HMG-CoA 환원효소 억제제에 의한 ICAM-1 유전자의 발현조절

김현진,정효균,홍우정,김군순,조영석,김도희,채수흥,구본정,송민호,노흥규,김영건 충남대학교 의과대학 지역사회의학연구소 2001 충남의대잡지 Vol.28 No.1

Background : ICAM-1 act as one of major adhesion molecules in the atherosclerotic lesion. ICAM-1 expression is mainly regulated at the level of transcription and depend on IFN-γ signal transduction pathway in which the STAT1 transcrption factor is a critical intermediate. IFN-γreceptor not only initiates tyrosine 701 phosphorylation of STAT1 by Jak1 and Jak2, but also phosphorylates serine 727 through the activation of Raf-1/MAP kinases. HMG-CoA reductase inhibitors have anti-atherosclertic effects, beyond normalization of hypercholesterolemia, by directly acting on endothelial cells, macrophages and vascular smooth muscle cells. HMG-CoA reductase inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibition posttranslational farnesylation and geranyl-geranylation processing of small GTP-binding preoteins and inhibition of normal signaling activities. Method : We made several 5'-deletion constructs of rat ICAM-1 promoter and analyzed the promoter activities by measuring the luciferase activity after transfection into ECV304 cells and smooth muscle cells. We checked the level of total and phosphorylated STAT1 protein by immunoblot analysis using specific antibodies. Results : Lovastatin inhibits IFN-γ-induced ICAM-1 gene expression in the ECV304cell. The cells pretreated with PD98059, MEKK inhibitor showed significantly low ICAM-1 RNA induction with IFN-γ stimulatio. IFN-γ induced phosphorylation of tyrosine 701 was not significantly changed by the pretreatment of lovastatin. But lovastatin suppresses IFN-γ-induced phosphorylation of ERK1/ERK2 which are responsible for the seine 727 phosphorylation in STAT1. Conclusion : We showed that HMG-CoA reductase inhibitors, lovastatin, suppresses IFN-γ mediated ICAM-1 gene expression through the inhibition of transcription. HMG-CoA reductase inhibitor suppresses IFN-γ-induced phosphorylation of serine 727 in STAT1 through the modulation of MAP kinases.

혈청 Aminotransferase치의 만성적 상승을 보이면서 HBsAg 음성인 환자의 간조직 소견 : 지방간 환자에서 체중감량에 의한 간기능 검사의 개선효과 Effect of Weight Reduction on Aminotransferase Elevation

