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>

Role of Pyruvate Dehydrogenase Kinase 4 in Regulation of Blood Glucose Levels

Jeoung, Nam Ho,Harris, Robert A. Korean Diabetes Association 2010 Korean diabetes journal Vol.34 No.5

<P>In the well-fed state a relatively high activity of the pyruvate dehydrogenase complex (PDC) reduces blood glucose levels by directing the carbon of pyruvate into the citric acid cycle. In the fasted state a relatively low activity of the PDC helps maintain blood glucose levels by conserving pyruvate and other three carbon compounds for gluconeogenesis. The relative activities of the pyruvate dehydrogenase kinases (PDKs) and the opposing pyruvate dehydrogenase phosphatases determine the activity of PDC in the fed and fasted states. Up regulation of PDK4 is largely responsible for inactivation of PDC in the fasted state. PDK4 knockout mice have lower fasting blood glucose levels than wild type mice, proving that up regulation of PDK4 is important for normal glucose homeostasis. In type 2 diabetes, up regulation of PDK4 also inactivates PDC, which promotes gluconeogenesis and thereby contributes to the hyperglycemia characteristic of this disease. When fed a high fat diet, wild type mice develop fasting hyperglycemia but PDK4 knockout mice remain euglycemic, proving that up regulation of PDK4 contributes to hyperglycemia in diabetes. These finding suggest PDK4 inhibitors might prove useful in the treatment of type 2 diabetes.</P>

Fasting induces ketoacidosis and hypothermia in PDHK2/PDHK4-double-knockout mice.

Jeoung, Nam Ho,Rahimi, Yasmeen,Wu, Pengfei,Lee, W N Paul,Harris, Robert A Biochemical Society 2012 The Biochemical journal Vol.443 No.3

<P>The importance of PDHK (pyruvate dehydrogenase kinase) 2 and 4 in regulation of the PDH complex (pyruvate dehydrogenase complex) was assessed in single- and double-knockout mice. PDHK2 deficiency caused higher PDH complex activity and lower blood glucose levels in the fed, but not the fasted, state. PDHK4 deficiency caused similar effects, but only after fasting. Double deficiency intensified these effects in both the fed and fasted states. PDHK2 deficiency had no effect on glucose tolerance, PDHK4 deficiency produced only a modest effect, but double deficiency caused a marked improvement and also induced lower insulin levels and increased insulin sensitivity. In spite of these beneficial effects, the double-knockout mice were more sensitive than wild-type and single-knockout mice to long-term fasting, succumbing to hypoglycaemia, ketoacidosis and hypothermia. Stable isotope flux analysis indicated that hypoglycaemia was due to a reduced rate of gluconeogenesis and that slightly more glucose was converted into ketone bodies in the double-knockout mice. The findings establish that PDHK2 is more important in the fed state, PDHK4 is more important in the fasted state, and survival during long-term fasting depends upon regulation of the PDH complex by both PDHK2 and PDHK4.</P>

Reaction of HDL-Bound Cholesteryl Ester Transfer Protein and a New Method for Its Activity Measurement

Jeoung,Nam-Ho,Choi,Myung-Sook,Kim,Hong-Seok,Park,Yong Bok 國立 昌原大學校 基礎科學硏究所 1993 基礎科學硏究所論文集 Vol.4 No.-

간편하고 신뢰성이 높은 CE transfer activity 측정법을 개발하려는 시도에서 정제된 혈장 HDL과 합성된 HDL(RHDL)을 CE donor로써 사용하였다. 혈장 HDL은 높은 CETP활성을 보여 정제된 혈장 HDL은 HDL/CETP complex로 이루어졌다는 것을 알 수 있었다. 이 CETP는 lipoprotein들 간의 CE교환과 순이동을 촉매했으며 순이동 현상은 HDL로부터 lower density lipoprotein쪽으로 진행되었다. 그러나 본 실험에서 apolipoprotein A-Ⅰ, 인지질, 콜레스테롤, TG를 구성성분으로 하여 합성한 HDL을 agarose에 결합시켜 CE donor로 사용한 결과 지금까지 사용되어온 방법들에 비해 신뢰성이 높았고 assay 시간과 비용이 단축되었다. Cholesteryl ester (CE) transfer between lipoproteins was studied in vitro in various incubation mixtures containing isolated lipoproteins and an inhibitor of lecithin:cholesterol acyltransferase (LCAT). Isolated high-density lipoproteins (HDL) exhibited a significant amount of cholesteryl ester transfer activity. In incubations of HDL with very low-density lipoproteins (VLDL) at 37℃, decrease of free cholesterol (FC) in human VLDL was mainly associated with decrease of cholesteryl ester (CE) in HDL. In this system, FC of human VLDL was transferred to human HDL, but could not be esterified due to LCAT inhibitor resulting in an accumulation of FC in HDL fraction. However, CE in human HDL was transferred to human VLDL during the incubation. This appears to be the major mean for keeping cholesterol equilibrium between lipoproteins. Another results support that cholesteryl ester transfer protein (CETP) promotes both the exchange and net transfer of cholesterol species between lipoproteins and that the net transfer proceeds in the direction of HDL to lower density lipoproteins, which are well agreed with the previous reports. In efforts to simplify the CETP assay method, cholesteryl-[¹⁴C]-oleate in reconstituted HDL (RHDL) covalently bound to agarose beads was used as a CE donor. This simple evaluation of CE transfer activity did not require the time-consuming ultracentrifugation before and after the incubation, that has been used in the previous assay. It also eliminates the use of heparine-MnCl₂ordextran sulfate-MgCl₂for the precipitation of LDL or VLDL, that is relatively costly.

