockout, C57BL/6, and <I>db/db</I> mice were examined to investigate TR4 target gene stearoyl-CoA desaturase (<I>SCD</I>) 1 regulation.</P><P><B>RESULTS</B></P><P>TR4 transactivation is inhibited via phosphorylation by metformin-induced AMP-activated protein kinase (AMPK) at the amino acid serine 351, which results in the suppression of SCD1 gene expression. Additional mechanistic dissection finds TR4-transactivated <I>SCD1</I> promoter activity via direct binding to the TR4-responsive element located at −243 to −255 on the promoter region. The pathophysiological consequences of the metformin→AMPK→TR4→SCD1 pathway are examined via TR4 knockout mice and primary hepatocytes with either knockdown or overexpression of TR4. The results show that the suppression of <I>SCD1</I> via loss of TR4 resulted in reduced fat mass and increased insulin sensitivity with increased β-oxidation and decreased lipogenic gene expression.</P><P><B>CONCLUSIONS</B></P><P>The pathway from metformin→AMPK→TR4→SCD1→insulin sensitivity suggests that TR4 may function as an important modulator to control lipid metabolism, which sheds light on the use of small molecules to modulate TR4 activity as a new alternative approach to battle the metabolic syndrome.</P>

Detection of an Impact Flash Candidate on the Moon with an Educational Telescope System

Kim, Eunsol,Kim, Yong Ha,Hong, Ik-Seon,Yu, Jaehyung,Lee, Eungseok,Kim, Kyoungja The Korean Space Science Society 2015 Journal of Astronomy and Space Sciences Vol.32 No.2

At the suggestion of the NASA Meteoroid Environment Office (NASA/MEO), which promotes lunar impact monitoring worldwide during NASA's Lunar Atmosphere and Dust Environment Explorer (LADEE) mission period (launched Sept. 2013), we set up a video observation system for lunar impact flashes using a 16-inch educational telescope at Chungnam National University. From Oct. 2013 through Apr. 2014, we recorded 80 hours of video observation of the unilluminated part of the crescent moon in the evening hours. We found a plausible candidate impact flash on Feb. 3, 2014 at selenographic longitude $2.1^{\circ}$ and latitude $25.4^{\circ}$. The flash lasted for 0.2 s and the light curve was asymmetric with a slow decrease after a peak brightness of $8.7{\pm}0.3mag$. Based on a star-like distribution of pixel brightness and asymmetric light curve, we conclude that the observed flash was due to a meteoroid impact on the lunar surface. Since unequivocal detection of an impact flash requires simultaneous observation from at least two sites, we strongly recommend that other institutes and universities in Korea set up similar inexpensive monitoring systems involving educational or amateur telescopes, and that they collaborate in the near future.

보의 설치에 따른 하천수질변화 분석

김응석(Eungseok Kim),이승현(Seunghyun Lee) 한국방재학회 2022 한국방재학회논문집 Vol.22 No.3

There has been an increase in the amount of pollutants such as biochemical water and factory wastewater discharged from urban areas as a result of urbanization and industrialization. Therefore, research on securing water resources and improving water quality in rivers around cities is being actively conducted. This study analyzed the pattern of change of water quality due to the installation of overflow type weirs among the hand structures in the existing river. The target watershed was performed at Gilancheon, located in Andong-si, Gyeongsangbuk-do. The flow coefficient was calculated by analyzing the flow velocity and water level according to weir installation using the HEC-RAS. Afterwards, the QUALKO model was built, and the water quality analysis according to weir installation was performed by applying the flow coefficient calculated using HEC-RAS. As a result of the analysis, the flow rate was found to have decreased, and a stagnation section occurred due to the influence of weir installation, resulting in an increase in Chl-a. Due to the increase of Chl-a, BOD increased by 29%-32%, and T-N and T-P, which are nutrients for Chl-a, decreased. Therefore, an increase in Chl-a concentration due to weir installation can cause eutrophication due to the growth of green algae in the river, and it is believed that it can greatly affect the deterioration of water quality. Furthermore, it is considered that it will be able to help predict changes in water quality for the installation and operation of weirs in the future. 도시화 및 산업화로 인해 도시지역에서 배출되는 생화하수, 공장 폐수 등의 오염물질의 발생량 증가로 도시주변 하천의 수자원 확보 및 수질개선에 대한 연구가 활발히 진행되어지고 있다. 따라서 본 연구에서는 기존 하천에 수공구조물 중 월류형보를 설치에 따른 수질변화 양상을 분석하였다. 대상유역은 경상북도 안동시에 위치한 길안천을 대상으로 수행하였다. HEC-RAS를 이용하여 보 설치에 따른 유속 및 수위 등을 분석하여 유량계수를 산정하였다. 이후 QUALKO 모형을 구축하였으며, 보 설치에 따른 수질분석은 HEC-RAS를 이용해 산정한 유량계수를 적용하여 분석을 수행하였다. 분석결과 보 설치의 영향으로 인해 유속 감소 및 정체구간이 발생되어 Chl-a가 증가하게 된다. Chl-a의 증가로 인해 BOD의 경우 29~32% 증가하며, Chl-a에 영양분이 되는 T-N, T-P의 경우 감소되는 양상을 나타내었다. 따라서 보 설치에 따른 Chl-a 농도증가는 하천에 녹조류 번식으로 인한 부영양화를 발생시킬 수 있으며, 수질악화에 큰 영향을 미칠 수 있을 것으로 판단된다. 추후 보 설치 및 운영에 대한 수질변화 예측에 도움을 줄 수 있을 것으로 판단된다.

