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>

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.

커패시터 放電 임펄스 着磁機 및 着磁 요크시스템의 定數算定에 관한 硏究

白壽鉉,金 龍,金必洙,尹秀鳳,朴永浩,尹信容 동국대학교 대학원 1992 大學院硏究論集-東國大學校 大學院 Vol.22 No.-

In a capacitor-discharge impulse magnetizer, a magnet is magnetized by the discharging current of capacitor The actual construction of magnetizing fixtures and discharge matching is expensive and time-consuming. Since the parameters of the impulse magnetizer have been determined and the resistance and inductance of such a magnetizing fixture can be easily computed using FEA, it is possible to predict the performance of such a fixture without actually building it. This paper describes that by mathematically modeling the capacitor-discharge impulse magnetizer fixture the problem can be solved with resonable predictability. The basic equations are presented and used to predict the magnetic-field intensity inside the fixtures. Finite-Element-Analysis is also used as part of the design process

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.

Cadmium Sulfate가 肝組織에 미치는 影響에 관한 形態學的 硏究

윤강호,박경란,김수일,노승무,김원식 충남대학교 의과대학 지역사회의학연구소 1991 충남의대잡지 Vol.18 No.2

Cadmium is well known toxic heavy metal which has been related with various pathologic conditions of liver, kindney, testis, cardiovascular system and central nervous system etc.. In this experiment, cadmium sulfate (1.2mg/100gm b.w.) was given intravenously into the mouse (Balb - C, b. w. 20 - 25gm) via tail vein for the study on morphological changes of liver. On the 8hours, 16hours and 24hours after administration, mice were sacrificed under ether anesthesia, liver was removed, then, a part of liver was fixed in 10% neutral buffered formalin solution, processed routinely, stained with hematoxylin & eosin, and observed under light microscope. Otherwise, the remainder portion of liver tissue was prefixed in 1.5% glutaraldehyde solution, postfixed in the 1% osmium tetraoxide solution, embedded with Epon 840, and observed under transmission electron microscope(H-7000, Hitachi Co.). The results obtained were as followings ; 1. On light microscopic observation, hemorrhagic necrosis at the zone Ⅰ and zone Ⅱ with congestion of hepatic lobules were found. 2. On transmission electron microscopic observation, cisternal dilation of RER & SER, autophagic vacuoles, myelin figures, and certain electron dense materials within the hepatocytes were found. Although this observations were limited in mice, the above findings of its acute effects on liver morphology will serve morphological basis for the better understanding of toxic effects on liver after chronic exposure or multiple interactions with other toxic substances.

성견 하악의 치주-치근단 실험적 복합병소에서 골조직 재생에 관한 연구

윤수한,백승호,김정혜 大韓齒科保存學會 1999 Restorative Dentistry & Endodontics Vol.24 No.2

고칼륨혈증에서 심전도의 진단적 의의

윤수영,박원녕,정성필,김승호,이한식 대한응급의학회 2000 대한응급의학회지 Vol.11 No.3

Background: Hyperkalemia is a common and potentially life-threatening metabolic disorder. The electrocardiogram(ECG) is known to be a relatively sensitive diagnostic tool for hyperkalemia. However many exceptions, in which patients showed normal ECG findings even though hyperkalemic, have been reported. The purpose of this study was to determine the extent of correlation between the ECG findings and hyperkalemia and to determine when the ECG has value for diagnosing hyperkalemia. Methods: Patients who had been diagnosed as having hyperkalemia at two university hospitals during three years were enrolled in this study. We reviewed the medical records of the patients and evaluated the following 6 ECG abnormalities: tall T waves, narrow T waves, QRS widening, atrioventricular block, loss of P waves, and sine waves. We defined tall T waves and narrow T waves as 20 percentiles of heights and widths of the T waves from the 100 patients with normokalemia. Results: During the study period, there were 100 hyperkalemic patients, and we analyzed 69 available electrocardiograms. Abnormal ECG findings were revealed in 67%of 69 patients. The higher the serum potassium level, the more abnormal ECG findings. The common ECG abnormalities were tall T waves and loss of P waves. The patients with normal ECGs even though hyperkalemic had relatively low potassium levels. And whether chronic renal disease was not correlated to the ECG abnormality. Conclusion: The electrocardiogram is a good diagnostic tool for hyperkalemia if it is used with accurate diagnostic criteria. Thus, hyperkalemia should be considered when the ECG shows tall T waves or loss of P waves.