양석균,이영상,이효석,김정룡 대한내과학회 1992 대한내과학회지 Vol.42 No.2

HBsAg이 음성이면서 지속적으로 고 aminotransferase 혈증을 보이는 환자들의 임상적 의의는 잘 알려져 있지 않다. 저자 등은 AST치에 관계없이 6개월 이상 ALT치의 상승을 보인 HBsAg 음성 환자들 중 기왕력상 만성적 과다음주, 상습적 약물 복용 또는 당뇨병이 있는 환자들과 이학적 소견 및 내시경 검사상 간경변증의 소견을 보인 환자들을 제외한 102명을 대상으로 첫째, 간조직 검사를 통하여 지방석 간질환과 만성 활동성 간질환의 상대빈도를 알아내고 둘째, 이들을 감별할 수 있는 비침윤적 진단 지표를 찾아내고자 임상적, 생화학적 검사를 시행하여 다음과 같은 결과를 얻었다. 1) 대상환자 102명중 지방성 간질환이 66예(64.7%), 만성 활동성 간질환이 35예(34.3%) 이었으며 1예에서는 특이한 병리학적 소견을 볼 수 없었다. 2) 상대체중이 100% 미만인 환자들의 간질환은 만성 활동성 간질환일 확률이 높았고(100%), 120% 이상인 환자들은 만성 활동성 간질환의 유뭉에 관계없이 지방성 변화를 동반할 확률이 높았다(95.3%). 3) AST치가 정상범위 내에 있거나 ALT치가 정상의 2배 이하인 환자들의 간질환은 지방성 간질환일 확률이 높았고(94.6%), AST치가 정상의 3배를 넘거나 ALT치가 정상의 5배를 넘는 경우는 만성 활동성 간질환일 확률이 높았다(87.5%). 4) Alkaline phosphatase가 증가한 경우 또는 혈소판수가 감소한 경우의 간질환이 만성 활동성 간질환일 확률은 각각 77.8%, 90.9%이었다. 5) 3㎏ 이상 체중 감량이 가능하였던 지방성 간질환 환자 29예 모두에서 ALT치의 감소를 보엿고 이 중 25예에서 ALT치가 정상범위 내로 감소하였다. 이상의 결과로 상대체중, AST, ALT, alkaline phosphatase, 혈소판수 및 체중 감량의 시도는 일부 환자에서 지방성 간질환과 만성 활동성 간질환의 감별진단에 유용하다고 생각된다. 그러나 상대체중이 100~120%이고 AST치가 정상의 1~3배이며 ALT치가 정상의 2~5배인 경우는 간조직 검사에 의해서만 감별이 가능하다고 판단되며, 이러한 겨우에 최근에 개발되어 임상적 사용이 가능한 C형 간염 바이러스 항체의 검출이 감별진단에 얼마나 유용하지에 대해서는 좀더 많은 연구가 필요하리라 생각된다. The nature of chronic aminotransferase elevations in HBsAg-negative patients has not been well known. The present study was designed to determine the relative frequencies of fatty liver disease (FLD) and chronic active liver disease (CALD) in 102 HBsAg-negative patients whose alanine aminotransferase (ALT) levels were abnormally elevated for more than 6 months regardless of aspartate aminotransferase (AST) levels. We have also evaluated clinical and laboratory investigative procedures including relative body weight (RBW) to suggest noninvasive diagnostic parameters which can be useful in discriminating FLD from CALD. Standard body weight (SBW) was calculated by the following equation: SBW(㎏)= [Height (㎝)-100] × 0.9 Those with histories of excessive alcohol consumption, drug abuse or diabetes mellitus, or with physical and endoscopic signs of liver cirrhosis were excluded. The results were summarized as follows: 1) Of all 102 cases, FLD was found in 66 cases (64.7%) and CALD in 35 cases (34.3%). In one case, there was no specific pathological finding. 2) The patients whose RBWs were below 100% were likely to have CALD (positive predictive value (PPV) = 100%). and those whose RBWs were 120% or more were apt to have fatty changes regardless of preexisting CALD (PPV=95.3%). 3) The patients whose AST levels were within normal range or whose ALT levels were below two times of upper normal limit were probable to have FLD (PPV=94.6%), while those whose AST levles were over three times or ALT levels over five times of upper normal limit had more chances to have CALD (PPV=87.5%) 4) Abnormally increased alkaline phosphatase levels were found in 1.5% and 28.696, and abnormally decreased platelet counts in 3.0% and 20.0% of patients with FLD and CALD, respectively. PPVs of abnormal alkaline phosphatase levels and platelet counts were 77.8% and 90.0%, respectively. 5) All of 29 cases with FLD who lost 3 ㎏ or more of their body weights showed improvement in ALT level;25 of these cases showed normalization of ALT level. In conclusion, RBW, AST, ALT, alkaline phosphatase levels or platelet counts, and trial of body weight reduction may be useful in the differential diagnosis of FLD and CALD in some selected cases; however, differentiation in patients with RBWs between 100% and 120%, and with AST between one and 3 times and ALT between 2 and 5 times of upper normal limit is possible only by liver biopsy.

Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis

Chung, Hyo Kyun,Ryu, Dongryeol,Kim, Koon Soon,Chang, Joon Young,Kim, Yong Kyung,Yi, Hyon-Seung,Kang, Seul Gi,Choi, Min Jeong,Lee, Seong Eun,Jung, Saet-Byel,Ryu, Min Jeong,Kim, Soung Jung,Kweon, Gi Rya The Rockefeller University Press 2017 The Journal of cell biology Vol.216 No.1

