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>

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>

급성신부전증 이환견에 대한 복막투석 치료 1례

김건우,이병희,김유수,심재현,김지용,이영원,김덕환,송근호 충남대학교 수의과대학 동물의과학연구소 2004 動物醫科學硏究誌 Vol.12 No.-

A fourteen-month-old intact female Poodle was referred to the Veterinary Teaching Hospital, College of Veterinary Medicine, Chungnam National University. The patient was presented with history of vomiting, inappetence, ataxia, insomnia, tachypnea and convulsion for 5 days. Biochemical examination revealed BUN (254.2 mg/dl), creatinine (9.22 mg/dl) and phosphate (14 mg/dl). Epithelial cells of urinary tract, neutrophils, macrophages, a large number of gram negative and smaller number of gram positive bacteria were presented on urine test. Ultrasonographic findings show hyperechogenic kidney and indistinguishableness of renal cortex and medulla. Based on the results of examination described above, this case was diagnosed as acute renal failure with interstitial nephritis by urinary tract infection (UTI). Treatments with fluids therapy, diuretics, and peritoneal dialysis during hospitalization showed good results with no clinical signs.

당뇨병성 합병증을 가진 환자에서 혈중 Erythropoietin 농도

김동규,유기동,허광식,김상용,윤성호,조영신,권용은,김태원,김건영,정종훈,배학연 朝鮮大學校 附設 醫學硏究所 1998 The Medical Journal of Chosun University Vol.23 No.1

연구 배경 : 고혈당성에 의한 산화환원반응 이상(가저산소증)이 조절 되지않는 당뇨병의 특징으로 혈관과 신경 기능에 대한 진성 저산소증의 효과와 유사하며, 당뇨 합병증의 병태생리에 중요한 역할을 한다. 고혈당이 있는 인슐린 비의존형 당뇨병 환자에서 인슐린 수준이 정상이듯이, 빈혈이 있는 당뇨병 환자에서 EPO의 농도는 실제 혈색소 농도의 감소비율과 차이가 있을 것이라 추측된다. Friedman 등은 당뇨병성 합병증 원인 인자로 가저산소증(pseudohypoxia) 또는 저산소증(hypoxia)을 제기하였고 이런 인자들이 EPO의 상대적 또는 절대적 결핍에 의한 것임을 보고하였다. 방법 : EPO-Trac^(TM 125)I RIA kit을 이용하여 방사면역측정법으로 EPO 수준을 검사하였다. 전혈 3㎖을 5-10㎖ 시험관에 정맥 채혈하였으며, 용혈과 장기간의 보존을 위하여 원심분리를 즉시 시행하여 혈청을 영하 200C에서 냉동 보관 후 일괄적으로 검사 결과를 얻었다. 결과 : 1996년 9월부터 1997년 2월까지 조선대학교 부속병원 내과에 입원한 2형 당뇨병 환자 63례를 대상으로 하여 다음과 같은 결과를 얻었다. 1) 당뇨병성 합병증이 없는 군과 있는 군간의 혈색소, 혈중 EPO농도의 차이는 유의한 차이가 있었으며 혈색소의 감소율보다 혈중 EPO의 감소율이 더 높았다. 2) 당뇨병성 망막증의 유무에 따른 혈색소 농도의 차이는 유의한 차이가 없었으나 혈중 EPO농도는 유의한 차이가 있었다. 증식성군에서만 혈중 EPO의 감소비율이 혈색소에 비해 높았다. 3) 당뇨병성 신증의 유무에 따른 혈색소, 혈중 EPO농도는 유의한 차이가 있었고 혈색소 감소율에 비해 EPO농도의 감소율이 높았다. 신증의 중증도에 따른 혈색소, EPO의 차이는 미세알부민뇨군을 제외하고는 유의한 차이를 보였고 혈색소 감소율에 비해 EPO의 감소율이 더높았다. 4) 당뇨병성 신경병증의 유무에 따른 혈색소 농도의 차이는 유의한 차이가 없었으며 EPO농도는 유의한 차이를 보였다. 혈색소와 EPO의 감소비율은 비슷하였다. 신경병증의 중등도에 따른 혈색소와 EPO농도의 변화는 유의한 차이가 없었으나 stage 3에서는 혈색소감소율보다 EPO감소율이 더높았다. 결론 : 당뇨병성 합병증을 가진 환자에서 빈혈의 정도는 대부분 혈청 EPO치의 절대적 감소에 의함을 간접적으로 밝혀낼 수 있었으며 차후 더 많은 대상으로 비교 분석이 필요하리라 사료된다. Background: Hyperglycemic-induced redox(pseudohypoxia) imbalance is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural functions and plays an important role on the pathogenesis of diabetic complications. As is true for apparently "normal" insulin levels typically found in NIDDM even in the presence of hyperglycemia, a "normal" erythropoietin level in an anemic diabetic subject may be disproportionally low for the actual red cell mass. Therefore, Friedman et al suggested that pseudohypoxia or hypoxia as an etiological factor of diabetic complications are due to absolute or relative erythropoietin deficiency Method: EPO-TracTM 125I RIA kit was used for the quantitative determination of erythropoietin(EPO) in serum by radioimmunoassay. An adequate sample of blood (3ml whole blood) was collected aseptically by venipuncture in a 5~10ml glass tube to yield a minimum of 400 L of serum per assay. The serum was promptly removed from the clot by centrifugation in order to avoid hemolysis. Then to increase its storage time it was frozen at -200C in a nonself defrosting freezer. Finally, tests were undertaken simultaneously Results We studied 63 cases with diabetes mellitus, who were admitted to Chosun University Hospital from September, 1996 to February, 1997 at the Department of Internal Medicine. We defined the control group, as diabetic patients who did not have anemia(<13mg/dl), diabetic complications(retinopathy, nephropathy, neuropathy) and the remainders were defined as the experimental group(we excluded anemic patients, who had secondary causes of anemia and diabetic patients with end stage renal disease)Data were as follow 1) The relationship of Hb and the 24hr urine protein between diabetic patients with and without complications significantly differed(p=0.02, < 0.001 respectively), but the Hb level was poorly related between diabetic patients with and without retinopathy(except in preproliferative, proliferative subgroups) and neuropathy. 2) Subgroups of patients with diabetic complications had higher 24hr urine protein than patients without diabetic complications, except stage I diabetic neuropathy 3) The EPO level was significantly different between diabetic patients with and without complications. 4) The correlation between EPO and Hb was significantly different, especially in diabetic patients with retinopathy and nephropathy according to severity of diabetic complications, compared with patients who did not have diabetic complications such as retinopathy and nephropathy. Conclusion: We know that anemia induced by diabetic complications is due to relative EPO deficiency than absolute EPO deficiency, and further evaluation and studies are needed on many cases in the future

