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]

경량골재 콘크리트에 현무암의 재활용 방안연구

정영화,이정호,윤경구,윤청호 강원대학교 석재복합신소재제품연구센터 1997 석재연 논문집 Vol.2 No.-

현무암을 콘크리트 골재로 이용하여, 환경오염 방지와 에너지 절감 효과를 얻을 수 있다. 반요인실험법을 사용하여 현무암을 굵은골재에 일정한 비율로 치환한 콘크리트의 최적배합설계 제시를 위한 예비 실험에서 현무암의 굵은골재 치환율, 물-시멘트비, 잔골재율, 슬럼프와 같은 주요 변수와 변수 사이의 2차 상관관계를 파악하였다. 예비실험을 한 결과 현무암을 굵은골재로 100%까지 치환했을 때 현무암을 혼입한 콘크리트의 강도 발현에 가장 중요한 변수는 물-시멘트비로 분석되었고, 현무암의 굵은골재 치환율은 강도 발현에 거의 영향이 없는 것으로 분석되어 현무암을 콘크리트의 굵은골재로 대체할 수 있다는 것을 알게 되었다. 변수 사이의 2차 상관관계에서는 현무암의 굵은골재 치환율과 잔골재율의 상관관계가 콘크리트의 강도 발현에 가장 큰 영향을 미치는 것으로 나타났다. 목표압축강도를 만족하는 현무암을 혼입한 콘크리트의 최적배합설계는 현무암의 굵은골재 치환율, 물-시멘트비, 잔골재율에 관하여 제시하였다. The waste basalt might be used in concrete aggregate, saving energy and protecting environment. An half-factorial experiments were performed with the primarary variable such as water-cement ratio, waste basalt substitution ratio, fine aggregate ratio and slump as a preliminary study for optimum mix design of concrete. The preliminary study show that the water-cement ratio is the most important factor to the concrete strength, followed by slump. The substitute of waste basalt up to 70% has little infulence, indicating that it can substitute the coarse aggregate without damaging the Concrete strength. The interaction between waste basalt substitution ratio and fine aggregate ratio was most significant to the concrete strength among the 2-way interaction variable. Only compressive strength affect to the formation of optimum mix design area as target compressive strengh becomes bigger. Optimum mix designs of concrete incorporating waste basalt, satisfying the target responses, were proposed in terms of waste basalt substitution ratio, water-cement ratio and fine aggregate ratio.

급성전골수성백혈병에서 백혈구성분채집술에 이은 치명적인 뇌출혈 2예

오윤정,박소윤,김윤정,한동석,김현수,최진혁,남동기,임호영,김효철,주희재 아주대학교 의과학연구소 1998 아주의학 Vol.3 No.1

The aim of this study is to report 2 cases of acute promyelocytic leukemia who died from intracranial hemorrhage following leukapheresis and to provide proper preventive measures against hemorrhage following leukapheresis. From 1994 to 1997, a total of twenty-six patients with leukemia underwent leukapheresis to control hyperleukocytosis at Ajou University Hospital. Two patients with acute promyelocytic leukemia received all-trans retinoic acid but developed drug-induced hyperleukocytosis. Shortly after leukapheresis, they died from intracranial hemorrhage. The risk factors for fatal hemorrhage are thought to be coexisting disseminated intravascular coagulation(DIC), thrombocytopenia aggravated by leukapheresis, exacerbated coagulopathy related to mechanical trauma through leukapheresis and the excess use of citrate during leukapheresis. To reduce the risk of the bleeding associated with leukapheresis, it is necessary to replace platelet sufficiently before and after leukapheresis and to give calcium to correct coagulopathy induced by excess citrate which is used as anticoagulant as well as the correction of disseminated intravascular coagulation.

권역단위 농촌지역개발사업의 주민역량 측정을 위한 설문도구개발

리신호 ( Shin Ho Rhee ),민흥기 ( Heung Gi Min ),윤성수 ( Sung Soo Yoon ),정남수 ( Nam Su Jung ),장우석 ( Woo Seok Chang ) 한국농촌계획학회 2014 농촌계획 Vol.20 No.4

The purpose of this study was to develop survey tools for diagnosis of capacity levels in business promotion of rural residents when performing a rural development project of a regional unit. The cases of previous studies were analyzed to select community capacity indicators related to a rural development project. Five indicators were derived : social capital, consciousness of participation, community spirit, and leadership. Based on the five indicators, measurement items of various capacities were selected and 54 survey items were selected through evaluation of experts twice. The pilot tests were conducted and targeted at Jeonnam song ho-jung village and Gyeongnam Haegeumgang village to identify derived survey items. In addition, descriptive statistic analysis and reliability analysis were conducted. As a result, survey items were corrected by reducing 10 items of the total 54 items. This results showed that using this tool could help us understand capacity levels of rural residents.

