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>

<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>

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>

머리염색이 인체에 미치는 영향

윤형식,황성호,이현륭,김수호,박연석,권낙현,정호진,김동훈,노현주,홍성호,박병찬,이관,정해관 東國大學校醫學硏究所 2002 東國醫學 Vol.9 No.1

일상생활에서 모발염색은 흔히 접할 수 있는 미용의 한 종류로 특히 젊은층을 중심으로 폭발적으로 유행하고 있다. 염색을 위항 사용하는 약제는 표백제와 발색제 등 각종 화학약품이 사용되고 있으나 이로 인한 건강장해에 대한 연구는 그리 많지 않다. 저자들은 염색이 인체의 모발건강에 미치는 영향을 파악하기 위하여 염색과 관련된 주관적 증상과 모발의 변화에 대한 실험적 연구를 시행하였다. 동국대학교 경주 캠퍼스 재학생 80명을 대상으로 설문조사를 시행하여 염색 유 ·무 및 염색 후에 경험한 증상에 대해 설문 조사하였고, 의과대학 재학생 46명을 대상으로 피부 반응 테스트를 실시하였다. 또한 염색 전후의 모발 탄성도를 측정하였고 모발의 상태를 파악하기 위해 전자 현미경검사를 실시하였다. 설문조사 결과 염색 전에 비하여 염색 후 안구혼탁, 안구건조, 시력저하, 발진 및 접촉성 피부염, 모발손상, 모근손상 등의 증상을 더 많이 경험한다고 호소하였다(p<0.05). 모발손상과 모근손상은 헤어드라이어 사용 빈도에 따라 증가하는 것으로 조사되었다(p<0.05). 피부반응검사에서 가려움증이 가장 많은 증상이었으며 이는 여성보다는 남성에서 높은 것으로 조사되었다. 염색 전후의 모발장력은 염색 전 134.5±10.37g, 염색 128.0±30.69g, 염색 이틀 후 112.5±19.69g으로 나타났다. 염색 전후의 모발의 전자현미경 케라틴 층이 현저히 감소하고 모발이 가늘어지는 차이를 보였다. 염색은 모발손상, 모발 케라틴 손상 및 모근 손상, 발진 및 접촉성 피부반응, 안구혼탁, 안구건조, 시력 저하를 유발한다. 따라서 염색약으로 인한 손상에 대한 주의와 예방이 필요하다고 생각한다. 예방대책으로 염색 전 피부테스트를 통한 적합성 여부를 판단하는 것이 필요하며 가급적 염색을 피하는 것이 좋을 것이다. 염색약에 발암물질이 포함되어있다는 보고도 있어 염색 제조사의 철저한 실험과 염색 물질의 선별이 염색으로 인한 부작용을 최소화하는데 중요한 역할을 할 것이다. Hair coloring has became one of the most popular cosmetic activities to younger generations during last decade. However, there are few studies on the health effect of widespread use of chemical dyes. This study was conducted to study the effects of hair coloring dye on hair and other systems. We conducted a questionnaire survey of 80 persons in Kyongju campus, Dongguk University. We have done open patch skin test on 46 medical students. We also conducted scanning electron microscopy to examine the hair strength and structure before and after hair coloring process. Injury of hair and hair bulb, contact dermatitis, turbid eyes, xerophthalmia, and poor visual acuity were the main symptoms complained after hair coloring (p<0.05). Injury of hair and hair bulb were increased by frequency of hair-dryer use(p<0.05). In open patch test, pruritus was complanined by more than half of the subjects. Mean strength of hairs before and after hair coloring was as follows; 134.5 (SD 10.37)g before hair coloring, 128.0 (SD 30.69)g immediately after hair coloring, and 112.5 (SD 19.69)g after two days. The scanning electron microscopic findings of hair surface before and after hair coloring showed decreased keratin layer and thinning of the hair. Hair coloring induces injury to hair, its keratin layer, and hair bulb as well as contact dermatitis, turbid eyes, xerophthalmia, and poor visual acuity. Therefore, we think that precaution is needed in use of hair coloring dye. To prevent complications induced by hair coloring dye, it is necessary, especially to those with allergy or skin disorders, to perform skin test before action and avoid hair coloring whenever possible. Longterm health effects of hairdye should be studied and manufacturing companies should try to minimize complications induced by hair coloring dye.

구강 악성 흑색종에서 PCNA 발현에 관한 면역조직화학적 연구

황경균,남윤우,이재일,이종호,심광섭,김명진 大韓顎顔面成形再建外科學會 2002 Maxillofacial Plastic Reconstructive Surgery Vol.24 No.6

Malignant melanoma arising from the mucosa of head and neck region was rare and showed poor prognosis. Some of malignant melanoma were transformed from benign melanotic lesion. Malignant melanoma had high cellular proliferation and rapid growth. The percentage of PCNA-positive cell (labeling index) is high in many malignant tumor. So we compared the pattern of PCNA expression in the melanotic lesion. We performed the immunohistochemical study in malignant melanoma(19 cases), benign melanotic macule(24 cases) and normal mucosa(20 cases) were diagnosed in Seoul National University Dental Hospital between 1980 and 2000. Positive PCNA staining was found mainly in malignant melanoma. The mean PCNA expression in malignant melanoma, melanotic macule, normal tissue were 29.2%, 1.4%, 0%, respectively. Significant differences in PCNA expression were noted between malignant melanoma and melanotic macule(p<0.01), normal mucosa(p<0.01). These result suggested that the PCNA expression seems to be used as a diagnostic indicator for malignancy in malignant melanoma and melanotic lesion.

