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>

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]

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>

척수압박으로 발현된 급성 골수성 백혈병에 동반된 과립구성 육종 1 례

윤상준,김영곤,김희종,박유환,정춘해,김양수,김태균,박영진,전호종 조선대학교 부설 의학연구소 2000 The Medical Journal of Chosun University Vol.25 No.1

저자들은 척수압박으로 하지마비를 보인 환자에서 수술 후에 급성 백혈병에 동반된 과립구성 육종으로 진단된 환자 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Granulocytic sarcoma(GS) is an uncommon tumor composed of immature cells of the granulocytic series. Most case of GS occur in the course of acute leukemia and the blast crisis of chronic leukemia, Rarely, however, it may present before leukemia becomes clinically apparent. It may also occur in patients with myeloproliferative disoders. GS has been reported that it occurs in 3% to 9% of patients with acute myelogenous leukemia(AML) and the incidence of GS is reported to be higher in patients with t(8;21). GS occurs relatively commonly in africa and has been reported to affect 10-25% of black children presenting with AML. This is very rare case of granulocytic sarcoma with AML(FAB M5) presented with spinal cord compression which was supported by decompression laminectomy.

비지의 영양학적 품질특성

김군자,류호경,이영근,김동섭 밀양대학교 농업기술개발연구소 2000 農業技術開發硏究所報 Vol.4 No.1

This study was carried out to examine the qualities of soybean curd residue for utilizing as foodstuff. The content of moisture, crude protein, crude fat and ash were 80.98, 3.32, 0.94 and 0.82%, respectively. The major fatty acids were linoleic acid, oleic acid, linolenic acid and stearic acid. The hydrolysate of protein of sobean curd residue was composed chiefly of aspartic acid, glutamic acid, glycine, alanine, arginine and threonine, but the major free amino acids of soybean curd residue were arginine(234.1), ethanolamine (91.6), γ -amino-n-butyric acid(60.2), glutamic acid(55.8), valine(49.8), asparagine(47.3) and Iycine(48.3μ mol/100g). Key words : Soybean curd residue, Fatty acid, Amino acid

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

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

금 카벤 착체합성 및 특성에 관한 연구

정민철,정혜성,김성민,이정훈,박권필,안호근 한국공업화학회 2005 응용화학 Vol.9 No.1

We have been used for the Pt catalyst of cathode electrode in fuel cell. Weak point of Pt electrode are easily deactivated by the CO poisoning which are producing in reaction at electrode. Recent, researchers have developed cathode electrode to avoid the CO poisoning in electrode using the Pt-alloy or another novel metal. We now report Au-carbene complexes as an Au-electrode precursor derived from the reaction of the carbene with the ClAu(PPh₃) complex in THF/MeOH.

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.

The Study of Refractive Status under Cycloplegic in Young Children

Hoy Sun Shin,Cheol Guen Shin,Gil SeOng Kim,Kyung Ho Sun 대한시과학회 2003 대한시과학회지 Vol.5 No.1

조절작용은 눈의 굴절상태를 변화시킬 수 있는 힘으로 나이가 어리면 어릴수록 이 것을 억제하기가 어렵다. 사람은 나이가 들면서 조절력이 감소되고 조절작용올 억제 하기가 쉬워진다. 기존 연구에서 고둥학교 학생들의 조절마비제 정안 전과 후의 굴절 력의 변화가 적었고 나이가 어릴수록 조절마비제를 이용하여 굴절검사가 이루어져야 한다고 하였다. 이 연구의 대상자들은 부모나 보호자들에 의해 시력장애가 의심되거나 환자 스스 로 시야의 흐립을 호소한 경험이 있는 순천지역 6-9세 사이의 소년 60 t청 (OS)을 대 상으로 하였다. 굴절이상을 제외한 녹내장, 백내장, 망막질환, 약사, 가성근시, 그리고 조절마비는 대상의 생플에서 제외시켰다. 환자들의 내원 당일 타각적과 자각적 방법 으로 현성굴절검사(Manifest Refraction) 와 조절마비제률 이용한 굴절검사( Cycloplegic Refraction)를 하였고, 5 일 후 추적 검사 (Post Cyclo-refraction) 를 하였다. 본 연구에서는 면과 원주요소를 각각 CR과 MR, PCR과 MR, PCR과 CR의 차이를 계산하여 Origin 6.0(paired t-test) 프로그랩올 사용하여 분석 하였다. 그 결과 CR과 MR, PCR과 CR의 차이와 비교하여 MR과 CR의 구면요소 굴절차이가 많은 것으로 나타났다. 그러나 이러한 구면의 차이는 나이가 중가할수록 감소하였다 :6세 (p = 0.03237, t = -3.78325) 와 7세 (p = 0.000245378, t = -5.31없3) 에서 는 유의 하였고 8세 (p = 0.08871, t = -1.97593) 와 9세 (p = 0.48959, t = -0.74536) 에 서 는 유의 하지 않았다. MR과 PC의 구면 차이는 모든 나이에서 통계학적으로 유의하지 않았다. 김의 연구도 또한 MR과 CR의 차이가 7 세 보다 어린 나이에서 굴절력의 차이가 크게 나타났다고 보고 하였다. 결론적으로 각각의 굴절상태 차이에서 구면요소는 나이가 어릴수록 조절성향 이 강한 반면 원주요소는 굴절 변화가 적고 불규칙적이며 불일치성을 보였다 (p< 0.05). 이 결과에 의하여 나이가 어린 환자, 특히 7세 미만에서는 반드시 조절마비제 를 이용한 굴절검사가 이루어져야 하겠다. Accommodation is a variable force capable of changing the refraction of the eye. The younger the subject, the more difficult it is to prevent its action. As a person ages and the amplitude of accommodation decreases, it become easier to suppress accommodative action. The subjects of this study covered sixty boys aged 6-9 years with histoπ of blurring of vision or suspicious visual defect detected by parent or caret삶er rather than themselves were taken from soon-chon area. Other than refractive anomalies such as glaucoma, cataract, retinal disease, amblyopia, pseudo-myopia, and accommodative spasm were disregarded from the case samples. Subjects were examined as routine manifest refraction(MR) in the first visit followed by cycloplegic refraction(CR) which performed on the s없ne date, then followed up after 5 days for post-cycloplegic refraction(PCR). The data were analyzed using ORIGIN 6.0, paired t-test were computed for spherical and cylindrical component of MR from CR, MR from PCR, and CR from PCR. This study has shown that the differences in spherical components CR from routine MR were greater compared to MR from pcR and CR from PCR. But sphere differences decreased as age increased: it was significant at age six(p = 0.03237, t = -3.78325) and seven(p = 0.000245378, t = -5.31없3) whereas it was not significant at age eight(p = 0.08871, t = -1.97593) and nine(p = 0.48959, t = -0.74536). The sphere differences MR from PCR were not statistically significant in all ages. Kim’s study also reported that there were greater refraction differences less than 7 years old than higher ages between MR and CR. However, cylindrical components showed small but irregular and inconsistency with ages under MR from CR, MR from pcR, and CR from PCR. All of the cylinder differences were not statistically significant( p < 0.05). Therefore, it is recommended that cycloplegic refraction should be performed as long as the subjects are young, especially under 7 years old.