Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

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>

Korean Red ginseng prevents endothelial senescence by downregulating the HO-1/NF-κB/miRNA-155-5p/eNOS pathway

Tae-Hoon Kim,Ji-Yoon Kim,Jieun Bae,Young-Mi Kim,Moo-Ho Won,Kwon-Soo Ha,Young-Guen Kwon,Young-Myeong Kim 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.2

Background: Korean Red ginseng extract (KRGE) has beneficial effects on the cardiovascular system by improving endothelial cell function. However, its pharmacological effect on endothelial cell senescence has not been clearly elucidated. Therefore, we examined the effect and molecular mechanism of KRGE on the senescence of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were grown in normal or KRGE-supplemented medium. Furthermore, they were transfected with heme oxygenase-1 (HO-1) gene or treated with its inhibitor, a NF-κB inhibitor, and a miR-155-5p mimic or inhibitor. Senescence-associated characteristics of endothelial cells were determined by biochemical and immunohistochemical analyses. Results: Treatment of HUVECs with KRGE resulted in delayed onset and progression of senescence-associated characteristics, such as increased lysosomal acidic β-galactosidase and decreased telomerase activity, angiogenic dysfunction, and abnormal cell morphology. KRGE preserved the levels of anti-senescent factors, such as eNOS-derived NO, MnSOD, and cyclins D and A: however, it decreased the levels of senescence-promoting factors, such as ROS, activated NF-κB, endothelial cell inflammation, and p21 expression. The beneficial effects of KRGE were due to the induction of HO-1 and the inhibition of NF-κB-dependent biogenesis of miR-155-5p that led to the downregulation of eNOS. Moreover, treatment with inhibitors of HO-1, NF-κB, and miR-155-5p abolished the anti-senescence effects of KRGE. Conclusion: KRGE delayed or prevented HUVEC senescence through a signaling cascade involving the induction of HO-1, the inhibition of NF-κB-dependent miR-155-5p biogenesis, and the maintenance of the eNOS/NO axis activity, suggesting that it may protect against vascular diseases associated with endothelial senescence.

임상 증상이 심하지 않은 심낭 삼출 환자의 장기 추적 결과

배장호,김기식,강미숙,남명희,김미정,김민수,김기영,님창욱,김윤년,김권배,정시전,김여희 대한순환기학회 1999 Korean Circulation Journal Vol.29 No.7

Study of decreased melanin production through p53 by heme oxygenase-1 inhibitor in normal human melanocytes

( Hee Sun Lim ),( Sun A Jin ),( Jee Bum Lee ),( Seong Jin Kim ),( Seung Chul Lee ),( Young Ho Won ),( Sook Jung Yoon ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Heme oxygenase (HO)-1 is induced by oxidative stress and plays important roles in anti-apoptosis and the rapid growth of several solid tumors. p53 has a central role in skin pigmentation and may impact onmelanoma at all stages. However, there has been little study of HO-1 in relation with p53 on melanin production Objectives: To know the effect of HO-1 on melanogenesis through p53 in normal human melanocytes Methods: Human melanocytes (hM) were primarily cultured from foreskin. After incubation, cells were rinsed twice with PBS then transfection with p53 siRNA Results: Melanin content was detected with ELISA and Western blot analysis and RT-PCR of tyrosinase, MITF were performed after ZnPP treatment and p53 transfection. After ZnPP treatment, melanin content was decreased, and tyrosinase and MITF protein levels were decreased. Tyrosinase and MITF mRNA levels were also decreased. However, melanin content and tyrosinase and MITF protein levels were increased after CoPP treatment. After p53 transfection, HO-1 expression was decreased when HO-1 stimulator was treated. In addition, melanin content was decreased, and tyrosinase expression was decreased in Western blot analysis Conclusion: These results suggest that melanogenesis is inhibited by ZnPP by decreased melanin production, tyrosinase and MITF protein and mRNA levels. Furthermore, those inhibitory effects of ZnPP may be dependent on p53 in normal human melanocytes. Therefore, HO-1 may play an important role in melanogensis