수산화세륨(Ⅲ)으로부터 질산암모늄세륨(Ⅳ)의 제조

윤호성,김철주,이진영,김성돈,김준수,유승준 한국화학공학회 2003 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.41 No.3

본 연구에서는 수산화세륨으로부터 질산세륨 용액 제조 후 질산암모늄 첨가에 의한 질산암모늄세륨 제조시, 출발용액의 산도와 농도 그리고 질산암모늄 첨가량, 반응온도 및 반응시간이 질산암모늄세륨 합성에 미치는 영향을 고찰하였으며, XRD, SEM 그리고 TGA 분석을 통하여 결정의 형태 및 구조에 대한 고찰을 수행하였다. 4가의 수산화세륨을 질산에 용해한 질산세륨(Ⅳ)수용액으로부터 질산암모늄 첨가에 의한 질산암모늄세륨 제조시 회수율을 고려한 최적 합성조건은 출발물질의 세륨 농도 70-100g/l, 출발용액의 산도 7 mol/l, 질산암모늄 첨가량 2.5당량, 감압·가열온도 65℃ 및 반응시간 15-30min.이었으며, 제조된 질산암모늄세륨의 결정 화학식은 (NH_4)_2[Ce(NO_3)_6) · ×H_2O(x=6-8)인 것을 알 수 있었다. Synthetic process of ammonium cerium nitrate from cerium hydroxide was presented and influences of concentration and acidity of starting solution, addition quantity of ammonium nitrate, reaction temperature, reaction time on the yield of ammonium cerium nitrate are discussed. The shape and composition of crystal were determined by SEM, thermogravimetry differential thermal, x-ray diffraction and chemical analysis. The optimum synthesizing conditions of ammonium cerium nitrate were discribed as follows; rare earth concentration of starting solution 70-100 g/l. acidity of starting solution 7 mol/l, addition quantity of ammonium nitrate 2-3 equivalent, the condition of rotary evaporation 65℃ and reaction time 15-30 min. It was also known that the chemical formulae of ammonium cerium nitrate was (NH_4)_2[Ce(NO_3)_6] ·×H_2O(x=6-8) from TGA.

고효율 DC/DC컨버터 제작을 위한 동기정류기 도전 손실 해석

윤석호,김용,백수현,김필수 동국대학교 산업기술연구원 1999 산업기술논문집 Vol.14 No.-

최근 반도체 소자의 제조기술 발달로 정보통신기기 등에 사용되는 온보드(on-board) 컨버터의 전원전압은 3.3V 또는 1.5V의 저전압 전원이 사용된다. 이러한 저전압 전원방식은 온보드(on-board) 컨버터의 정류기단 전력손실이 증가하게 되어 시스템의 높은 효율을 얻기가 어렵게 된다. 낮은 전원전압 방식일수록 정류기단에서 전력손실은 더욱 증가하여 컨버터의 효율은 낮아진다. 고전력밀도의 정류기단 구성을 위하여 출력단에 다이오드 대신 MOSFET 자기구동 정류기를 사용한다. 그러나 MOSFET 자기구동 정류기의 전력손실은 2차측 구동전압의 형태나 기생인덕턴스의 영향을 받게 된다. 따라서 불연속에서는 기생인덕턴스에 의한 MOSFET와 쇼트키 다이오드의 도통주기의 변화가 MOSFET 자기구동 정류기의 전력손실에 미치는 영향을 분석하였으며, 그 결과 기생인덕턴스의 크기를 감소시켜 MOSFET의 도통주기를 증가시킴으로써 MOSFET 자기구동 정류기의 전력손실을 최소화하였다. Recently, new trend in telecommunication device is to apply low voltage, about 3.3V-1.5V. However, it is undesirable in view of high efficiency and power desity which is the most important requirement in the distributed power system. Rectification loss in the output stage in on-board converter for distributed power system are constrained to obtain high efficience at low output voltage power supplies. This paper is investigated conduction power loss in synchronous rectifier with a parallel connected Schottky Barrier Diode(SBD). Conduction losses are calculated for both MOSFET and SBD respectively. The SBD conduction power loss dissipates more than the MOSFET rectifier conduction power loss.