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>

심근 허혈-재관류 백서 모델에서 mitogen-activated protein kinase 활성화에 대한 α-lipoic acid의 효과

김연경,박은미,최준호,윤경호,유남진,이은미,김남호,정진원,김민선,박병림,오석규 圓光大學校 醫科學硏究所 2006 圓光醫科學 Vol.21 No.1

단기간의 금연과 일회성 유산소 운동이 흡연자의 심혈관 반응에 미치는 영향

송준경(Jun Kyung·choi),최현민(Hyun Min Choi),김종경(Jong Kyung Kim),노호성(Ho Sung Nho) 한국사회체육학회 2012 한국사회체육학회지 Vol.0 No.48

The purpose of this study was to investigate cardiovascular responses to a bout of aerobic exercise and acute smoking cessation in smoker. nine collegiate male smoker who have been smoking(duration of smoking: 7.5 ± 0.9yrs; number of cigarettes per day: 15.5 ± 1.5) participated in this study. All subjects performed PEI to stimulate Group IV metaboreceptor at immediately after smoking, 24hours after smoking cessation and smoking after a bout of aerobic exercise. they were measured SBP, DBP, HR, SV, CO, TVC using by finometer(FMS co, Netherland). As a result, compared to immediately after smoking, SBP, DBP, and MAP were significantly decreased 24-hours after smoking cessation at rest and PEI(p<0.05). In addition, smoking after a bout of aerobic exercise caused by post-exercise hypotension indicated that SBP was significantly decreased compared to immediately after smoking(p<0.05). also, the changes in DBP and MAP at rest and handgrip exercise were significantly smaller compared to immediately after smoking(p<0.05). Thus, the results showed that smoking cessation during 24-hours and a bout of aerobic exercise relieve excess blood pressure response and enhanced arterial baroreflex in collegiate male smoker. It is concluded that caused exercise pressor reflex by stimulated Group IV may be effective to improve excess blood pressure responses.

N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway

( Daewoo Lee ),( Sung Ho Kook ),( Hyeok Ji ),( Seung Ah Lee ),( Ki Choon Choi ),( Kyung Yeol Lee ),( Jeong Chae Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.11

There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC. [BMB Reports 2015; 48(11): 636-641]

열공형과 비열공형 피질하 혈관성 치매에서 위험인자의 차이에 관한 비교 연구

배희준,정지향,유경호,나덕렬,김상윤,최경규,양동원,손의주,이상도,김재우,박경원,김응규,이재홍,박미영,한일우,함동석,최문성,하충건,최성혜,이애영,이병철,한설희 대한치매학회 2003 Dementia and Neurocognitive Disorders Vol.2 No.2

Backgrounds and Objectives: Vascular dementia is a group of dementing disoders arising from various stroke syndrome. Among these. subcortical ischemic vascular dementia (SIVD) is regarded as a relatively distinct clinical entity. However, MRI patterns of SIVD are not homogenous. In some patients, lacunes are dominant, and in others, subcortical white matter changes are. This study was designed to compare risk factor profiles between SIVD with and without multiple lacunes. Methods: We divided 47 subjects (22 males, mean age. 68 years) recruited from VADAPET (Multicenter Trial For Evaluation Of The Changes In the PET Images Of Subcortical Vascular Dementia Patient) study into two groups one with more than 5 lacunes in deep gray matter (lacune group) and the other with 5 or less(non-lacune group) Clinical characteristics and laboratory findings of two groups were compared. Results: Nineteen of 47 patients (40%) belonged to the lacune group. The lacune and non-lacune groups d d not differ in the following variables: age, hypertension, diabetes mellitus, hyperlipidemia heart disease, history of stroke or TIA, history of trauma or major surgery, family history of hypertension stroke, or dementia, age at diagnosis of dementia, body mass index, white blood cell count, ESR, CRP, fibrinogen, hemoglobin A1C, total cholesterol. LDL cholesterol creatinine, proteinuria, glucosuria, and microhematuria. However, male sex, smoking alcohol. hemoglobin, and HDL cholesterol were possibly associated more with lacune group SIVD than with non-lacune group (p<0 1) Multivariate analyses revealed that smoking, hemoglobin, and HDL cholesterol were independent predictors of SIVD with multiple lacunes Conclusion: Our study suggests that SIVD with multiple lacunes may be significantly different in smoking habits hemoglobin, and HDL cholesterol from SIVD without multiple lacunes.