유휴 산업시설을 활용한 국내 전시관의 재생사례 연구

김인호 ( In Ho Kim ),윤재은(교신저자,교수) ( Jae Eun Yoon ) 한국공간디자인학회 2016 한국공간디자인학회논문집 Vol.11 No.3

(연구배경 및 목적) 산업구조가 변화하면서 자연스럽게 유휴 산업시설이 생겨났고, 유휴 산업시설을 활용해 다양한 전시관 및 문화공간들이 생겨났다. 그것이 도시 재생으로 이어지고 지역경제 활성화로 이어지고 있는 것이 세계적인 추세다. 이러한 시대적 흐름에 맞추어 국내에서도 유휴 산업시설의 재생이 활발히 진행되고 있으며, 유휴 산업시설을 활용한 다양한 사례의 전시관들이 있다. 따라서 본 연구는 유휴 산업시설을 활용한 국내 전시관 사례분석을 통해 필요한 구성요소를 알아보고 앞으로 유휴 산업시설을 활용하는데 있어 기초자료를 마련하는데 목적이 있다. (연구방법) 본 연구에서는 유휴 산업시설 재생에 대한 개념과 특성 그리고 문화공간으로서의 가치에 대한 이론을 고찰하였다. 국내 사례 분석에 앞서 성공적인 해외사례지 바탕으로 한 선행논문분석을 통해 정체, 보존, 사회, 환경을 카테고리를 도출하였다. 또한 국내 사례지를 바탕으로 한 선행논문 분석을 통해 역사성, 상징성, 구조체보존, 재료보존, 참여성, 연계성, 접근성, 장소성 총 여덟 가지 키워드를 도출하였다. 앞서 나온 해외사례를 중심으로 한 논문분석에서 나온 네 가지 카테고리와 국내사례를 중심으로 한 논문분석에서 나온 여덟 가지의 키워드를 재정리하여 국내사례를 분석하고자 한다. 사례지를 선정한 기준은 지역재생 활성화의 거점의 공간으로 전시관으로 리노베이션이 되고, 지역적 특색이 명확하게 나타난 곳으로 분석의 대상으로서 유효한 가치가 있는 장소들이다. 이에 합당한 사례지는 정선 삼탄아트마인, 윤동주 문학관, 김중업 박물관, 광명 업사이클 아트센터, 인천 아트 플랫폼으로 다섯 곳으로 선정하였다. 앞서 추출한 각 4가지 분류와 총 8가지의 키워드로 분석의 틀을 설정하고 문헌연구와 현장조사를 통하여 국내의 유휴 산업시설을 활용한 전시관사례를 분석 하고자 한다. (결과) 이를 기반으로 정선 삼탄아트마인, 윤동주 문학관, 김중업 박물관, 광명 업사이클 아트센터, 인천 아트 플랫폼을 분석한 결과 정선 삼탄아트마인은 정체성과 보존도가 높은 것으로 나타났다. 윤동주 문학관에서는 전체적인보존 에서 재료 보존도를 제외하고 골고루 높은 것으로 보였고, 김중업 박물관에서는 사회분야와 환경분야 요소들이 집중적으로 높은 것으로 나타났다. 광명 업사이클 아트센터에서는 사회분야에서 참여성과 연계성이 높은 것으로 나타났고, 인천 아트 플랫폼 에서는 사회분야에서는 연계성, 환경 분야에서는 두 가지 요소 모두 높은 것으로 나왔다. (결론) 이에 본 연구에서는 유휴 산업시설이 활용되는 전시관에서는 정체성은 보존도와 서로 연관이 있고, 환경 분야는 사회분야와 서로 영향을 주는 밀접한 관계가 있는 것으로 분석되었다. 보존도가 높은 전시관에서는 역사성 그 자체가 전시의 요소로 활용 되고 있다. 이러한 요소가 전시관의 강한 정체성을 구성하며 이로 인해 관람자가 이전에 쓰였던 공간의 역사와 상징을 알 수 있고 그것이 전시관을 구성하는 정체성을 이루는 것을 알 수 있었다. 또한, 지방자치단체의 사회적 연계성과 지리적의 접근의 용이함이 지역적 활성화를 이끌어 내는 것으로 나타났다. 이는 도시재생을 위한 기틀이 되고 있음을 알 수 있었다. (Background and Purpose) The reason why industrial structure is changing, arrived so many idle industrial facilities were created. This social phenomena makes to use idle industrial facilities as the Museum or cultural space. And then this kinds of idle industrial facilities can carry over Urban Renaissance and regional economic vitalization. Nowadays, South Korea also Recovery and change idle industrial facilities to play actively, besides, already many cases of culture spaces used to idle industrial facilities in Korea. Therefore, in this research, through the national pavilion of the case analysis utilizing idle industrial facilities, examine the necessary components in order to take advantage of the idle industrial facilities, there is a purpose to prepare the future of basic data. (Method) In this study, we consider the theory of value as a concept and characteristics and cultural space for the idle industrial facilities of playback. Before analyze Korean cases, we’d analyze international cases to got four categories, that is identity, conservativeness, society, environment. also we’d extract the keyword from previous research about the idle industrial facilities of playback. That keyword is historicity, symbolism, conservation structures, preservation material, community attribute, connectivity, placeless. We’ve use that analyzed four categories and eight keyword, to analyze South Korea’s cases. This chose areas are systematically related to municipality or renovated space. The identity-clear place that has regional characteristics also can be a chosen case areas. The chosen case areas are space that is valued as a subject of analysis. These five case areas Jeongseon Samtanartmine, Yoon-dong-ju literary house, Kim-jung-up museum, Gwangmyeong epicycle art center, Incheon art platform will be researched. Now, we begin to analyze gallery characteristics with 8 keyword that broken down from precede thesis’ four classifications. (Result) Through the study, we can know that Samtanartmine has the best condition of identity and preservation. Yoon-dong-ju literary house have a good balance except preservation of materials. Kim-jung-up museum have social and environmental factors intensively. Gwangmyeong upicycle art center have good at social connectivity and community attribute, Incheon Art platform have high quality at social connectivity and environment. (Conclusion) Therefore, in this study, in the exhibition hall of idle industrial facilities have been utilized, identity, are related to each other and the field of preservation, the environment, that there is a close relationship that gives society in the field and each other to the impact It was analyzed. In the highly conserved Exhibition Hall, the historic property itself has been used as an element of the exhibition. These elements constitute a strong identity of exhibition hall, by which, onlookers can know the history a symbol of previously used space, it was found that forming the identity constituting the pavilion . Also, ease of social cooperation with geographic access local governments has been found to result in activation of the region. This was found to be the basis for urban regeneration.

Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

Lee, Yoo-hwan,Kim, Jung-hee,Song, Choon-ho,Jang, Kyung-jeon,kim, Cheol-hong,Kang, Ji-Sook,Choi, Yung-hyun,Yoon, Hyun-Min KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.1

Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, $H_2O_2$) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and $H_2O_2$ in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and $H_2O_2$-induced growth inhibition. Results: The results showed that EGL effectively inhibited $H_2O_2$-induced growth and the generation of ROS. EGL markedly suppressed $H_2O_2$-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 ($p-{\gamma}H2AX$), a widely used marker of DNA damage, suggesting that EGL prevented $H_2O_2$-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against $H_2O_2$-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from $H_2O_2$-induced oxidative cytotoxicity.

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

ORiginal Article : Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

( Yoon Jeong Choi ),( Nayoung Kim ),( Ju Yup Lee ),( Ryoung Hee Nam ),( Ji Hyung Seo ),( Seonmin Lee ),( Hee Jin Kim ),( Yoon Jin Choi ),( Hye Seung Lee ),( Dong Ho Lee ) 대한간학회 2016 Gut and Liver Vol.10 No.3

Background/Aims: This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-Lcysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. Methods: Sprague- Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanolonly group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor a, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. Results: PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMKS005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. Conclusions: These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes. (Gut Liver 2016;10:348- 355)