<P>Reduced mitochondrial electron transport chain activity promotes longevity and improves energy homeostasis via cell-autonomous and –non-autonomous factors in multiple model systems. This mitohormetic effect is thought to involve the mitochondrial unfolded protein response (UPR<SUP>mt</SUP>), an adaptive stress-response pathway activated by mitochondrial proteotoxic stress. Using mice with skeletal muscle–specific deficiency of <I>Crif1</I> (muscle-specific knockout [MKO]), an integral protein of the large mitoribosomal subunit (39S), we identified growth differentiation factor 15 (GDF15) as a UPR<SUP>mt</SUP>-associated cell–non-autonomous myomitokine that regulates systemic energy homeostasis. MKO mice were protected against obesity and sensitized to insulin, an effect associated with elevated GDF15 secretion after UPR<SUP>mt</SUP> activation. In <I>ob</I>/<I>ob</I> mice, administration of recombinant GDF15 decreased body weight and improved insulin sensitivity, which was attributed to elevated oxidative metabolism and lipid mobilization in the liver, muscle, and adipose tissue. Thus, GDF15 is a potent mitohormetic signal that safeguards against the onset of obesity and insulin resistance.</P>

Holter 심전도 모니터를 이용한 만성 폐쇄성 폐질환 환자에 있어서의 부정맥에 대한 연구 - 만성 폐쇄성 폐질환에 있어서의 부정맥에 대한 연구

이정균 ( Chung Kyun Lee ),이정희 ( Chung Hee Lee ),박성수 ( Sung Soo Park ),이방헌 ( Bang Hun Lee ),주상언 ( Sang Aun Joo ),김순길 ( Soon Gill Kim ),신승호 ( Seung Ho Shin ),황흥곤 ( Hweung Kon Hwang ),정효철 ( Hyo Chul Chung ) 대한내과학회 1984 대한내과학회지 Vol.27 No.11

STRUCTURAL CHANGE OF POLYDOMAIN IN THE LIQUID CRYSTALLINE POLYMERS BY WEAK SHEAR FLOW

Chung, In Jae,Kim, Kwang Man,Kim, Tae Kyun,Kim, Sang Hyo 한국화학공학회 1997 Korean Journal of Chemical Engineering Vol.14 No.1

Steady-state shear stress (τ-_(12)) and first normal stress difference (N₁) of liquid crystalline polymers at low shear rates were examined by using a mesoscopic constitutive equation set including the idea of initial domain size. For the applicability to the weak shear flow at low shear rates, a Hinch-Leal closure approximation was adopted in the calculation of the constitutive equation set. The steady-state rheological behaviors predicted by adopting the Hinch-Leal approximation were compared with those by the Doi simple decoupling approximation. It could be predicted from the plot of N₁, versus τ-_(12) that smaller domains distributed isotropically at a quiescent state might maintain the isotropic domain distribution even at the imposition of moderate shear rate, and then could be changed to the ordered (or partially elongated) domain phase by a further increase of shear rate. Such change of the polydomain structure with the increase in shear rate could be proved more precisely by the transient rheological behaviors of N₁, and τ-_(12) after the start-up of shear flow.

Crown-Ether End-Capped Carbosiloxane Dendrimers

Kim, Chung-Kyun,Kim, Hyo-Jeong Korean Chemical Society 2002 Bulletin of the Korean Chemical Society Vol.23 No.4

Preparation and Unequivocal Identification of Chromophores-Substituted Carbosilane Dendrimers up to 7^th Generations

Kim, Chung-Kyun,Kim, Hyo-Jung,Oh, Myeong-Jin,Hong, Jang-Hwan Korean Chemical Society 2009 Bulletin of the Korean Chemical Society Vol.30 No.4

Bis(phenylethynyl)dimethylsilane is branched by the hydrosilation of the phenylethynyl group with dichloromethylsilane, and then the resulting chlorosilane is reacted with lithium phenylacetylide to give the $1^{st}$ generation. The same hydrosilation and alkynylation are repeated to obtain the $7^{th}$ generation. In addition peripheral Si-Cl moiety of the seven kind generation dendrimers are reacted with alcoholic moiety of 9-hydroxymethylanthracene and 2-(2-hydroxyphenyl)benzoxazole group in the presence of TMEDA. Then three kinds of carbosilane dendrimers are prepared from the $1^{st}$ to the $7^{th}$ generations, the $7^{th}$ generation of each dendrimer has 256 phenylethynyl, 256 9-anthracenylmethoxy, or 128 2-(2-phenoxy)benzoxazole groups. Each synthesized dendrimer is unequivocally characterized by $^1H\;and\;^{13}C\;NMR$, elemental analysis, MALDI-MS, GPC, and PL (photoluminescence). Characteristically PDI (Polydisperse Index) values of the dendrimers’ peak in GPC are in the range of $1.00{\sim}1.07$, which indicates that each generation of carbosilane is in unified distribution. PL spectra of phenylethynyl and 9- anthracenemethoxy group substituted dendrimers show no significant change with increasing the generation from the $1^{st}$ to the $7^{th}$. However, the PL spectra of 2-(2-phenoxy)benzoxazole group substituted dendrimers show a blue-shift trend with increasing the generation from the $1^{st}$ to the $7^{th}$.

