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]

Comparison of trophic factors changes in the hippocampal CA1 region between the young and adult gerbil induced by transient cerebral ischemia.

Yan, Bing Chun,Park, Joon Ha,Kim, Sung Koo,Choi, Jung Hoon,Lee, Choong Hyun,Yoo, Ki-Yeon,Kwon, Young-Geun,Kim, Young-Myeong,Kim, Jong-Dai,Won, Moo-Ho Kluwer Academic/Plenum Publishers 2012 Cellular and molecular neurobiology Vol.32 No.8

<P>In the present study, we investigated neuronal death/damage in the gerbil hippocampal CA1 region (CA1) and compared changes in some trophic factors, such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), in the CA1 between the adult and young gerbils after 5 min of transient cerebral ischemia. Most of pyramidal neurons (89%) were damaged 4 days after ischemia-reperfusion (I-R) in the adult; however, in the young, about 59% of pyramidal neurons were damaged 7 days after I-R. The immunoreactivity and levels of BDNF and VEGF, not GDNF, in the CA1 of the normal young were lower than those in the normal adult. Four days after I-R in the adult group, the immunoreactivity and levels of BDNF and VEGF were distinctively decreased, and the immunoreactivity and level of GDNF were increased. However, in the young group, all of their immunoreactivities and levels were much higher than those in the normal young group. From 7 days after I-R, all the immunoreactivities and levels were apparently decreased compared to those of the normal adult and young. In brief, we confirmed our recent finding: more delayed and less neuronal death occurred in the young following I-R, and we newly found that the immunoreactivities of trophic factors, such as BDNF, GDNF, and VEGF, in the stratum pyramidale of the CA1 in the young gerbil were much higher than those in the adult gerbil 4 days after transient cerebral ischemia.</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>

AN IN-SITU YOUNG'S MODULUS MEASUREMENT TECHNIQUE FOR NUCLEAR POWER PLANTS USING TIME-FREQUENCY ANALYSIS

Choi, Young-Chul,Yoon, Doo-Byung,Park, Jin-Ho,Kwon, Hyun-Sang Korean Nuclear Society 2009 Nuclear Engineering and Technology Vol.41 No.3

Elastic wave is one of the most useful tools for non-destructive tests in nuclear power plants. Since the elastic properties are indispensable for analyzing the behaviors of elastic waves, they should be predetermined within an acceptable accuracy. Nuclear power plants are exposed to harsh environmental conditions and hence the structures are degraded. It means that the Young's modulus becomes unreliable and in-situ measurement of Young's modulus is required from an engineering point of view. Young's modulus is estimated from the group velocity of propagating waves. Because the flexural wave of a plate is inherently dispersive, the group velocity is not clearly evaluated in temporal signal analysis. In order to overcome such ambiguity in estimation of group velocity, Wigner-Ville distribution as the time-frequency analysis technique was proposed and utilized. To verify the proposed method, experiments for steel and acryl plates were performed with accelerometers. The results show good estimation of the Young's modulus of two plates.

A Case of Urethral Stent for Recurrent Urethral Stricture and Penile Prosthesis for Erectile Dysfunction

Jung, Gyung-Woo,Song, Young-Jin,Park, Young-Ho,Kwon, Heon-Young,Yoon, Jin-Han 동아대학교의과대학 1992 동아의대학술지 Vol.4 No.1

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.