신규 방사성 항암제 DW-166HC 의 소핵시험

문은이(Eun Yi Moon),이진(Jin Lee),이원용(Won Yong Lee),최청하(Chung Ha Choi),이덕근(Dug Keun Lee),유제만(Jei Man Ryu),정용호(Yong Ho Chung),윤성준(Sung June Yoon),박경배(Kyung Bae Park) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3

DW-166HC (^(166)Holmium (^(166)Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumorigenic spectrum, especially against human hepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous arid intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I (^(165)Ho-Chitosan complex : cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC (^(166)Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr arid 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative controi group but there was significant difference of this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.

Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

Lee, Yoo-hwan,Kim, Jung-hee,Song, Choon-ho,Jang, Kyung-jeon,kim, Cheol-hong,Kang, Ji-Sook,Choi, Yung-hyun,Yoon, Hyun-Min KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.1

Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, $H_2O_2$) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and $H_2O_2$ in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and $H_2O_2$-induced growth inhibition. Results: The results showed that EGL effectively inhibited $H_2O_2$-induced growth and the generation of ROS. EGL markedly suppressed $H_2O_2$-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 ($p-{\gamma}H2AX$), a widely used marker of DNA damage, suggesting that EGL prevented $H_2O_2$-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against $H_2O_2$-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from $H_2O_2$-induced oxidative cytotoxicity.

옥외용 고분자 전기절연재료의 내후특성

최남호,구경완 永同大學校 1997 硏究論叢 Vol.3 No.1

본 논문에서는 자외선 조사와 염무 주수 처리에 따른 전기절연재료용 폴리머의 열화특성에 대하여 연구하였다. 사용된 전기전연재료로는 EPDM, SR, PTFE, EVA와 같은 폴리머 재료들이다. 표면에서의 열화특성에 대해 알아보기 위하여 접촉각과 표면저항이 측정되었으며, SEM을 사용하여 표면형상의 변화를 관찰하였다. 뿐만아니라, EVA(고분자애자)에 대한 건조섬락전압시험과 임펄스 섬락전압시험이 이루어졌다. 이와 같은 실험을 통하여 염무와 자외선 조사와 같은 기후 요인에 대하여 폴리머의 우수한 내후성을 확인할 수 있었다. 특히 PTFE는 다른 재료에 비해 우수한 내후성을 지니는 것을 확인할 수 있었으며, 표면형상의 변화가 폴리머의 전기적 특성에 큰 영향을 미치지 못하는 것으로 확인되었다. In this paper, we investigated the aging characteristics of polymers for electrical insulation by UV radiation and salt water spray treatment. The materials of used polymers are EPDM, SR, PTFE, and EVA. To know the aging characteristics of polymer surface contact angle and surface resistance were measured and to observe the change of the suface shape SEM was used. Dry flashover voltage test and impulse flashover voltage test were carried for the polymer insulator, EVA. We concluded that (1) the polymers had a good resistance to weathering conditions like as salt spray, UV irradiation and mix of them. (2) the surface characteristics of PTFE was better than the other, and (3) electrical characteristics of the polymers was little affected by change of surface shape.