프리캐스트 포스트텐션 콘크리트 넓은 보-기둥 내부 접합부의 비탄성 거동

황재환,최윤철,김영찬,김대중,임재형,권기혁,문정호,이리형 대한건축학회 2003 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.23 No.2(구조계)

The purpose of this paper is to evaluate the response of Precast Prestressed Concrete Interior Wide Beam-Column Joint subjected to cyclic lateral loading. To this end, the experimental investigation was performed with six half-scale specimens of interior connection. The design parameters are the beam to column depth ratio, and the number of tendons within column core. One of the specimens, IJH-6, is modeled for the connection at the top floor of a structure. The test results showed that the specimens sufficiently resist up to limiting drift ratio of 0.035 in accordance with the provisional standard by ACI of acceptance criteria for concrete special moment frames.

건설사업에서 사업타당성 분석모델구축을 위한 위험 요소 구분에 관한 연구

황윤재,박영호,백준홍 대한건축학회 2003 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.23 No.2

The Purpose of this study is to classify the Risk Factors in Construction Projects. The Classified Risk Factors are used for Building a specific Feasibility Analysis Models. Generally, The Success of Construction Projects depends on how to Plan, Prepare and Analysis the whole project in the beginning Phase. One of Characteristics in Construction Projects are Uncertainties and Risks which are managed and analyzed in a Pre-designed phase. Also The Feasibility Analysis anticipates the whole incomes and outlays of Projects in the beginning phase. In these reasons, The Feasibility Analysis Modeling is the important process in Construction Projects. In this paper, Re-arrange the entire Construction-Risk Factors for Building an realistic and reasonable Feasibility Analysis Model in future studies.

하악 대구치 Ⅱ형 근심 근관에서 치근단 부위의 만곡도 조사

윤혜림,이동균,황호길 大韓齒科保存學會 2012 Restorative Dentistry & Endodontics Vol.37 No.2

Objectives: The purpose of this study was to evaluate the buccolingual curvature at the apical one third in type Ⅱ mesial canals of mandibular molars using the radius and angle of curvature. Materials and Methods: Total 100 mandibular molars were selected. Following an endodonticaccess in the teeth, their distal roots were removed. #15 H- or K-files (Dentsply Maillefer) were inserted into the mesiobuccal and mesiolingual canals of the teeth. Radiographs of the teeth were taken for the proximal view. Among them, type Ⅱ canals were selected and divided into two subgroups, Ⅱa and Ⅱb. In type Ⅱa, two separate canals merged into one canal before reaching the apex and in type Ⅱb, two separate canals merged into one canal within the apical foramen. The radius and angle of curvature of specimens were examined. Results: In type Ⅱ, mean radius of curvature in mesiolingual and mesiobuccal canals were 2.82 mm and 3.58 mm, respectively. The radius of the curvature of mesiolingual canals were significantly smaller than that of mesiobuccal canals in type Ⅱ, and especially in type Ⅱa. However, there were no statistically significant differences in radius of curvature between mesiobuccal and mesiolingual canals in type Ⅱb and there were no significant differences in angle of curvature between type Ⅱa and Ⅱb. Conclusion: In this study, type Ⅱ mesial canals of mandibular molars showed severd curvature in the proximal view. Especially, mesiolingual canals of type Ⅱa had more abrupt curvature than mesiobuccal canals at the apical one third.

여름 고추육묘의 트라이졸계 처리에 의해 유기된 생육억제 해소에 관한 연구

채윤석,강호종,황서진 진주산업대학교 농업기술연구소 2007 農業技術硏究所報 Vol.20 No.-

고온기 고추육묘에 처리한 생장억제제 처리 효과 및 정식 후 생육억제를 회복하기 위하여 GA, 관수, 고온처리 효과에 대한 연구 결과는 다음과 같다. 1.생장억제제 트리아졸계 처리 횟수에 따라 초장 및 주경장은 뚜렷한 차이를 나타냈고 근장도 2회 처리를 함으로 1회 처리를 한 것보다 발달하지 않았다. 2. 왜화된 고추묘의 생육억제 해소에 미치는 영향은 초장 및 주경장의 생장에는 GA처리구가 뚜렷하였으나 다른 처리구는 비슷한 경향이었고 경경은 변화가 없었다. 3. 생육회복을 위한 처리별 생체 및 건물중은 정식 후 30일까지는 변화가 거의 없었으나 그 후 45일까지 급격히 증가하였는데 고온 및 관수처리구에서 뚜렷한 차이를 보였으며 45일 이후에는 모든 처리구에서 비슷한 경향을 보였다. 4. 정식 45일 경 처리구간 엽록소 함량은 GA처리구에서 가장 낮았으며 다른 처리구간에는 비슷했다. This study was carried out to find effects of restoration of hot pepper seedling dwarfed by the treatment of diniconazole by introducing GA₃, Irrigation and high temperature at knight and the results obtained are summarized as follows. The main results of this research are summarized as follows. 1. In the case of plant height and main stem hight treated with the first time and second time diniconazole showed the strongest effect than untreatment. The root length treated with diniconazole the first time effect gradually disappeared than the second time. 2. Sprays of GA₃100ppm to the dwarfed seedlings by diniconazole pretreatment were effective in counteracting the plant height and main stem height growth inhibition caused by diniconazole pretreatment. 3. The fresh and dry weight of pepper seedling were not significantly different untill 30days in planting, but were increased to 45days from 30days in planting. 4. The chlorophyll content were decreased more or less treatment of GA₃ 100ppm after 45days in planting.