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>

감사품질이 회계의 보수성에 미치는 영향

정호영(Jung, Ho-young),정재권(Jeong, Jae-kwon) 글로벌경영학회 2008 글로벌경영학회지 Vol.5 No.4

회계처리 보수성과 회계감사의 질적 수준을 나타내는 감사품질과 관련된 정보는 자본시장에서 이해관계자의 의사결정에 매우 유용하고 신뢰성이 있는 회계정보로써 인정되고 있다. 그러나 그동안 감사품질과 회계처리 보수성과의 관계에 대한 국내연구가 희소하고, 연구결과 또한 일관된 내용을 보고하고 있지 않다. 따라서 이러한 문제를 해결하기 위해 감사품질 주요 특성들과 회계처리 보수성이 어떤체계적인 관련성을 가지는가를 살펴보기 위한 실증분석을 실시하였다. 본 연구에서 연구가설검증을 위한 감사품질의 특성은 감사인 규모(Big4제휴법인과 Non-Big4제휴법인)와 감사투입시간 및 감사위원회를 각각 관심변수로 하고 Givoly and Hayn.(2000)의 음(-)의 비영업발생액을 이용하여 측정한 회계처리 보수성을 종속변수로 하는 다변량 회귀분석을 실시한다. 또한 실증연구를 위한 표본은 2001년부터 2006년까지 기간 동안 유가증권시장에 상장된 3,540개(기업-년)의 제조기업 중에서 최종․선정된 2,573개(기업-년)를 대상으로 하였다. 연구결과는 다음과 같다. 첫째, 연구가설 설정 시에 예상한 바와 같이 Big4제휴법인이 감사한 기업들의 회계처리 보수성이 Non-Big4제휴법인이 감사한 기업들의 회계처리 보수성보다 더 높게 나타났다. 둘째, 감사투입시간과 회계처리 보수성의 관계는 예상과 다르게 유의성이 있는 음(-)의 관련성을 보이고 있는 것으로 나타났다. 셋째, 감사위원회와 회계처리 보수성과의 관계는 5% 수준에서 유의한 양(+)의 관련성을 가지고 있는 것으로 나타났다. 이는 회계처리 보수성을 투명성과 신뢰성의 대용치로 간주할 때, 감사위원회 구성원 중 독립적인 사외이사 비중이 높을 경우 회계처리 보수성 증가로회계분식의 가능성이 감소한다는 의미로 볼 수 있다. 본 연구는 감사인 유형에 한정하여 회계처리 보수성과의 관계를 연구한 기존의 연구를 더욱 확장하였다. 또한 연구대상기간도 선행연구와는 다르게 감사품질이 집중적으로 논의된 2001부터 2006년까지로 하였다. 더욱이 선행연구에서 사용한 소수의 통제변수가 갖는 누락변수문제로 인한 측정오차의 문제를 완화하고자 하는 동기에서 회계의 보수성에 영향을 미칠 것으로 추정되는 다양한 통제변수들을 선정․활용하여 검증활동을 수행하였다. 따라서 본 연구의 결과는 회계감사실무에서나 자본시장에서 이해관계자의 의사결정에 매우 유용한 회계정보로 사용될 수 있을 것으로 기대된다. The accounting information which relates with the audit quality and the accounting conservatism which becomes known as the means which secures the transparency and the reliability of accounting is very useful in decision of stake-holders from capital market in actuality. But in the meantime, the domestic research against the relationship with audit quality and accounting conservatism is rare. This study executes the multi-variable regression of dependent variable which it consist of auditor size(Big4 member firms and Non-Big4 member firms) and audit service time and audit committee, of independent variable which is accounting conservatism which it measures with the measurement method which uses the negative(-) non-operating accruals of Givoly and Hayn(2000). Also the sample for an empirical testing are selected 2,573(firm-years) from in 3,540(firm-years) manufacture enterprises which listed on the Korea Stock Exchange in the period from 2001 to 2006. Major findings of the study include the followings. The first, the accounting conservatism of the Big4 member firms appeared more highly than the Non-Big4 member firms. The second, audit service time shown the negative(-) relationship of accounting conservatism. The third, The relationship of accounting conservatism and audit committee had the relation of the positive(+) which considers from significant(5% level) statistically. I expected, When regarding as that accounting conservatism was the same transparency and reliability, the possibility of accounting fraud decreased through accounting conservatism increase in the case which audit committee would be composed of the independent director. This study expanded more than prior study which it researched only the relationship of auditor types and accounting conservatism, through an systemic testing on what accounting conservatism related to audit quality(not audit size but audit service time and audit committee). Also the research period did with preceding research from 2001 to 2006, when audit quality is intensively discussed. It relaxed the problem of the error of measurement which is caused by the omitted variable problem because it uses more control variable differently than prior study did. Therefore, The result of this study is expected that it could be used in actuality on decision making of the interested parties in the audit practical affairs and the capital market with a useful information of accounting.