Mepivacaine-induced contraction involves phosphorylation of extracellular signal-regulated kinase through activation of the lipoxygenase pathway in isolated rat aortic smooth muscle

Lee, Hyo Min,Ok, Seong-Ho,Sung, Hui-Jin,Eun, So Young,Kim, Hye Jung,Lee, Soo Hee,Kang, Sebin,Shin, Il-Woo,Lee, Heon Keun,Chung, Young-Kyun,Choi, Mun-Jeoung,Bae, Sung Il,Sohn, Ju-Tae Canadian Science Publishing 2013 Canadian journal of physiology and pharmacology Vol.91 No.4

<P> Mepivacaine is an aminoamide local anesthetic with an intermediate duration that intrinsically produces vasoconstriction both in vivo and in vitro. This study investigated the arachidonic acid metabolic pathways involved in mepivacaine-induced contraction, and elucidated the associated cellular mechanism with a particular focus on extracellular signal-regulated kinase (ERK) in endothelium-denuded rat aorta. Isolated rat thoracic aortic rings were suspended for isometric tension recording. Cumulative mepivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, indomethacin, NS-398, SC-560, fluconazole, PD 98059, and verapamil. Mepivacaine-induced ERK phosphorylation, 5-lipoxygenase (5-LOX) expression, and cyclooxygenase (COX)-2 expression in rat aortic smooth muscle cells were detected by Western blot analysis in the presence or absence of inhibitors. Mepivacaine produced tonic contraction in isolated endothelium-denuded rat aorta. Quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, NS-398, PD 98059, and verapamil attenuated mepivacaine-induced contraction in a concentration-dependent manner. However, fluconazole had no effect on mepivacaine-induced contraction. PD 98059, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, and indomethacin attenuated mepivacaine-induced ERK phosphorylation. Mepivacaine upregulated 5-LOX and COX-2 expression. These results suggest that mepivacaine-induced contraction involves ERK activation, which is primarily mediated by the 5-LOX pathway and in part by the COX-2 pathway. </P>

에탄올이 신경아세포종 B103세포의 Protein Kinase C Isozyme 활성에 미치는 영향

조효정(Hyo-Jung Cho),정영진(Young-Jin Chung),진승하(Sung-Ha Jin),오우균(Woo-Kyun Oh),김상원(Sang-Won Kim),강은정(Eun-Jung Kang),박진규(Jin-kju Park) 한국식품영양과학회 2004 한국식품영양과학회지 Vol.33 No.2