Department of High and Applied Mathematics, Odessa National Maritime University with an Educational Telescope System

Eunsol Kim,Yong Ha Kim,Ik-Seon Hong,Jaehyung Yu,Eungseok Lee,Kyoungja Kim 한국우주과학회 2015 Journal of Astronomy and Space Sciences Vol.32 No.2

At the suggestion of the NASA Meteoroid Environment Office (NASA/MEO), which promotes lunar impact monitoring worldwide during NASA’s Lunar Atmosphere and Dust Environment Explorer (LADEE) mission period (launched Sept. 2013), we set up a video observation system for lunar impact flashes using a 16-inch educational telescope at Chungnam National University. From Oct. 2013 through Apr. 2014, we recorded 80 hours of video observation of the unilluminated part of the crescent moon in the evening hours. We found a plausible candidate impact flash on Feb. 3, 2014 at selenographic longitude 2.1° and latitude 25.4°. The flash lasted for 0.2 s and the light curve was asymmetric with a slow decrease after a peak brightness of 8.7 ± 0.3 mag. Based on a star-like distribution of pixel brightness and asymmetric light curve, we conclude that the observed flash was due to a meteoroid impact on the lunar surface. Since unequivocal detection of an impact flash requires simultaneous observation from at least two sites, we strongly recommend that other institutes and universities in Korea set up similar inexpensive monitoring systems involving educational or amateur telescopes, and that they collaborate in the near future.

Detection, Identification and Characterization of In vitro GSH Metabolites Formed by 1- and 2-Bromopropane

Lee EungSeok,Moon YoonSoo,Kim EunKyung,Basnet Arjun,Zhao LongXuan,Kim DaeOk,Kim NamHee,Chae Whigun,Jeong TaeCheon 大韓藥學會 2003 大韓藥學會 總會 및 學術大會 Vol.2003 No.2

홍수취약성과 홍수피해잠재능을 이용한 도시지역 평가비교

김응석(Eungseok Kim),이승현(Seunghyun Lee ) 한국방재학회 2022 한국방재학회논문집 Vol.22 No.5

최근 기후변화와 급격한 도시화, 빈번히 발생되는 게릴라성 집중호우로 인해 도시 홍수피해가 급증하고 있다. 따라서 도시지역의홍수와 관련되어 효과적인 정책수립에 필요한 정량적인 홍수 피해분석 기법이 필요하다. 본 연구에서는 도시지역을 대상으로홍수피해 정도를 분석하는 대표적인 방법인 홍수취약성 방법과 홍수피해잠재능(PFD) 방법을 적용 하였다. 또한, 홍수방어시설용량-피해(PCD) 매트릭스 기법을 이용하여 각 분석 방법별 결과를 비교 분석하였다. PCD 매트릭스 기법은 기존의 홍수방어시설이 많이 건설되어 있어도 관리 미흡 또는 설계강우 이상의 호우가 발생시에는 홍수피해가 클 수 있다는 것을 직관적으로보여주는 기법이다. 기존의 홍수피해 기법 2개를 적용한 결과에서는 서초구는 재정자립도가 높고 홍수피해 방어시설물이많은 구축되어 있어서 홍수취약성이 낮은 것으로 산정되었다. 그러나 PCD 매트릭스를 적용한 결과에서 서초구는 홍수취약성이높게 분류되었다. 따라서 이러한 상반된 결과에서 보듯이 홍수방어 정책 수립시에는 보다 세밀한 검토 및 분석이 필요할것으로 판단되었다. Recently, urban flood damage has rapidly increased due to climate change, rapid urbanization, and frequent guerrilla heavy rains. Therefore, a quantitative flood damage analysis technique is required for effective policy regarding flooding in urban areas. In this study, the flood vulnerability and potential flood damage (PFD) methods, which are representative methods for analyzing the degree of flood damage in urban areas, were applied. In addition, the results of each analysis method were compared and analyzed using the flood prevention capacity-damage (PCD) matrix technique, which intuitively shows that even if many existing flood protection facilities are built, flood damage can be large when there is insufficient management or heavy rainfall exceeding the design rainfall occurs. The two existing flood damage techniques estimated Seocho-gu to have low flood vulnerability due to high financial independence and many flood damage protection facilities. However, application of the PCD matrix resulted in classifying Seocho-gu as highly vulnerable to flooding. These conflicting results thus demonstrate that a more detailed review and analysis are necessary when establishing a flood protection policy.

