Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>

3,4,5-Trihydroxycinnamic Acid Inhibits Lipopolysaccharide-Induced Inflammatory Response through the Activation of Nrf2 Pathway in BV2 Microglial Cells

( Jae Won Lee ),( Yong Jun Choi ),( Jun Ho Park ),( Jae Young Sim ),( Yong Soo Kwon ),( Hee Jae Lee ),( Sung Soo Kim ),( Wan Joo Chun ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.1

3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-a, and IL-1b. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.

강원남부 폐광지역 개발기금 사업의 경제적 효과 : 2001~2021년간의 기금사업을 중심으로

유원근(Won Keun Yu),최호영(Ho-yeong Choi),김승렬(Seung-Leul Kim) 한국산학기술학회 2022 한국산학기술학회논문지 Vol.23 No.11

본 논문은 2001년부터 2021년 기간의 강원남부 폐광지역 4개 시군을 대상으로 전개된 폐광지역개발기금 투자의 경제적 파급효과를 실증적으로 분석함을 목적으로 한다. 이 기간 동안 연차별 투자 건수 1,220개로 구성된 691개의 재원 사업이 이행되었다. 분석대상 기간 동안 연차별로 투자된 재원의 합계는 총 1조 6,180.5억원이며, 지역산업연관분석을 통해 실증적으로 경제적 파급효과를 도출하는 것이 본고의 목적이다. 폐광지역개발기금의 투자금액의 면에서 보면, 대체로 생산유발효과가 상대적으로 낮은 3차산업 부문에 대한 재원의 비중이 큰 것으로 나타났다. 그러나 다른 한편으로 고려해야 할 점은 3차산업 부문의 취업유발효과가 이 지역에서 타 산업에 비해 높다는 점이다. 이러한 산업구조적 특성을 토대로 향후 폐광지역개발기금 사업의 경제적 효과를 최적화시키기 위해서는 유발계수 값의 분포를 고려한 재원의 배분 계획을 마련할 필요가 있다. 본고의 추정결과는 향후 폐광지역 개발기금의 합리적인 배분을 위한 실증적 기초 자료로서의 역할을 할 것으로 기대된다. This study aimed to analyze the economic effects of the closed mine area development fund on the southern part of the Gangwon provinces during the period 2001~2021. In this time frame, 691 financial projects comprising 1,220 items in the annual base were carried out and the total amount of investment was 1,618.05 billion Won. The main goal of this study was to derive empirical evidence about the economic effect of this fund through the regional industrial input-output tables. An analysis of the distribution of financial resources available to the specific fields revealed that the portion of funds invested in the tertiary industry sector has a low production inducement effect, which was not comparable with other industries. However, the movement of the employment inducement coefficient of tertiary industries led by the services sector in this area is comparatively high. Based on the regional character of the industrial structure, it is necessary to make a deliberate funds distribution plan taking the movement of the above inducement coefficients into consideration, to optimize the economic effect of the closed mine area development fund. The empirical output derived from this study would assist policymakers in establishing an effective distribution strategy for the closed mine area development fund in the future.

Effects of epigallocatechin gallate on CoCl_(2)-induced apoptosis in PC12 cells

Yang, Kyu-Ho,Mo, Hyun-Chul,Choi, Nam-Ki,Kim, Seon-Mi,Kim,Won-Jae 大韓小兒齒科學會 2006 大韓小兒齒科學會誌 Vol.33 No.1