에탄올이 지속적으로 뇌 신경세포에 미치는 영향을 조사하기 위하여 흰쥐의 신경세포로부터 유래 된 B103 neuroblastoma cell을 사용하여 세포독성이 나타나지 않는 에탄올 농도(0, 50, 100, 200 mM)에서의 1, 2, 8, 18, 24시간 경과에 따라 유도되는 PKC α, γ, ε, ζ isozyme들의 양을 세포질분획과 세포막 분획으로 나누어 Western blot으로 각각 분석하였다. 100 mM의 에탄올 농도에서 분석된 PKC isozyme들 중 PKC-γ는 18시간대의 세포질에서, 그리고 PKC-ε은 8~18시간대의 세포막분획에서 각각 현저한 유도현상을 보였다. PKC-α는 200 mM의 에탄올 첨가 후 18시간과 24시간에 세포질과 세포막 분획에서 모두 대조군의 150%까지 현저한 증가를 나타낸 반면 PKC-ζ는 100, 200 mM 에탄올 농도에서 배양(18, 24시간 동안)한 세포의 세포막분획에서만 유도되었다. 그리고 50, 100, 200 mM의 에탄올 농도에서 24시간동안 배양한 세포질 분획에서 PKC-γ는 농도 의존적으로 감소하여 200 mM의 에탄올 농도에서는 대조군의 47%까지 현저한 감소를 나타내었으며, 세포내에 세포독성을 나타내지 않는 농도 특히 100~200 mM 농도범위의 에탄올을 첨가하여 24시간 동안 지속적으로 배양할 때 PKC-γ 및 ε이 관련된 신호전달체계가 억제됨을 보였다. 이는 에탄올이 PKC isozyme들의 상호간 조절을 통해 신호전달계 또는 신경전달 물질들의 변화에 영향을 줄 수 있음을 시사하며 에탄올의 중추신경계에 미치는 지속적 영향으로 나타나는 행동장애 및 뇌기능의 손상 또는 보호과정에 PKC-isozyme들이 관여할 수 있음을 시사한다. It is well known that long-term heavy ethanol intake causes alcoholic dementia, cerebellar degeneracy or Wernicke-Korsakoff syndrome and aggravates the conditions of many other neuro-psychotic disorders. Recently it is indicated that protein kinase C (PKC) plays an important role in the action of ethanol and in the neuro-adaptational mechanisms under chronic ethanol exposure. In order to investigate the effect of ethanol on PKC isoforms levels within the range of not showing any cytotoxicity, B103 neuroblastoma cell line transformed from murine central nervous system was employed and western blot analysis was carried out by using PKC isoform-specific antibodies. The changes of PKC-α, γ, ε and ζ level in the range of ethanol concentration 50~200 mM were examined at the exposure time 1, 2, 8, 18 and 24 hrs in both cytosolic and membrane fraction. A typical ethanol concentration inducing the PKC isozymes was 100 mM, and the transforming time ranges of PKC isozymes could be considered as two different parts to each PKC isoform such as initial (0~2 hrs) and prolonged (8~24 hrs) stages. PKC-γ and PKC-ε were clearly induced during the prolonged stages in cytosol at 18 hrs, and membrane fraction at 8 hrs and 18 hrs, respectively. On the other hand the PKC-α and PKC-ζ isozymes were largely induced in the prolonged stages at 18 hrs and 24 hrs, where the PKC-α isozyme was induced in both cytosol and membrane fractions at 200 mM ethanol concentration while the PKC-ζ isozyme was induced only in the membrane fractions at 100, 200 mM. At 200 mM ethanol concentration of 24 hrs incubation in the prolonged stage, the PKC-α was maximally induced by 150% of the control values whereas the PKC-γ was significantly decreased to 47% of the control values. These results suggest that 100~200 mM ethanol may modulate the signal transduction and neurotransmitter release in the central nervous system through the regulation of PKC isozymes, and the action of these isoforms may act differently each other in the cell.

Control and Design of a Arc Power Supply for KSTAR’s the Neutral Beam Injection

Dong-Kyun Ryu,Hee-Jun Lee,Jung-Hyo Lee,Chung-Yuen Won 대한전기학회 2015 Journal of Electrical Engineering & Technology Vol.10 No.1

The neutral beam injection generate ultra-high temperature energy in the tokamak of nuclear fusion. The neutral beam injection make up arc power supply, filament power supply and acceleration & deceleration power supply. The arc power supply has characteristics of low voltage and high current. Arc power supply generate arc through constant output of voltage and current. So this paper proposed suitable buck converter for low voltage and high current. The proposed buck converter used parallel switch because it can be increased capacity and decrease conduction loss. When an arc generated, the neutral beam injection chamber occur high voltage. And it will break output capacitor of buck converter. Therefore the output capacitor was removed in the proposed converter. Thus the proposed converter should be designed for the characteristics of low voltage and high current. Also, the arc power supply should be guaranteed for system stability. The proposed parallel buck converter enables the system stability of the divided low output voltage and high current. The proposed converter with constant output be the most important design of the output inductor. In this paper, designed arc power supply verified operation of system and stability through simulation and prototype. After it is applied to the 288[kW] arc power supply for neutral beam injection.