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]

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>

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.

Ho-166 부착풍선도자를 이용한 방사선 조사의 돼지 관상동맥 스텐트 재협착 예방 효과

김원 ( Kim Won ),정명호 ( Jeong Myeong Ho ),박옥영 ( Park Og Yeong ),정우곤 ( Jeong U Gon ),박우석 ( Park U Seog ),김주한 ( Kim Ju Han ),안영근 ( An Yeong Geun ),조정관 ( Jo Jeong Gwan ),박종춘 ( Park Jong Chun ),강정채 ( Kang Je 한국지질동맥경화학회 ( 구 한국지질학회 ) 2002 韓國脂質學會誌 Vol.12 No.1

배경 : 국내에서 개발된 방사선 동위원소 Holmium-166 (166Ho)은 주로 베타선을 방출하며, 166Ho을 부착한 풍선도자를 이용하여 돼지 관상동맥 재협착 모형에서 풍선확장술 후 신생내막 증식을 전신적 부작용 없이 안전하고 효과적으로 억제하였음을 보고한 바 있다. 본 연구에서는 돼지 관상동맥 스텐트 재협착 모형에서 스텐트 시술 후 신생내막 증식에 의한 재협착 병변을 166Ho 부착 풍선도자를 이용하여 치료하여 그 효과를 관찰하고자 하였다. 방법

Comparison of the community structure and changes of ground beetle (Coleoptera: Carabidae) as indicator species in forest genetic resource reserve

Myeong–Ho Kim,Min-Chul Kim,Seung-Gyu Lee,Il-Kwon Kim 한국응용곤충학회 2018 한국응용곤충학회 학술대회논문집 Vol.2018 No.04

2016년도에 조사를 수행한 경상북도 내 위치한 산림유전자원보호구역 3개 지역(봉화・영주・울진)의 곤충 군집 변화를 확인하기 위하여 5월에서 9월까지 함정 트랩(pitfall trap)을 이용하여 5회씩 3반복하여 각각 상대적으로 비교 하였다. 채집된 딱정벌레류는 딱정벌레과 등 22과 141종 2,415개체가 확인 되었으며, MRPP (Multi-response Permutation procedures)분석 결과 서식지간의 군집구조차이가 있음을 확인 하였고(p < 0.001), Bray-cutis 분석결과 군집간의 차이와 함께 신갈나무 군락이 보행성 딱정벌레류의 종 풍부도에 큰 영향을 주는 것으로 나타났고 소나무군락 은 비교적 낮은 영향을 받았다. 식생유형에 대한 지표종 분석결과 신갈나무 군락에서 붉은칠납작먼지벌레(Synuchus cycloderus Bates, 1873)를 포함한 4종, 자작나무 군락에서는 노랑털검정반날개(Ocypus weisei Harold, 1877)를 포함한 3종, 소나무 군락에서는 홍딱지반날개(Platydracus brevicornis Motschulsky, 1862)를 포함한 3종의 지표종 변화를 확인 하였다.

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

Yun Ho Jo,Hwan Lee,Myeong Hwan Oh,Gyeong Hee Lee,You Jin Lee,Ji Sun Lee,Min Jung Kim,Won Yong Kim,Jin Seong Kim,Dae Seok Yoo,Sang Won Cho,Seon Woo Cha,Mi Kyung Pyo 한국영양학회 2020 Nutrition Research and Practice Vol.14 No.4

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson"s trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

품질경영에 대한 지식창출 요인에 관한 탐색적 연구

김경호,김명숙 김천과학대학 2002 김천과학대학 논문집 Vol.28 No.-

Many companies have own ways of Quality improvement. This is shown that all activities of Quality Management are part of Knowledge Management. Therefore, to find Knowledge Creation Factors is a preliminary step for firms to do better Quality Management. This study focuses primarily on finding Knowledge Creation Factors among Quality Award items.

수종 근관확대 기구의 만곡된 치근관 성형능력

김명수,손호현 大韓齒科保存學會 1992 Restorative Dentistry & Endodontics Vol.17 No.1

우리나라 住宅金融制度의 問題點과 改善方案에 관한 硏究

金明浩 청주대학교 대학원 1994 우암논총 Vol.11 No.-

Housing Finance, a special kind of finance, is differentiated from others in respect of raising funds, lending, and management. The housing financial system has to be a support for settled housing so that raising funds for purchasing a house can be achieved well and so that supply and demend for houses can be balanced. Firstly, I shall explain the speciality of housing finance in general terms and the method of activating housing finance for the stability of residence of the people and the improvement of the level of housing of the people. Secondly, we must look below the affluent classes and control projects supported by national housing funds so that the middle class and upper class cannot be included in projects which are supported by funds raised politically. Thirdly, in order to ensure fund-raising methods, we have to increase housing finance quantitatively. Fourthly, we must establish a Refinancing Organization for floating mortgage loan bonds. Fifthly, if raising funds for housing is to be well achieved, we must put an end to the forced absorption system of national housing bonds and the housing lottery system. Sixthly, we must ensure that priority is given to policies which guarantee high interest rates on general housing funds, which come from housing deposit and national housing application savings. These improvement methods, as stated above, have no achievements in the short term, but must be executed as urgent national policies in view of the social and economic improtance of housing. In conclusion, the paramount take to develop the housing finance is that the Government recognize that the housing is the most significant public good for the nation's welfare. And we should promote the housing industry through extension of the Government's financial investment in the housing sector.