Neuronal apoptotic events, consequently resulting in neuronal cell death, are occurred in hypoxic/ischemic condition. This cell death has been shown to be accompanied with the production of reactive oxygen species (ROS), which can attack cellular components such as nucleic acids, proteins and phospholipid. However, the underlying mechanisms of apoptosis induced in hypoxic/ischemic condition and its treatment methods are unsettled. Cobalt chloride (CoCl_(2)) has been known to mimic hypoxic condition including the production of ROS. Epigallocatechin gallate (EGCG). a green tea polyphenol, has diverse pharmacologial activities in cell growth and death. This study was aimed to investigate the apoptotic mechanism by CoCl_(2) and effects of EGCG on CoCl_(2)-induced apoptosis in PC12 cells. Administration of CoCl_(2) decreased cell survival in dose- and time-dependent manners and induced genomic DNA fragmentation. Treatment with 100 µM EGCG for 30 min before PC12 cells were exposed to 150 µM CoCl_(2), being resulted in the cell viability and DNA fragmentation being rescued. CoCl_(2) caused morphologic changes such as cell swelling and condensed nuclei, whereas EGCG attenuated morphologic changes by CoCl_(2). EGCG suppressed the apoptotic peak and a loss of Δψ_(m) induced by CoCl_(2). CoCl_(2) decreased Bcl-2 expression but Bax expression was not changed in CoCl_(2)-treated cells. EGCG attenuated the Bcl-2 underexpression by CoCl_(2). CoCl_(2) augumented the cytochrome c release from mitochondria into cytoplasm and increased caspase-8, -9 and caspase-3 activity, a marker of the apoptotic executing stage. EGCG ameliorated the incruement in caspase-8, -9 and -3 activity, and cytochrome c release by CoCl_(2). NAC (N-acetyl-cysteine), a scavenger of ROS, attenuated CoCl_(2)-induced apoptosis in consistent with those of EGCG. These results suggest, that CoCl_(2) induces apoptotic cell death through both mitochondria- and death receptor-dependent pathway and EGCG has neuroprotective effects against CoCl_(2)-induced apoptosis in PC12 cells. 신경세포자멸사는 저산소 및 허혈환경에서 일어나며 이러한 세포죽은 reactive oxidant species (ROS) 생성을 동반함이 알려져있다. 그러나, 저산소 및 허혈환경에서 일어나는 세포자멸사의 기전 및 그 치료방법은 아직 정립되어 있지 않다. CoCl_(2)는 ROS를 생성하는 등 저산소환경과 유사한 조건을 초래하는 것으로 알려져 있다. Epigallocatechin gallate (EGCG)는 녹차의 polyphenol 성분으로서 세포성장과 죽음에 다양한 약리학적 효과를 나타냄이 알려져 있다. 본 연구는 PC12 세포에서 CoCl_(2)에 의한 세포자멸사기전을 밝히고 이에 미치는 EGCG의 효과를 조사하는데 목적이 있다. Cell viability는 MTT 측정으로 조사되었고, DNA fragmentation은 DNA laddering으로 조사되었다. Bcl-2와 Bax발현 정도는 RT-PCR로, caspase-3와 -9의 활성은 spectrophotometer, caspase-8의 활성은 flow cytometry에 의해 측정되었다. 미토콘드리아에서 세포질로 분비된 cytochrome c는 western blot으로, 분해된 DNA 양과 미토콘드리아 세포막전위 (Δψ_(m))는 FACScan으로 조사되었다. CoCl_(2)투여로 PC12 세포수는 용량 및 시간 의존형태로 감소하였고, genomic DNA fragmentation이 발생하였다. CoCl_(2)투여로 야기된 cell viability의 감소와 DNA fragmentation은 EGCG 전처치에 의해 억제되었다. CoCl_(2)은 세포용적팽창과 condensed nuclei 같은 형태적 변화를 일으켰으며, apoptotic peak, Δψ_(m)감소 및 cytochrome c 유리를 야기하였다. EGCG는 CoCl_(2)에 의한 세포형태변화, apoptotic peak, Δψ_(m)소실 및 cytochrome c 유리를 억제시켰다. CoCl_(2)는 Bcl-2 발현을 감소시켰지만, Bax 발현에는 영향을 미치지 않았다. EGCG는 CoCl_(2)에 의해 야기된 Bcl-2 발현 감소를 억제시켰다. CoCl_(2)는 caspase-3, -8, 그리고 -9의 활성을 증가시켰으며, EGCG는 CoCl_(2)에 의한 세포자멸사를 억제시켰다. 본 실험결과는 PC12 세포에서 CoCl_(2)가 미토콘드리아 의존 및 death receptor의존 기전으로 세포자멸사를 일으키며, EGCG는 세포자멸사기전을 억세지킴으로 신경보호기능을 가짐을 시사하였다.

상수원수 수질변화에 따른 전오존 처리효과 및 경제성 평가

최동훈 ( Dong Hoon Choi ),박진식 ( Jin Sik Park ),문추연 ( Choo Yeun Moon ),이재용 ( Jae Yong Lee ),유동춘 ( Dong Choon Ryu ),장성호 ( Seong Ho Jang ),권기원 ( Ki Won Kwon ),이수애 ( Soo Ae Lee ) 한국환경과학회 2013 한국환경과학회지 Vol.22 No.4

This study, changes in raw water quality is to indicate on the efficiency of ozone treatment of each pollutant as compared to derive the appropriate operating measures. The appropriate selection for injection rate of pre-ozone and did not inject pre-ozone assess changes in the water. When good water quality, you not injected of pre-ozone to evaluate the economic efficiency of electricity and put the most cost-effective ozone concentration were evaluated. Evaluation remove organic matter and chlorophyll-a concentration level in experiments with each factor of the water DOC> 2.5㎎ / L, THMFP> 70㎍ / L, Chl-a> 30㎎/㎥or less constant process, if you do not need to put pre-ozone showed little impact. It also does not put you in pre-ozone appropriate produce enough power rate savings was calculated as approximately 90 million won. Ability to remove organic materials and the ability to produce disinfection byproducts, and cost-effective decisions by considering the concentration of injection if pre-ozone 1 mg/L was investigated by the appropriate concentration of ozone injection.