新羅의 三國統一政策과 우리의 統一安保敎育과의 函數關係 硏究

崔廉烈,閔慶浩 湖西大學校工業技術硏究所 1985 工業技術硏究所論文集 Vol.4 No.-

Korean peninsular was devided into South and North Korea by a few powers since World WarⅡ. Thought forty years have passed since then, the prospect for the peace and the unification in this peninsular is not bright now. This situation is not desirable not only for ourselves but also for the world. Recently it is often said that "Unification" reminds us of "Ideology". The aim of this thesis is to help to rightly understand the unification and the national security of this peninsualr, by studying the relationship between Silla's policy for the unification of the three kingdoms and our present education for unification and the national security. What was Silla's policy for the unification of the three kingdom? For their existence, there was only one way --- "Unification". In those days the unification had to be pursued in a specific social and historical environment, and in a special reality. And this article shows that Silla's policy for unification must be found in comparison with Mencius' political ideas. 1) The king of Hsiang of Liang asked Mencius, "How can be the whole country stabilized?" Mencius replied, "When the whole country will be unified, there will be peace in it." "Who on earth will unify it?", the king asked again. Mencius said, "I replied. He who has no pleasure in killing men can unit it." (Chapter Ⅰ, TheWWorks of Mencius) 2) The duke W???n of Ta???g asked Mencius, saying "T???ng is a small kingdom, and lies between Ch??? and Ch???. Shall I serve Ch??? or shall I serve Ch??? ?" Mencius replied, "This plan which you propose is beyond me. If you will have me counsel you, there is one thing I can suggest. Dig deeper your moats; build higher your walls; guard them as well as your people. In case of attack, be prepared to die in your defence, and have the people so that they will not leave you; This is a proper course. 3) The duke W???n of Ta???ng asked Mencius, saying "The people of Ch??? are going to fortify Hsieh. The movement occasions me great alarm. What is the proper course for me to take in the case? Mencius replied, "Formerly, when king Tai dwelt in Pin, the barbarians of the north were continually making incursions upon it. He therefore, left it, went to the foot of Mount Ch??? and there took up his residence. He did not take that situation, as having selected it. It was a matter of necessity with him. If you do good, among your descendants in after generations, there shall be one whoi will attain to the royal dignity. A price lays the foundation of the inheritance, and hands down the begining which he has made, doing what may be continued by his successors. As to the accomplishment of the great result, that is with Heaven. What is that Ch??? to you, Oh, Prince? Be strong to do good, That is all your business." 4) The duke W???n of T???ng asked Mencius, saying "T???ng is a small state. Though I do my utmost to serve those large kingdoms on either side of it, we cannot escape suffering from them. What course shall I take that we may do so?" Mencius replied, "Formerly, when King T???i dwelt in Pin, the barbarians of the north were constantly making incursions upon it. He served them with skins and silks and still he suffered from them. He served them with dogs and horses and still he suffered from them he served them pearls saying, "What the barbarians want is my territory. I have heard this -- that a ruler does not injure his people with that where-with he nourishes them. My children, why should you be troubled about having no prince? I will leave this." Accordingly, he left Pin, crossed the mountain Liang, built a town at the foot of Mount Chi, and dwelt there. The people of the Pin said, "He is a behavolent man. We must not lose him." Those who followed him looked like crowds hastening to market. On the other hand, some say, "As the kingdom is a thing to be kept from generation to generation, on e individual cannot undertake to dispose of it in his own personh. Let him be prepared to die for it. Let him not quit it." I ask you, prince, to make your selection between these two courses." 5) The King Hs???an of Ch??? asked, "Is there any way to regulate one's maintenance of intercourse with neighboring kingdoms?" Mencius replied, "There is. But it requires a perfectly virtuous prince to be able, with a great country, to serve a small one, -- as, for instance, T???ng served Ko, and King W???n served the Kw???n barbarians. And it requires a wise prince to be able, with a small country, to serve a large one,--- as the King T???i served the Hs???n-y???, and K???u-ch???en served W???. He who with a great state serves a small one, delignts in Heaven. He who with a small state serve a large one, stands in are of Heaven. He who delignts in Heaven will affect with his love and protection the whole kingdom. He who stands in awe of Heaven will affect with his love and protection his the Majesty of Heaven, and will thus preserve its favouring decree. - Adapted from Stduies in the History of Sinlla by Dr. Yasukazu Suematsu in Gakushuin University, at the request of Harvard - Yenching Institute. -

의료환경 변화에 대비한 의학기술부문의 교육방향

최종학,윤범철,조경진,이준협,임국환,고성진,최경호 高麗大學校 倂設 保健大學 保健科學硏究所 2003 保健科學論集 Vol.29 No.1

Under the pressure to open the service market as proposed by World Trade Organization, we can easily expect our educational systems for allied health professions will experience a lot of changes in near future. Accordingly, we compared our current educational systems for allied health professions with the foreign ones and mapped out some strategies predicting the forthcoming enormous changes. Major investigations and analysis are summed up as follows, The educational programs for allied health professions which was started in 1963 in Korea are stilled remained as 2 to 3 school years, while the systems in advanced countries have already been changed or been changing from 2 year to 4 year college levels. We can hardly find the uniform educational system or school years for the allied health professions in the world except for Korea. Fortunately, university level four-year programs for the profession was established in 1979 in Won-joo for the first time in Korea. However, there are still only few four-year programs in this country. To meet the rapidly changing needs we have faced in the health areas we should supply appropriate health personnel through various efforts. Now we would like to suggest followings, <Educational goals for the allied health professions> 1) reconfirming characteristics for the educational goals of health professions 2) extending school years for the allied health professions 3) strengthening clinical training and internship 4) expanding opportunities for the continuing education through lifelong education 5) upgrading from old-fashioned technologies to advanced technologies 6) cultivating competencies of health professionals for the global competition <Suggestions for the Development of Allied Health Professions> 1) reforming the school years of educational programs for the allied health professions to meet the global standards 2) expanding the role of junior college programs for the allied health professions through the development of intensive courses in the professions. 3) diversifying and specializing the allied health professions mainly through 4 year B.S. degree programs.