문화재 안내문과 공공언어

권미영(Kwon Mi?young),신언호(Shin Eon?ho) 인천대학교 인천학연구원 2019 인천학연구 Vol.30 No.-

동일한 환자에서 조혈모세포이식 전후의 호중구감소 기간 중 감염양상에 대한 비교연구 : 중심정맥관 관련 패혈증을 중심으로 Based on Central Venous Catheter Related Septicemia

류재호,노규태,이영석,이영호,권혁찬,김재석,김효진,이영민,박혜원,박근희 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.1

연구배경: 동일한 환자를 대상으로 조혈모세포이식 전 일반 병실에서의 관해유도 항암제치료 및 강화요법으로 인한 호중구감소 기간의 감염양상과 고용량 항암제치료 후 무균실에서의 조혈모세포이식 시 호중구감소 기간의 감염양상을 중심정맥관 관련 패혈증을 중심으로 비교 연구함으로써 효율적인 감염관리지침을 마련하고자 하였다. 대상 및 방법: 1999년 1월부터 2001년 7월까지 2년 7개월간 동아대학교병원 일반병실에서 악성혈액질환으로 항암제 치료를 받다가 조혈모세포이식을 시행받았던 22명을 대상으로 중심정맥관 관련 패혈증의 형태를 비교분석하였다. 결과: 대상 환자들의 일반병실과 무균실에서의 입원기간은 각각 32±13일, 33±19일, 호중구 감소기간은 15±12일, 17±18일, 호중구 감소기간의 발열 횟수는 14회, 14회로서 입원병실의 종류에 따른 차이는 없었다. 환자들의 중심정맥관 사용일수는 일반병실에서 29일(7~545일), 무균실에서 100.5일(25~606일)이었으며, 총 사용일수는 각각 1,515일, 3,250일로서 무균실에서의 중심정맥관 사용일수가 의미 있게 길었다(P=0.001). 중심정맥관 사용 일수에 대한 감염률은 각각 5.28/1,000일, 3.08/1,000일로서 일반병실에서 그 빈도가 높았으나 통계적 유의성은 보이지 않았다(P=0.141). 결론: 중심정맥관 삽입 후 일반병실에서 항암제 치료를 받던 환자가 조혈모세포이식을 위하여 무균실에 입원하는 경우, 중심정맥관을 교체하는 것이 감염관리를 위하여 바람직할 것으로 생각된다. Background: We compared the incidence of central venous catheter (CVC) related septicemia during neutropenic period in the same patient, which developed following chemotherapy for remission induction and consolidation, or hematopoietic stem cell transplantation (HSCT). Methods: We retrospectively reviewed the medical records and laboratory data of 22 patients with hematologic malignancies who received anticancer chemotherapy followed by HSCT at Dong-A University Hospital between January, 1999 and July, 2001. We investigated the duration of hospitalization, duration of neutropenic period, duration of catheterization, microbiologically documented organisms and incidence of CVC related septicemia. Results: The data in general ward (before HSCT) and laminar air flow room (after HSCT) were as follows: duration of hospitalization was 32±13 days and 33±19 days, duration of neutropenic period was 15±12 days and 17±18 days, median duration of catheterization was 29 days (7~545 days) and 100.5 days (25~606 days) (P=0.001), and incidence of CVC related septicemia was 5.28/1000 days and 3.08/1000 days, respectively. In the CVC related septicemia, the most common etiologic organism was coagulase negative staphylococcus. Conclusion: We suggest that the exchange of CVC before admission to laminar air flow room could decrease the incidence of CVC related septicemia in HSCT recipients.