The Antioxidant Effect of the Rhaponticum uniflorum Extracts on the Oxidative Stress in H₂O₂ induced Human Keratinocytes

So Hee Ahn,Won Yeoung Choi,Ji Won Jeong,Geon Woo Park,Su Yeon Kang,Eun Jeong Kim,Su Rim Sin,Eun Seo Jang,Gye Won Lee,Young Ho Cho 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

In this study, To investigate the antioxidant activities of Rhaponticum uniflorum extracts (RUE), we assessed scavenging activities on DPPH, ABTS radicals, and reducing power. The DPPH and ABTS radical scavenging activities (SC50) of RUE were 96.97±1.19 μg/mL and 31.26±0.13 μ g/mL, respectively, and the reducing power significantly increased dose-dependent manner. To study the antioxidant effecters of RUE in H₂O₂ induced human keratinocytes, expression of Nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by Western blot and qRT-PCR. RUE induced the expression of HO-1, a critical target enzyme of Nrf2, in a concentration-dependent manner. The expression of HO- 1 mRNA was also induced in H₂O₂-treated HaCaT cells but no significant difference in the level of HO-1 mRNA was observed. Taken together, these results suggest that RUE may be useful as a potential ingredient for anti-aging products.

UV/Persulfate 산화 및 전기분해 방법을 이용한 TMAH 용액 및 부산물 처리 연구

최효연 ( Hyo-yeon Choi ),이용호 ( Yong-ho Lee ),이효주 ( Hyo-joo Lee ),이수민 ( Su-min Lee ),박대원 ( Dae-won Pak ) 한국폐기물자원순환학회(구 한국폐기물학회) 2019 한국폐기물자원순환학회 춘계학술발표논문집 Vol.2019 No.-

현재 TFT-LCD를 제조하는 과정에서 다양한 종류의 화학약품을 사용하며 이로 인해 다양한 종류의 폐수가 다량 발생되고 있다. 이 중 TMAH(Tetra methyl ammonium hydroxide)는 유입되는 질소의 주요 성분으로 TFT-LCD 제조 공정에 있어서 핵심 공정 중의 하나인 Photo 공정 중 포토 레지스트(photo resist)의 현상액으로 사용되는 강알칼리의 유기 아민계 용액으로, 무색, 투명의 강염기성 물질이고, 수용성, 가연성의 성질을 나타낸다. 또한 그 농도가 증가하면서 강한 독성을 배출하여 생물학적 분해가 어렵고, 분자 구조 속에 질소를 포함하고 있어, 분해 시 암모니아성 질소를 생성하는 특성을 가지고 있다. 이에 따라 자연 수중 생태계에 영향 등의 문제가 발생되기 때문에 TMAH 폐수의 효율적인 처리방법 도출이 필요한 사항이다. 현재 TMAH를 함유한 폐수는 호기성 생분해, 혐기성 생분해, 촉매 산화, 광촉매 분해(UV 조사) 또는 이온 교환 기술 등으로 처리되고 있습니다. 그 중 UV 조사는 과황산염 활성화를 위한 에너지의 한 형태로 적용되며 난분해성 분해에 많이 적용되고 있다. 과황산음이온(S₂O₈ ^2-)은 산화환원전위가 2.01 V인 강한 산화제이며 토양과 지하수에 존재하는 유기오염물질을 분해하는데 효과적이라고 한다. 과황산염 반응 메커니즘은 다양한 과황산염 활성화를 통한 강한 황산염 라디칼(SO₄^-·) 및 하이드록실 라디칼(HO^·)의 생성에 기반을 두고 있으며 1 mole의 황산염은 자외선 조사를 통해 2 mole의 황산염 라디칼을 생성하도록 활성화 될 수 있다고 보고되어 다양한 난분해성 유기 오염 물질을 분해에 적용되고 있다. 전기화학적 산화 처리공정은 고분자량을 가지는 화합물을 파괴하며 난분해성 유기물질의 독성을 감소시킬 수 있어 효과적인 것으로 제시되고 있으며, 고도처리공정들 가운데 오염물질 생분해성과 관계없이 높은 제거율과 처리시간이 짧은 운전특성을 나타내고 있어 유기화합물 또는 질소화합물의 제거에 있어서 응용가능성이 높은 것으로 평가되고 있다. 따라서, 본 연구에서는 TMAH 모형폐수를 제조하여 먼저 과황산염(S₂O₈ ^2-)을 이용한 UV 산화방법으로 TMAH를 분해하고 그에 따른 부산물을 전기분해 방법으로 처리하고자 하였다.

