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>

ORiginal Article : Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

( Yoon Jeong Choi ),( Nayoung Kim ),( Ju Yup Lee ),( Ryoung Hee Nam ),( Ji Hyung Seo ),( Seonmin Lee ),( Hee Jin Kim ),( Yoon Jin Choi ),( Hye Seung Lee ),( Dong Ho Lee ) 대한간학회 2016 Gut and Liver Vol.10 No.3

Background/Aims: This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-Lcysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. Methods: Sprague- Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanolonly group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor a, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. Results: PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMKS005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. Conclusions: These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes. (Gut Liver 2016;10:348- 355)

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.

7두의 개에서 배설성 요로조영술을 통한 신장 기능 평가

최윤정,이기자,최형준,이용진,박성준,송근호,정성목,최호정,이영원 忠南大學校 獸醫科大學 動物醫科學硏究所 2005 動物醫科學硏究誌 Vol.13 No.-

Excretory urography is a type of contrast study used to verify and localize upper urinary tract disease. It is an inexpensive and easy way to visualize of anatomic and functional status of the kidney and has been used as a primary imaging modality for the evaluation of urinary tract abnormalities. We describe urological signs of 7 dogs who examined with excretory urography and ultrasonography. Six cases were referred to veterinary medical teaching hospital. Chungnam national university (VMTH, CNU) to evaluate renal function after the treatment for renal failure and one case was referred showing hematuria. In case 1, 2 and 4, blood test and urinalysis was normal and the results of excretory urography presented that renal function were normal range. In case 3, the results of urinalysis, ultrasonography, and excretory urography except blood test presented abnormal kidney and hydronephrosis was diagnosed. In case 5 and 6, blood test, urinalysis, ultrasonography and excretory urography indicated renal failure. In case 7, blood test, urinalysis and ultrasonography presented partially abnormal signs, however, the results of excretory urography was normal range.

Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

Choi, Eun Sik,Lee, Yun Jung,Seo, Chang Seob,Yoon, Jung Joo,Han, Byung Hyuk,Park, Min Cheol,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2016 Evidence-based Complementary and Alternative Medic Vol.2016 No.-

<P>Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-<I>κ</I>B) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-<I>κ</I>B and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-<I>κ</I>B was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-<I>κ</I>B translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-<I>α</I> in HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug.</P>

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.

세종기지 주변 남극지역에 형성된 빙하의 재료특성과 결정구조

최경식,윤호일 韓國海洋大學校 附設 海洋科學技術硏究所 1994 硏究論文集 Vol.3 No.-

남극지역에 형성된 육성빙(land-based ice)인 빙하와 그로 부터 분리된 해상의 유빙에 대한 현장 조사와 실험을 통하여 남극빙하 얼음의 재료특성과 결정 구조에 대한 기초자료를 수집하였다. 이를 위하여 본 연구에서는 남극 세종기지 주변에 형성된 빙하얼음과 해상의 유빙 그리고 육상에서 채취한 얼음의 시료로 부터 실험실 분석을 통해 얼음의 밀도와 공기함유량을 조사하였고 또한 현미경 관찰을 통해 얼음의 결정구조의 형태와 결정크기를 조사하였다. Basic information on the mechanical properties and crystallographic structures of Antarctic land-base ice is obtained from field survey and laboratory experiments at Korean King Sejong Station, Antarctica. In this study several ice samples are collected from the top layers of glacial ice, the icebergs stranded on the beach and from the first-year lake ice to compare their densities and air contents volume inside ice samples. The ice samples are also prepared to investigate their grain sizes and crystal formation patterns.

