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]

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>

Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

조혈모세포이식술이 골수기질세포의 기원 및 조골세포로의 증식 및 분화에 미치는 효과

강무일,조성원,오은숙,백기현,이원영,오기원,김혜수,한제호,윤건호,차봉연,이광우,손호영,강성구,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

재한줌머공동체의 ‘실금’과 한국사회의 다문화 수용력

유승무(Ryu, Seung-Moo),신종화(Shin, Jong-Hwa),박종일(Park Jong-il),이태정(Lee, Tae-Jeong),박수호(Park, Su-Ho) 고려대학교 아세아문제연구소 2013 亞細亞硏究 Vol.56 No.1

The purpose of this paper is to highlight, with the help of the Jumma community, a refugee community in Korea, the way in which the immigrant community is affected by the combination of the two factors, the adaptibility of the immigrants and the receptibility of Korean society. The main argument is to identify the fact that the components of the pre-state identities, which detonates the refugeefication, lead the internal differentiation of the refugee community due to the refugee’s strategy of adaptation, on the one hadn, and the characteristics of supporting organizations of the protection states, on the other. In this paper, first, the special aspects of refugees in their development are investigated, and, second, the Jumma community’s effort to keep their pre-state identities and the formative process of the Jumma community in Korea are evaluated. Thu authors identify the phenomenon of differentiation among refugees through the relationship with the supporting organizations in Korea. This division process of the refugee community possibly accelerates the dissolution and break-up of immigrant community. For this reason, the systematic management of refugees is also required. The outcome of this research includes: first, the immigrant community, which has been assumed as the united and homogeneous community, is internally evolved to different directions; second, the evolution of the immigrant community is led or strengthened by the supporting organizations in Korea which is relate to their own interests; third, the research on refugees, which has been alienated in the immigration and multiculturalsim studies for a long time, is evoked loudly; the importance of religion for the refugees’ adaptation process to the protecting country; last but not least, the Korean society is asked for its multicultural receptive policies to respect the tradition of the immigrant community and to manage their internal differentiation.

골수이식 후 골밀도 및 골대사의 변화 : 2년 추적관찰 2-Year Prospective Study

이원영,강무일,오은숙,오기원,한제호,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

Gliotoxin ameliorates TNBS-induced colitis through regulation of NF-kB, and up-regulation of HO-1

김상욱 ( Kim Sang Ug ),( Jay Min Oh ),( Yeon Hwa Kim ),( Jung Moo Hur ),( Kyo Sang Yoo ),( Yong Sung Kim ),( Joo Jin Yeom ),( Tae Hyeon Kim ),( Suck Chei Choi ),( Chang Duk Jun ),( Yong Ho Nah ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-

<Background & aims> During inflammation in colon, cells of the gut mucosa produce or express various inflammatory mediators, including IL-8, TNF-a and IL-1b, and intercellular adhesion molecule 1 (ICAM-1). These cytokines and chemokines have recently been

무연(無緣) 사회 현상의 사회학적 이해

유승무(Lew, Seung-Moo),박수호(Park, Su-Ho),신종화(Shin, Jong-Hwa),이민정(Lee, Min-Jung) 한국이론사회학회 2015 사회와 이론 Vol.27 No.-