개에서 발생한 폐수종의 치료 증례

김유수,심재현,김건우,김지용,이병희,송근호,이영원,김덕환 충남대학교 수의과대학 동물의과학연구소 2004 動物醫科學硏究誌 Vol.12 No.-

A 9 months intact male American bull dog with chief complaints of dry cough, dyspnea and fever was referred to the Veterinary Teaching Hospital, Chungnam National University. Based on the findings of physical examination, radiological examination, and blood and blood chemical examinations, the present patient was diagnosed into pulmonary edema secondary to primary bacterial and aspiration pneumonia. The patient was hospitalized and treated with buscopan, cephazolin and furosemide for 1 week. His activity and appetite was returned to normal and thoracic radiographs revealed that Jung was recovered to the normal condition after treatment for 7 days. The present patient was a case with pulmonary edema showed favorable therapeutic responses to proper medication.

당뇨병성 합병증을 가진 환자에서 혈증 Erythropoietin 농도

김동규,유기동,허광식,김상용,윤성호,조영신,권용은,김태원,김건영,정종훈,배학연 조선의대 1998 The Medical Journal of Chosun University Vol.23 No.1

역전지붕형 녹화옥상시스템 개발 방향에 관한 연구

김현수,이건호 대한건축학회 2004 대한건축학회논문집 Vol.20 No.12

The research of Green roof system began from 1995 completely, and it has been developed since the beginning of 2000 The contents of research contained the thermal conductivity, the runoff-reduction or the treated rainwater- quality of green roof system and so on But the application was limited in the existing buildings In 2003, for the first time, the green roof system was actually applicable difficulty in a new apartment from the initial design stage of a building In the future, the green roof system would occupy a fixed position on the new building For the reason of this, the prototype for green roof is necessary, which is suitable on the korean spot as well as on the korean climate So the purpose of tins study is to find out a method which improve the prototype of the korean green roof system Especially it is important to find a prototype of a improved IRMA, well known as Insulated Roof Membrane Assembly, with a few elements Thanks to the simple construction, the reduction of working-terms and the economical benefits, the IRMA could take a place slowly in the spot Two methods were used in order to achieve the purpose of research, Analysis of the existing research result and Performance analysis which a system requires And the GRS prototype of Korea was shown through the research result and comparison concerning IRMA of Germany

