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>

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]

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.

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.

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

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.

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.

응급의료센터에서 신경색의 조기진단

최경호,오동렬,이원재,박규남,박승현,황두영,김형국,정시경,김영민,김세경 大韓應急醫學會 1998 대한응급의학회지 Vol.9 No.4

To evaluate appropriate diagnostic studies for renal infartion in emergency medical center, we analysed 33 patients of renal infarction treated in this hospital for last 8 years. Eleven patients, 4 trauma associated and 7 aortic disease associated patients were excluded. They are 11 males and 11 females with a mean age of 51 years. Fourteen came to the emergency medical center and seven came to the outpatient department, in the other one patient renal infarction was developed during hospitalization with other disease. On their past history they had hypertension in 9, valvular heart disease in 5, and diabetic mellitus in 4 patients. Abdominal or flank pain was noted in 17 of 22(77%). The other symptoms were vomiting, nausea, fever and so on. On microscopic examination of initial urine in hospital, 5 patients showed more than 10 red blood cells by high power field examination. The mean lactic dehydrogenase level was 1,239 I.U/L(normal range 218-472 I.U/L), while the mean aspartate aminotransferase and mean alanine aminotransferase were 51 I.U/L(normal range 13-36 I.U/L) and 44 I.U/L(normal range 5-33 I.U/L). Abdominal ultrasonography showed positive findings in 5 of 16(31%), of which 3 were confirmed by Doppler ultrasonography. In 18, computed tomography was done and all those showed positive findings of renal infarction(100%). In conclusion, it is important that identify the elevated lactic dehdrogenase level in case of any suspicion about renal infarction and confirm by computed tomography.

교정 치료 후 교합력, 교합면적의 변화

최윤정,정주령,김경호 대한치과교정학회 2010 대한치과교정학회지 Vol.40 No.3

고정식 교정장치를 이용한 교정치료 후 교합의 기능적 변화를 평가하기 위해, 교합력 및 교합접촉면적을 측정하여 단기적인 변화 양상을 확인하고 소구치 발치 여부에 따른 차이를 파악하였다. 고정식 교정장치로 치료를 종료한 18세에서 40세 사이의 성인을 남자군과 여자군으로 분류하고, 각각의 군을 4개의 소구치를 발치한 군과 비발치로 치료한 군으로 세부 분류하였다(남자발치군 16명, 남자비발치군 18명, 여자발치군 19명, 여자비발치군 21명). Dental prescale system (Fuji Film Corp., Tokyo, Japan)의 pressure sensitive sheet를 5초간 최대교두감합위에서 최대근력으로 교합하도록 한 뒤 CCD camera를 이용해 교합력과 교합면적을 측정하였다. 고정식 교정장치를 제거하고 고정식 유지장치를 붙인 직후, 교정장치 제거 1주일, 1개월, 3개월, 6개월, 1년 뒤에 각각 측정하여 비교하였다. 모든 군에서 교정장치 제거 후 1년간의 유지기간 동안 교합력과 교합면적은 점진적으로 증가하였다 (p < 0.05). 모든 측정 시기에서 남자군은 여자군보다 높은 교합력과 교합면적을 보였으며 (p < 0.05), 남자, 여자군 모두에서 발치군과 비발치군 사이에는 교합력 및 교합면적에서 통계적으로 유의한 차이가 관찰되지 않았다 (p > 0.05). 본 연구를 통해 교정치료 후 1년간의 유지기간 동안 교합이 기능적으로 향상됨을 파악하였고, 소구치 발치로 인한 교합의 기능적 저하는 없을 것이라 추측할 수 있었다. Objective: This study was performed to evaluate functional changes of occlusion after orthodontic treatment by measuring the occlusal force (OcFr) and occlusal contact area (OcAr), and to compare OcFr and OcAr change according to premolar extractions. Methods: Data were obtained from 74 patients who had finished orthodontic treatment using fixed appliance aged between 18 and 40 years. Subjects were divided into groups who had four premolars extractions or non-extraction (Male extraction-16, Male nonextraction-18, Female extraction-19, Female nonextraction-21). All subjects were asked to bite pressure-sensitive sheets into maximum intercuspation with maximum bite force, and OcFr and OcAr were evaluated by measuring the sheet with a CCD camera. Records were taken right after debonding, 1 week, 1 month, 3 months, 6 months and 1 year after debonding. Results: OcFr and OcAr increased gradually in all groups during the 1 year retention period (p < 0.05). Male groups showed higher OcFr and OcAr than female groups throughout the retention periods (p < 0.05). There were no statistically significant differences of OcFr and OcAr between extraction and non-extraction groups in both males and females (p > 0.05). Conclusions: Occlusion was improved functionally throughout the 1 year retention, and premolar extraction did not induce a decline in the functional aspect of occlusion.

五加皮의 效能에 대한 硏究

최민호,이계복,조규원,박진영,김경수,송정석,한종현 한국전통의학연구소 2003 한국전통의학지 Vol.13 No.1

The purpose of this study is to measure the changes of regional cerebral blood flow (rCBF) and blood pressure (BP) of Cortex Acanthopanacis in rats, and to determine the effect of Cortex Acanthopanacis on phenylephrine (PE) induced contraction of isolated rat thoracic aorts. The measurement was continually monitored by laser-doppler flowmeter (Transonic Instrument, USA) and pressure transducer (Grass, USA) in anesthetized adult Sprague-Dawley rats through the data acquisition system composed of MacLab and Macintosh computer. Contractile force was measured with force displacement transducer under 1.5 g loading tension. The result of this experiment was as following; 1. Cortex Acanthopanacis did not effect the changes of rCBF and blood pressure significantly. 2. Contractions evoked by phenylephrine were decreased significantly by Cortex Acanthopanacis 3. L-NNA, ODQ, atropine and indomethacin significantly altered the relaxation of Cortex Acanthopanacis. 4. Propranolol did not change the relaxation of Cortex Acanthopanacis. These results indicate that Cortex Acanthopanacis did not change the rCBF and BP, but Cortex Acanthopanacis can relax PE induced contraction of isolated rat thoracic aorta and that this increasing contraction related to endothelium and various mechanism.