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

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.

TNF-α로 유도된 혈관내피세포의 혈관염증에 미치는 오적산(五積散)의 억제 효과

한병혁 ( Byung Hyuk Han ),윤정주 ( Jung Joo Yoon ),김혜윰 ( Hye Yoom Kim ),안유미 ( You Mee Ahn ),홍미현 ( Mi Hyeon Hong ),손찬옥 ( Chan Ok Son ),나세원 ( Se Won Na ),이윤정 ( Yun Jung Lee ),강대길 ( Ho Sub Lee ),이호섭 대한본초학회 2018 大韓本草學會誌 Vol.33 No.4

Objectives : Ojeoksan, originally recorded in an ancient Korean medicinal book named “Donguibogam” and has been used for the treatment of circulation disorder of blood which was called blood accumulation (血積) in Korean medicine. Therefore, this study was carried out to investigate the beneficial effect of OJS on vascular inflammation in HUVECs. Methods : We evaluated the effect of OJS on the expression of cell adhesion molecules and protective role in HUVEC stimulated by TNF-α by using Western blot. Results : Pretreatment with OJS decreased the adhesion of HL-60 cells to TNF-α-induced HUVEC. OJS suppressed TNF-α-induced expression level of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and endothelial cell selectin (E-selectin). Moreover, OJS significantly decreased TNF-α-induced production of intracellular reactive oxygen species (ROS); and inhibited the phosphorylation of IκB-α in the cytoplasm compared to the experimental group. Pretreatment with OJS inhibited the trans-location of NF-κB p65 to the nucleus. OJS also inhibited phosphorylation of MAPKs compared to the experimental group. OJS significantly increased the protein expression of Nrf2 and HO-1. Conclusions : Ojeoksan has a protective effect on vascular inflammation, and might be a potential therapeutic agent for early atherosclerosis.

<i>Prunella vulgaris</i> Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

Hwang, Sun Mi,Lee, Yun Jung,Yoon, Jung Joo,Lee, So Min,Kim, Jin Sook,Kang, Dae Gill,Lee, Ho Sub Molecular Diversity Preservation International (MD 2012 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.13 No.1

<P>Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from <I>Prunella vulgaris</I> (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS). HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1), eNOS, and nuclear factor E2-related factor 2 (Nrf2), which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that <I>Prunella vulgaris</I> may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.</P>

Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

Choi, Eun Sik,Lee, Yun Jung,Seo, Chang Seob,Yoon, Jung Joo,Han, Byung Hyuk,Park, Min Cheol,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2016 Evidence-based Complementary and Alternative Medic Vol.2016 No.-

<P>Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-<I>κ</I>B) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-<I>κ</I>B and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-<I>κ</I>B was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-<I>κ</I>B translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-<I>α</I> in HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug.</P>

Anti-Proliferative Effect of an Aqueous Extract of <i>Prunella vulgaris</i> in Vascular Smooth Muscle Cells

Hwang, Sun Mi,Lee, Yun Jung,Lee, Yong Pyo,Yoon, Jung Joo,Lee, So Min,Cha, Jeong Dan,Choi, Kyung Min,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenic factor of vascular disorders such as diabetic atherosclerosis. We have reported the anti-inflammatory effect of an aqueous extract from <I>Prunella vulgaris</I> (APV) in vascular endothelial cell. In the present study, APV exhibited inhibitory effects on high glucose-stimulated VSMC proliferation, migration, and invasion activities, inducing G<SUB>1</SUB> cell cycle arrest with downregulation of cyclins and CDKs and upregulation of the CKIs, p21<SUP>waf1/cip1</SUP> and p27<SUP>kip1</SUP>. Furthermore, APV dose dependently suppressed the high glucose-induced matrix metalloproteinase activity. High glucose-induced phosphorylation of ERK, p38 MAPK, was decreased by the pretreatment of APV. NF-<I><I>κ</I></I>B activation by high glucose was attenuated by APV, as an antioxidant. APV attenuated the high glucose-induced decrease of nuclear factor E2-related factor-2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression. Intracellular cGMP level was also increased by APV treatment. These results demonstrate that APV may inhibit VSMC proliferation via downregulating ROS/NF-<I><I>κ</I></I>B /ERK/p38 MAPK pathways. In addition, APV has a beneficial effect by the interaction of Nrf2-mediated NO/cGMP with HO-1, suggesting that <I>Prunella vulgaris</I> may be useful in preventing diabetic atherosclerosis.</P>