WIND ENERGY POTENTIAL ASSESMENT and SITING a WIND FARM in CHEJU ISLAND

김건훈,조경호,고장권,허종철,고경남 濟州大學校 工科大學 産業技術硏究所 1997 尖端技術硏究所論文集 Vol.8 No.2

본 연구는 제주도내 풍력발전기 보급 및 적지선정을 검토하는데 그 목적을 두었다. 이를 위하여 제주도내 다풍지역으로 예상되는 3개지역을 선정하여 1년간 풍력자원조사를 행하였고, 계측된 자료는 통계분석으로 풍력자원을 정량화하였으며 또한 세계적으로 경제성이 인증된 600kW 풍력발전기를 모델로하여 가상 출력을 산출함으로서 최적 풍력단지를 제시하였다. The possibility in the practical use and supply of the wind turbine in Cheju island was investigated. The wind data measured in three regions which have a plenty wind energy potential were utilized to quantify the wind power resources by statistical analysis. Power output was calculated for 600 kW wind turbine. The coastal area of Guja was superior to Daejung and Hoichun in wind power energy densities. The calculated capacity factor of 600 kW wind turbine in this site was high as much as 30%. Hoichun site, the intermediate region between the Halla mountain and the sea, was rich in wind power energy resources in winter. Hourly ideal energy density at three regions increased at sunrise, reached the maximum at 13-16 O'clock, decreased steadily, and finally remained constant at sunset.

반도체 레이저의 이득곡선에서의 비포물선형 효과

김동철,유건호 慶熙大學校 레이저 工學硏究所 1997 레이저공학 Vol.8 No.-

Use of one-band model in the calculation of gain of semiconductor lasers is convenient because it is easy to understand and takes less time to implement. However, it gives an error in the gain by neglecting the nonparabolicity. In this paper, we study the limit of the one-band model by comparing the gain calculated by the one-band model with that by a multiband model. We find that, if the active layer is bulk, the peak gain by the one-band model is approximately same as that by a multiband model. However, if the active layer is a quantum well, the peak gain by the one-band model is much larger, and the one-band model may not be used for a quantitative analysis.

Apatite-Wollastonite Glass-Ceramics 材料開發 및 치면열구전색재로의 이용을 위한 동물실험 연구

金龍成,申承澈,金豪健,申建澈,小久保正 단국대학교 치의학연구소 1991 논문집 Vol.3 No.-

The authors has experimented with Apatite - Wollastonite - Glass -Ceramic of MgO-CaO-SiO_2-P_2O_5-CaF_2 as biomaterials in order to find out the possibility for use of pit & fissure sealants. 2-rabbits would be selected with insertion of AWGC powder at lower anterior teeth after flap operation. X-ray taking has been done after 2 weeks and 4 weeks breedings. Extracted tooth had been used as samples for SEM observation after sacrificing every 2 weeks. Every samples had been observed at material portion as well as tooth. Such components as Si, Ca and P had been checked by use of EDX and compared the periodic changing data. The obtained results are as follows; 1. Apatite - Wollastonite glass ceramics were prepared with the component of MgO-CaO-SiO_2-P_2O_5-CaF_2 successfully. 2. On intraoral X-ray findings for teeth, A-W materials had been shown the slightly absorption at 2 weeks breeding sample and A-W material had been remove out by attrition otherwise it had been shown the generally radiolucent area as decalcification at 4 weeks breeding sample. 3. On SEM finding for tooth sample after insertion of A-W, the band like intermadiate zone had been found more remarkably at 2nd and 4th week breeding samples, rather than that of the sample which prepared at right after insertion. And this band zone had been fingured diffuse image by gradual. 4. Si and P might be drawn out from A-W material by disolution of A-W through the time, and it was estimated that calcium phosphate as apatite crystal, newly formed biomaterial, would be made of P component from A-W and Ca component from Tooth. 5. It was estimated that A-W material would be more useful at bone than at teeth and adaptable cement should be needed between tooth surface and A-W in case of using for pit & fissure sealant. So more studies for developing the adaptable cement would be needed.