Hypocholesterolemic Effect of Naringin Associated with Hepatic Cholesterol Regulating Enzyme Changes in Rats

(Nam Ho Jeoung),(Yong Bok Park),(Myung Sook Choi),(Yong Won Shin),(Song Hae Bok),(Tae Sook Jeong),(Ki Hwan Bae),(Sung Heui Lee) 경북대학교 유전공학연구소 2000 遺傳工學硏究所報 Vol.14 No.-

Identification of Retinoic Acid Receptor Element in Human Cholesteryl Ester Transfer Protein Gene

(Nam Ho Jeoung),(Won Gu Jang),(Jung Il Nam),(Young Mi Kim Pak),(Yong Bok Park) 경북대학교 유전공학연구소 2000 遺傳工學硏究所報 Vol.14 No.-

유독성 와편모류 Alexandrium catenella에 대한 Pseudoalteromonas sp. NH-12의 살조능

정남호 ( Nam Ho Jeoung ),손홍주 ( Hong Joo Son ),정성윤 ( Seong Yun Jeong ) 한국환경농학회 2012 한국환경농학회지 Vol.31 No.2

우리나라뿐만 아니라 전 세계적으로 적조 및 마비성 패독을 일으켜 문제시되고 있는 유독성 와편모류인 A. catenella를 살조시키는 해양미생물 Pseudoalteromonas sp. NH-12를 마산만의 적조발생 해역에서 분리, 동정하고 그 특성과 살조능에 대해 연구함으로써 보다 환경 친화적인 적조 구제 기술개발의 기초 자료를 제공하고자 하였다. 적조발생 해역인 마산만의 해수에서 분리한 38개의 해양미생물 균주 중 4종의 미생물이 A. catenella에 대해 살조능을 나타내었으며, 이중 살조능이 가장 우수한 NH-12 균주를 선별하였다. 본 균주는 API kits 및 16S rRNA gene 염기서열을 분석하여 계통분류를 행한 결과 Pseudoalteromonas 속으로 분류되었으며, 최적 배양조건은 25℃, pH 8.0, 3.0% NaCl 농도였다, Pseudoalteromonas sp, NH-12의 성장 단계별 살조능은 대수증식기 후기, 정지기, 대수증식기 중기, 유도기순으로 높게 나타났다. 살조물질은 대수증식기 중기 이후에 활발히 생산되기 시작하여 대수증식기 후기에 가장 고농도로 축적되는 것으로 판단된다. 2조 배양계를 이용한 살조 유형조사에서 Pseudoalteromonas sp. NH-12는 격리된 상태에서도 A. catenella를 살조시켜 ``직접 공격형``이 아니라 세포외로 물질을 분비하여 살조시키는 ``살조인자 분비형``으로 확인되었다. 또한 NH-12 균주 배양여과액을 5% 첨가하였을 때 36시간 후에 A. catenella는 100% 살조되었고, 10%를 첨가한 경우 24시간 후에 99% 이상 살조되었다. BACKGROUND: The aim of this study was to isolate and identify algicidal bacterium that tends to kill the toxic dinoflagellate Alexandrium catenella, and to determine the algicidal activity. METHODS AND RESULTS: Among of four algicidal bacteria isolated in this study, NH-12 isolate was the strongest algicidal activity against A. catenella. NH-12 isolate was identified on the basis of biochemical characteristics and analysis of 16S rRNA gene sequences. The isolate showed 97.67% homology with Pseudoalteromonas prydzensis ACAM 620T (U85855), and was designated Pseudoalteromonas sp. NH-12. The optimal culture conditions of this isolate were 25℃, initial pH 8.0, and 3.0% (w/v) NaCl concentration. The algicidal activity of NH-12 was significantly increased to maximum value in the late of logarithmic phase of bacterial culture. As a result of ``cell culture insert`` experiment, NH-12 is assumed to produce secondary metabolites, as an indirect attacker. When 10% culture filtrate of NH-12 was applied to A. catenella, over 99% of algal cells were destroyed within 24 h. In addition, the killing effects were increased in dose and time dependent manners. CONCLUSION(S): Taken together, our results suggest that Pseudoalteromonas sp. NH-12 could be a candidate for controlling of toxic algal blooms.