농부가 아닌 환자에서 발생한 긴털가루진드기(Tyrophagus Putrescentiae)에 의한 기관지천식 1례

최대로,김형수,고창옥,김희선,윤호성,박용범,김상훈,이재영 대한천식 및 알레르기학회 2004 천식 및 알레르기 Vol.24 No.1

Storage mites are believed one of the most important allergens in farmers and rural regions. Tyrophagus putrescenitiae, belonging to storage mites, is found not only within storehouses but also in the house dust, and the third most common mites following Dematophagoides farinae and Dermatophagoides pteronyssnus in house dust in Korea. The sensitization rate to Trophagus putrescentiae was reported as high as that of house dust mite in patients visiting the allergy clinic in large cities in Korea. We experienced a 69-year-old man who had suffered from dyspnea, wheezing, and coughing for 10 years. He retired from the teaching profession, and had lived in a large city. Deajeon. The skin prick test showed a positive reaction to Tyrophagus putrescentiae and negative reactions to house dust mites. The bronchial challenge test with Tyrophagus putrescentiae showed late asthmatic reaction. We confirmed a Tyrophagus putrescentiae induced asthma in non occupational setting. (J Asthma Allergy Clin Immunol 24 : 141-5, 2004)

운동 부하 후 혈액 성분의 변화에 관한 연구

최윤택,최상호 경남대학교 교육문제연구소 2001 敎育理論과 實踐 Vol.11 No.1

The purpose of this study is to investigate the changes of the constituents in the blood after the exercise by blood analysis. Subjects consist of 5 athletes and 5 non-athlets, who are the students of Kyung-buk national university. The blood of each subject was collected three times -at rest ; shortly after the 7-minutes - bicycle ergometer ride with gradual loading ; 10minutes after the end of the exercise. The results of the experiments are as follows 1.Red Blood Cell of the athlete group increased from 4.69×106개/mm3 at rest to 5.20×106개/ mm3 shortly after the exercise and to 5.04×106개/mm3 10 minutes after the end of the exercise. Red Blood Cell of the non-athlete group increased from 6.50×103개/mm3 at rest to 10.40×103개/mm3 shortly after the exercise and to 9.70×103개/mm3 10 minutes after the end of the exercise. White Blood Cell of the non-athlete group increased from 7.38×106개/mm3 at rest to 11.40×106개/mm3 shortly after the exercise and to 10 minutes after the end of the exercise.There was not significant difference between athlete group and non-athlete group. 3.Hemoglobin of the athlete group increased from 15.68 g/dl at rest to 17.14g/dl shortly after the exercise and to 16.22 g/dl 10-minutes after the end of the exercise. Hemoglobin of the non-athlete group also increased form 15.18 g/dl이 at rest to 16.28 g/dl shortly after the exercise and to 15.18 g/dl 10minutes after the end of the exercise. There was not significant difference between athlete group and non-athlete group. 4.Hematocrit of the athlete group increased from 45.42% at test to 48.60% shortly after the exercise and to 45.62% 10minutes after the end of the exercise. Hematocrit of the non-athlete group also increased from 42.52% at rest to 46.64% shortly after the exercise and to 44.44% 10minutes after the end of the exercise. there was not significant difference between athlete group and non-athlete group. 5.Blood Sugar of the athlete group increased from 77.18 mg at rest to 78.46mg shortly after the exercise and to 79.52 mg 10minutes after the end of the exercise. Blood Sugar of the non-athlete group also increased from 84.40 mg at rest to 89.16 mg shortly after the exercise and to 89.32 mg 10minutes after the end of the exercise. There was not significant difference between athlete group and non-athlete group.

가막만에 분포하는 대형저서동물의 계절적 분포 및 출현

최상덕,문성용,안치영,윤호섭,정형택,이삼노,서호영 國立 麗水大學校 환경문제硏究所 2001 環境硏究論文集 Vol.4 No.-

This study was coducted to describe the distribution and appearance pattern of macrobenthos in Kamak Bay, the southern coastal of Korea. Sampling was perfound seasonally using Van Veen grab(0.1㎡) from April 2001 to December 2001. A total of 22 macrobenthic species occured: Bivalvia accounted for 12 species(55%), and Mollusca 5 species(23%). The mean density of macrobenthos was 153.9ind./㎡, a major dominant species were a Bivalvia, Paphia undulata(28.3ind./㎡), and a Cirripedia, Chthamalus challengeri(5ind./㎡), which frequency occur in the costral area. These species showed very low density at station 1 in the Kamak Bay.