키넥트 센서를 이용한 고령자 대상의 선자세 균형능력 평가

양승태(Seung-Tae Yang),강동원(Dong-Won Kang),서정우(Jeong-Woo Seo),김대혁(Dae-Hyeok Kim),김태호(Tae-Ho Kim),최진승(Jin-Seung Choi),탁계래(Gye-Rae Tack) 대한전기학회 2017 전기학회논문지 Vol.66 No.2

Portable low-cost Kinect sensor was used to analyze standing balance ability of the elderly. Eighty subjects who can walk alone and have a normal cognitive level participated in this experiment. Based on Berg Balance scale (BBS) test with 52 points, subjects were divided into Healthy older (HO: 46 persons, BBS: 53.80 ± 1.19) and Impaired older (IO: 34 persons, BBS: 49.06 ± 2.03) group. Each subject performed 30 seconds four different standing balance tests (EO: Eyes Open, EC: Eyes Close, EOf: Eyes Open on foam, ECf: Eyes Close on foam). Five variables (Mean distance, Range of distance, Root mean square, Mean velocity, 95% ellipse area) were calculated from the hip joint center movement of Kinect sensor. Results showed that there were significant differences between groups for four different standing tests. Calculated variables from kinect sensor showed significant correlation with BBS score. Especially, mediolateral mean distance, mediolateral root mean square, mediolateral range of distance and 95% ellipse area showed discriminative ability for all tests. Mean values of variables of IO were higher than those of HO, which means the decreased balance ability in IO compared with HO. Therefore, it was possible to estimate simple balance assessment of the elderly using portable low-cost Kinect sensor.

Omeprazole 투여시 위산분비 억제능에 대한 CYP2C19 의 영향

박수헌(Soo Heon Park),김종원(Jong Won Kim),이수연(Soo Youn Lee),최명규(Myung Gyu Choi),김재광(Jae Kwang Kim),정인식(In Sik Chung),정규원(Gyu Won Chung),선희식(Hee Sik Sun),박두호(Doo Ho Park) 대한소화기학회 2001 대한소화기학회지 Vol.38 No.6

Background/Aims: CYP2C19 has an important role in the catabolism of several proton pump inhibitors. However, the relative contribution of CYP2C19-mediated metabolism varies among the different proton pump inhibitors. We investigate to determine the effect of CYP2C19 genotype status on intragastric pH during dosing with omeprazole. Methods: The subjects were 16 healthy volunteers. Their CYP2C19 genotype status was determined by a polymerase chain reaction-restriction fragment length polymorphism method. Twenty-four-hour monitoring of intragastric acidity were performed on the day without medication and day 4 after omeprazole administration. Results: A single dose of omeprazole significantly decreased 24 hour intragastric acidity (1.7±0.3 vs. 5.1±0.4). Subjects were divided into three groups on the basis of their CYP2C19 genotype status: homozygous extensive metabolizers (Ho-EMs, n=5), heterozygous extensive metabolizers (Ht-EMs, n=6), and poor metabolizers (PMs, n=5). Median 24 hour intragastric pH in the Ho-EM group was 3.1 compared with 5.5 in Ht-EM group and 5.9 in PM group(P<0.05). The median pH during omeprazole administration was influenced by CYP2C19 genotype. On the other hand, the Helicobacter pylori infection did not influence the median intragastric pH during omeprazole administration (p= NS). Conclusions: The effects of omeprazole on intragastric acidity is influenced by the CYP2C19 polymorphism. (Korean J Gastroenterol 2001;38:399-404)

신규 방사성 항암제 DW-166HC 의 소핵시험

문은이(Eun Yi Moon),이진(Jin Lee),이원용(Won Yong Lee),최청하(Chung Ha Choi),이덕근(Dug Keun Lee),유제만(Jei Man Ryu),정용호(Yong Ho Chung),윤성준(Sung June Yoon),박경배(Kyung Bae Park) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3

DW-166HC (^(166)Holmium (^(166)Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumorigenic spectrum, especially against human hepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous arid intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I (^(165)Ho-Chitosan complex : cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC (^(166)Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr arid 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative controi group but there was significant difference of this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.