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>

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>

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.

지방자치시대의 지역복지전달체계 확립방안 : 효율적인 공적복지전달체계 구축을 중심으로

최용호,박근수,노병수 朝鮮大學校 社會科學硏究所 2003 社會科學硏究 Vol.24 No.2

남자 초·중·고등학생의 최대 산소섭취량 추정에 관한 연구

신호수,이병근,전태원 師範大學 體育硏究所 1992 서울大學校 體育硏究所論集 Vol.13 No.1

The purpose of this study was to produce regression equation of VO₂max prediction appropriated to elementary, middle and high school male students, and to eveluate the validity of their predictions. The predictions of VO₂max (ℓ/min, ml/㎏/min and ml/FFW/min) were obtained by multiple regression procedures from a sample of 53 students, aged 7∼17 years. The prediction for VO₂max were obtained from the subjects’age, height, weight,% fat and fat-free weight. From the result of multiple regression for VO₂max, the following equations were obtained. ------------------------------------------------------------------------------- Inde. Vari No Prediction equations ------------------------------------------------------------------------------- 1 1.554+0.060*AGE-0.011*HT+0.062*WT-0.033*%FAT-0.014*FFW VO₂max ℓ/min 2 0.559+0.047*WT-0.024*%FAT 3 -0.507+0.038*AGE+0.004*HT+0.034*WT ------------------------------------------------------------------------------- 4 74.32+0.959*AGE-0.167*HT+0.208*WT-0.640*%FAT+0.209FFW VO₂max 5 59.13-0.513*%FAT ㎖/kg/min 6 34.68+0.618*AGE+0.118*HT-0.293*WT ------------------------------------------------------------------------------- 7 95.22+1.707*AGE-0.276*HT+1.192*WT-0.588*%FAT-1.48*FFW VO₂max 8 64.92+0.618*HT-0.914*FFW ㎖/FFW/min 9 60.25+0.311*AGE+0.100*HT-0.276*WT ------------------------------------------------------------------------------- The multiple correlations and relative errors of estimate for the predictions in ℓ/min (No.1.2.3) were quite similar (R=0.96, 0.96,0,92; CV=±9.5%, ±9.5%, ±10.1%). The multiple correlations for the prediction in ml/㎏/min (No.4,5,6) were quite different (R=0.45, 0.41, 0.29), but the relative errors of estimation, ±9.9%, ±10.1% and ±10.6% respectively, were quite similar. The multiple correlations and relative errors of estimate for the predictions in ml/FFW/min (No.7,8,9) were quite similar (R=0.68, 0.62, 0.45; CV= ±9.3%, ±10.2%, ±11.6%). The validity of prediction equations was tested from the validity group (7∼17 years, 19boys). It is 0.92∼0.94 for equation 1∼3, 0.50∼0.65 for equation 4∼6, and 0.59∼0.64 for equation 7∼9. Their prediction equations were quite stable, % errors approximately -0.8∼-3.2%. It indicated that the predictive equations in this study provide more reliable than the Astrand-Ryhming nomogram and that reasonably and accurate of VO₂max for the male students may be obtained from their age, height, weight, %fat and fat-free weight.

만곡근관의 확대시 기구에 따른 형태변화에 관한 연구

황호길,신영근,이석종 大韓齒科保存學會 1999 Restorative Dentistry & Endodontics Vol.24 No.3

X-선 발생장치 시설의 방사선 차폐 해석

문석형,최호신,권석근,육종철 대한방사선 방어학회 1987 방사선방어학회지 Vol.12 No.1

X-선 발생장치 시설에 대한 방사선 차폐해석은 두가지 측면에서 고려된다. 먼저 1차 방사선과 누설방사선에 의한 영향을 고려하여야 하며 본 연구에서는 NCRP-49 및 51에 제시된 방법을 사용하였다. 둘째, 시설의 미로 출입구에서는 산란방사선에 의한 영향이 보다 중요한데, 본연구에서는 이 영향을 평가하기 위하여 Albedo개념을 근거로 한 단순한 방법이 제시되었고, 이를 토대로 계산된 결과를 컴퓨터 코-드(MORSE-CG)의 계산치 및 실측된 결과와 비교하였다. 본 연구에서 제시된 방법에 의한 결과는 미로출입구 안쪽의 경우에 대한 해석에서는 약간의 오차를 보이고 있으나 미로출입구 문바깥에서는 비교적 잘 일치한다. 여기서 출입문바깥의 경우에 대한 해석이 방사선방어 측면에서 보다 중요하다는 관점에서 볼 때 이 방법은 의료용 또는 산업용의 X-선 및 감마선시설의 차폐설계 및 해석이 응용될 수 있을 것이라고 판단된다. Radiation shielding analysis for a 6MeV X-ray facility was carried out. The primary and leakage radiation for the facility can be evaluated based on the methodology in NCRP No. 49 and 51. The present study deals with radiation scattering analysis for the outside and inside door of the facility based on the albedo concept. The calculated dose rates were compared with the results of MORSE-CG code calculation and the measured data, resulting in a good agreement, even though there existed some deviation for the inside door. These results can be utilized to the radiation shielding design of the medical and industrial X and gamma ray facilities, and to the safety evaluation of these facilities.

오존산화된 이축연신폴리프로필렌의 열자격 전류 특성

李永俊,李根鎬,金熙東,李元宰,姜道烈 弘益大學校 1988 弘大論叢 Vol.20 No.2

In this paper, Thermally stimulated current(TSC) spectrum was mearsured as a function of formation temperature, formation time, formation voltage and heating rate in a biaxially oriented polypropylene film of thickness 40[μm], which is better than polyethylene in the enduring characteristic against heat and dielectric characteristic, the variation of the TSC was observed by ozone oxidation. This measurment has been carried out in the temperature range from-40[℃] to 140[℃]. As results of the measurment, A,B,C,D peaks was made at 0[℃], 40[℃], 80[℃], 120[℃], respectively. B peak was made at the near second glass transition temperature is estimated the dipole polarization by microbrown motion, C peak is estimated to the polarization of ionic space charge. And, In according to the increase of oxidation time by ozone, B peak increased slowly and C peak increased rapidly after it increased slowly during first oxidation time of 15[Hr]. By initial rising method, activation energies of B,C peaks were calculated to about 0.57, 0.84eV, respectively. The hopping distance and mobility of C peak for pure specimen and ozone oxidated specimen 54A, 71A and 1.099×10??cm²/υ·s, 8. 55×10??cm²/υ·s, respectively.

경부의 범발성 특발성 골격과골 증후군에 의한 연하곤란 : 1례 보고 A Case Report

김영우,장호근,정종철,이기병 대한척추외과학회 2003 대한척추외과학회지 Vol.10 No.3