노인의 차별경험인식과 자살사고간의 관계 연구

양정남(Yang, Jeoung-Nam),최은정(Choi, Eun-Jeung),이명호(Lee, Myoungh-Ho),김영(Kim, Young),김남희(Kim, Nam-Hee) 한국노인복지학회 2018 노인복지연구 Vol.73 No.3

본 연구는 노인이 인지하는 차별경험에 대한 인식과 자살사고, 사회적지지의 수준을 파악하고 노인차별이 자살사고에 미치는 영향관계에서 사회적지지의 조절효과를 검증하는데 그 목적이 있다. 이를 위해 J도과 G시, N시에 거주하는 60세 이상 노인 255명을 대상으로 설문조사를 실시하였다. 노인차별을 독립변수로, 자살사고를 종속변수로 설정하고 사회적지지의 조절효과를 실증적으로 검증하였다. 분석결과, 연구모형의 모형적합도가 양호함을 확인하였고 노인이 느끼는 차별인식이 자살사고에 정적인 상관관계를, 사회적지지와 자살사고는 부적상관관계를 보였다. 또한 노인의 사회적지지 수준이 차별인식과 자살사고에 미치는 영향관계에서 조절변수 역할을 확인하였다. 이와 같은 연구결과를 통해 노인 자살예방을 위한 기초자료를 제공하고, 노인차별인식을 개선하고 노인자살을 감소하기 위해 사회적지지 수준을 확장하기 위한 사회복지적 개입의 필요성에 대해 논의하였다. This study aimed to examine perceived discrimination of the elderly, suicidal incidents and the level of social support and to verify the moderating effect of social support on the relationship between perceived discrimination of the elderly and suicidal incidents among elderly people. To this end, a survey was conducted on 255 elderly people, aged 60 or older, residing in J Province and G City. For empirical verification, perceived discrimination of the elderly was set as an independent variable, suicidal thought as a dependent variable and social support as a moderating variable. The results of the analysis showed that the goodness of fit of the research model was appropriate. And it found that there was a positive correlation between discrimination perception of the elderly and their suicidal ideation and that there was a negative correlation between social support and suicidal ideation. The level of social support for the elderly was verified to have a moderating effect on the relationship between perceived discrimination and suicidal ideation. This study provided preliminary data for research on the prevention of elderly suicide and discussed the necessity of social welfare intervention to improve the level of social support in order to reduce perceived discrimination of the elderly and lower elderly suicide rates.

Measurement of two-photon absorption coefficient of dye molecules doped in polymer thin films based on ultrafast laser ablation

Nam, Jung Rim,Kim, Chang Ho,Jeoung, Sae Chae,Lim, Ki Soo,Kim, Hwan Myung,Jeon, Seung-Joon,Cho, Bong Rae Elsevier 2006 Chemical physics letters Vol.427 No.1

<P><B>Graphical abstract</B></P><P>Measurement of two-photon absorption coefficient of dye molecules based on fs-laser ablation threshold <I>F</I><SUB><I>th</I></SUB></P><ce:figure id='figure.0010'></ce:figure> <P><B>Abstract</B></P><P>Two-photon absorption cross-section of a series of dyes (<B>1a</B>–<B>3a</B>) in polymer thin films was determined by measuring the femtosecond laser ablation threshold. The ablation threshold decreased gradually when the dopant increased. The two-photon absorption cross-section of the dye molecules dispersed in the polymer film was estimated by using the theoretical relationship between the ablation threshold of the blended polymeric thin films and the dye concentration. The relative values of two-photon absorption cross-section are in good agreement with those measured in solution. On the other hand, the absolute values are smaller than the latter.</P>

비강 및 부비동에 발생한 점막형 악성흑색종의 임상적 특성 및 치료결과

남정권,김상윤,김용재,김재호,이봉재 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.4