이 논문은 최근 한국 사회에서 점차사회문제로 부상하고 있는 무연 사회 현상을새로운 관점에서 이해하기 위한 이론적프레임의 모색을시도하였다. 이러한 문제의식의 기저에는 일본 NHK가 무관계 사회 혹은 무연고 사회로 정의한 ‘무연 사회’라는 개념이 사회학적 맥락에서 성립 불가능한 모순된 개념임에도 불구하고 무비판적으로 사용되고 있다는 인식과 고령화나 가족 및 공동체의 해체 등을 무연 사회의 원인으로 규정하는 선행 연구들의 피상성을 극복해야 할 필요성이 자리하고 있었다. 이와 같은 문제의식을 해결하는 과정은 무연 사회 현상의 바탕에 마음의 멀어짐과 닫힘이 있음을 확인하는 것에서부터 출발하였다. 2000년 이후 14년 동안 주요 4개 일간지에 사용된 단어들의 활용 빈도와 그들 사이의 상관성을 통해 사회적 관계로서 의연(緣) 현상이 마음과 일정한 상관관계를 가지고 있으며, 연줄과 절연 및 무연고라는 단어의 사용이 정적인 관계를 보이고 있음도 확인하였다. 그리고 절연과 무연 사회 현상에는 갈등이나 트라우마 같은 마음고생의 계기가 존재하며, 관계 회복을 위한 의지와 마음의 강도에 따라 절연 상태의 유지 여부가 달라질 수 있음을 구체적 사례들을 통해 알 수 있었다. 이상의 사실들을 통해 ‘연’이라는 사회적 현상이 구체적 사회관계의 잠재성으로서 ‘포함과 배제의 상즉상입 과정’과 ‘관심과 무관심의 상즉상입’이라는 마음의 매개과정이 일정한 방식으로 결합함으로써 친근과 소원이라는 두 가지 유형의 관계로 발현하며, 대인관계와 집단관계라는 관계적 차원에 따라 모두 네 가지의 ‘연’ 유형이 나타남을 모델화하였다. 그리고 내재적, 외재적요인에 의해 촉발된 갈등상황이 축적됨으로써 발생한 마음의 실금이 관계 회복을 위한 노력의 정도에따라 우호적 관계를 복원하거나 절연상태로 전개되며, 다양한 관계에서 절연 현상이 중첩적으로 나타날때 무연 사회 현상이 나타남을 도식화할 수 있었다. 마지막으로 이 논문의 연구결과는 마음을 사회적 배제의 요인으로 도입해 사회적 배제 이론의 지평을 확장하고, ‘마음의 사회학’을 발전시키는 데 기여하고, 사회관계의 회복을 통해 무연 사회 현상의 예방 및 무연 상태의 사회적 약자들이 사회에 기여할 수 있는 방안을 모색하는 계기가 될것으로 기대한다. This paper aims at building a theoretical framework for newly understanding so-called ‘no-relationship’ society, which is emerging as a social problem in the Korean society recently. This purpose is based on the necessity of overcoming superficiality of the term, ‘no-relationship’ society from a Japanese broadcasting company, NHK, on the one hand, and of the previous literature which poins out aging society or the fragmentation of family and community as the main cause of rising ‘no-relationship’ society, on the other. Authors get this study started where there is a social fact that one’s heart(마음, 心) is distantiated from a relation with the others and closed finally, under the phenomenon of ‘no-relationship’ society. Authors also identify, with a longitudinal study of daily newspaper on the text mining technique, that the phenomenon of Yeon(연, 緣) as the social relation in the to some extent correlation with heart, at first, relational line(연줄, yeon-jool), cutting relation(절연, 切緣, jeol-yeon), and no-relationalbackground(무연고, 無緣古, moo-yeon-goh), these three words show positive relations each other in the correlation test of a statistical approach, at second. By the way, authors recognize that there are motives of psychological heart troubles, for example conflict, trauma, in the phenomenon of cutting relation and no-relationship society, on the one hand, and whether the state of cutted-relation is maintained or not, namely relationship is restored, is dependent on the strength of will and heart for reviving relations. Authors build two research models: the first one shows that two types of relations, closenss and estrangement are developed as a combinational consequence of ‘the mutual process of inclusion and exclusion’ and ‘the mutual penetration and wayout of concern and indifference’. The second one has four type of ‘relation(yeon)’ on the relational dimension of individual and group relations. Besides, draw a picture that no-relationship society appears when the cutting-relation phenomena in several relations are overlapped. There are two ways: the state of cutted-relation and the restoration of friendship. These are the result of effort to revive relations overcoming micro fragmentation of heart occurred by the accumulation of conflict caused by internal and external factors. Authors expect with the paper that the theory of social exclusion and the sociology of heart are connected by the way of introducing ‘heart’ as the factor of social exclusion and it would promote to find solutions for social minorities in the state of no-relationship and prevent them from other phenomena of no-relationship society through the restoration of social relations.

Mirizzi 증후군의 변형된 분류와 치료

김형철,강길호,채만규,김성용,백무준,이문수,박상흠,이문호,김창호,송옥평,조무식,박희주 순천향의학연구소;Soonchunhyang Medical Research Institute 2000 Journal of Soonchunhyang Medical Science Vol.6 No.1

Purpose : The Mirizzi syndrome is relatively rare and preoperative diagnosis of this disease is difficult. In 1978, Morelli suggested the subclassification of the Mirizzi syndrome into acute or chronic form. We experienced 5 cases of acute form. We analysed clinical features, preoperative radiologic findings and operative findings of 18 cases including acute forms which were diagnosed as Mirizzi syndrome and should suggest the modified classification of Mirizzi syndrome for choice of appropriate treatment. Method : From January 1995 to December 1998, 18 cases, of which 8 cases were diagnosed at Soonchunhyang University Chunan Hospital, and 10 cases were reported in the Korean Journal were retrospectively analysed with regard to clinical features, preoperative radiologic findings and operative findings. According to the clinical features, whole cases were divided into type Ⅰ(acute form) and type Ⅱ(chronic form) and then each type of cases were subclassified according to preoperative radiologic findings and operative findings. Results : Of 18 cases there were 5 cases in type Ⅰ(27.8%), 13 cases in type Ⅱ(72.2%). Type Ⅱb was most common. Type Ⅰa cases were treated only with cholecystectomy. We applied cholecystectomy, T-tube choledochostomy and patch technique in type Ⅰb and thpe Ⅰc cases. Cholectystectomies including removal of gallstones and internal drainage procedures were done in type Ⅱ chronic forms. Conclusion : The acute form(Type Ⅰ) of Mirizzi syndrome was suggested by Morelli might be subclassified into typeⅠa,Ⅰb and Ⅰc following the presence of the necrotic defect in common hepatic duct. Through the modified classification of Mirizzi syndrome based on clinical feature, preoperative radiologic findings and operative findings, we can choice appropriate treatment.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Tae Kyeong Shin,Mi Sun Kang,Ho Youn Lee,Moo Sang Seo,Si Geun Kim,Chi Dae Kim,Won Suk Lee 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1Ձ (HIF-1Ձ) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1Ձ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.