Dysport and Botox at a Ratio of 2.5:1 Units in Cervical Dystonia: A Double-Blind, Randomized Study

Yun, Ji Young,Kim, Jae Woo,Kim, Hee-Tae,Chung, Sun Ju,Kim, Jong-Min,Cho, Jin Whan,Lee, Jee-Young,Lee, Ha Neul,You, Sooyeoun,Oh, Eungseok,Jeong, Heejeong,Kim, Young Eun,Kim, Han-Joon,Lee, Won Yong,Jeon BlackWell Publishing Ltd 2015 Movement disorders Vol.30 No.2

<P>We aimed to compare Dysport (abobotulinumtoxinA, Ipsen Biopharm, Slough, UK) and Botox (onabotulinumtoxinA, Allergan, Irvine, CA, USA) at a 2.5:1 ratio in the treatment of cervical dystonia (CD). A Dysport/Botox ratio of lower than 3:1 was suggested as a more appropriate conversion ratio, considering its higher efficacy and more frequent incidence of adverse effects not only in the treatment of CD but also in other focal movement disorders. A randomized, double-blind, multicenter, non-inferiority, two-period crossover study was done in CD, with a duration of at least 18 months. Patients were randomly assigned to treatment for the first period with Dysport or Botox, and they were followed up for 16 weeks after the injection. After a 4-week washout period, they were switched to the other formulation and then followed up for 16 weeks. The primary outcome was the changes in the Tsui scale between the baseline value and that at 1 month after each injection. A total of 103 patients were enrolled, and 94 completed the study. Mean changes in the Tsui scale between baseline and 4 weeks after each injection tended to favor Botox; however, this was not statistically significant (4.0 ± 3.9 points for the Dysport treatment vs. 4.8 ± 4.1 points for Botox; 95% confidence interval, −0.1-1.7; <I>P</I> = 0.091). The mean change of the Toronto western spasmodic torticollis rating scale score, the proportion of improvement in clinical global impression and patient global impression, and the incidences of adverse events were not significantly different between the two treatments. With regard to safety and efficacy, Dysport was not inferior to Botox in patients with CD at a conversion factor of 2.5:1. [http//clinicaltrial.gov: NCT00950664] © The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</P>

FXRalpha Down-Regulates LXRalpha Signaling at the CETP Promoter via a Common Element.

Park, Sung-Soo,Choi, Hojung,Kim, Seung-Jin,Kim, Ok Jin,Chae, Kwon-Seok,Kim, Eungseok Korean Society for Molecular Biology 2008 Molecules and cells Vol.26 No.4

<P>The cholesteryl ester transfer protein (CETP), a key player in cholesterol metabolism, has been shown to promote the transfer of triglycerides from very low density lipoprotein (VLDL) and low density lipoprotein (LDL) to high density lipoprotein (HDL) in exchange for cholesterol ester. Here we demonstrate that farnesoid X receptor alpha (FXR alpha; NR1H4) down-regulates CETP expression in HepG2 cells. A FXR alpha ligand, chenodeoxycholic acid (CDCA), suppressed basal mRNA levels of the CETP gene in HepG2 cells in a dose-dependent manner. Using gel shift and chromatin immunoprecipitation (ChIP) assays, we found that FXR alpha could bind to the liver X receptor alpha (LXR alpha; NR1H3) binding site (LXRE; DR4RE) located within the CETP 5' promoter region. FXRalpha suppressed LXRalpha-induced DR4RE-luciferase activity and this effect was mediated by a binding competition between FXRalpha and LXRalpha for DR4RE. Furthermore, the addition of CDCA together with a LXR alpha ligand, GW3965, to HepG2 cells was shown to substantially decrease mRNA levels of hepatic CETP gene, which is typically induced by GW3965. Together, our data demonstrates that FXRalpha down-regulates CETP gene expression via binding to the DR4RE sequence within the CETP 5' promoter and this FXRalpha binding is essential for FXRalpha inhibition of LXRalpha -induced CETP expression.</P>