Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

Yun Ho Jo,Hwan Lee,Myeong Hwan Oh,Gyeong Hee Lee,You Jin Lee,Ji Sun Lee,Min Jung Kim,Won Yong Kim,Jin Seong Kim,Dae Seok Yoo,Sang Won Cho,Seon Woo Cha,Mi Kyung Pyo 한국영양학회 2020 Nutrition Research and Practice Vol.14 No.4

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson"s trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

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

고혈압 환자들의 건강행태

김석범,강복수,윤성호,황정희,이경수 韓國保健敎育.健康增進學會 2000 보건교육건강증진학회지 Vol.17 No.1

This study was conducted to examine health behaviors in hypertensive patients and the factors that would affect these healthy life-styles, and to provide basic data for effective and continuous hypertension control in private medical facilities. Among those patients diagnosed as hypertension who had visited the Department of Internal Medicine of Yeungnam University Hospital during the two month period from August 2 to September 30, 1999, the present study included 222 patients who were in more than one month after the initial diagnosis of hypertension and those who had hypertension for less than 10 years. Using a structured questionnaire, the present study was conducted by a self-administered survey method, and the obtained data were analyzed with t-test, χ2-test and one-way analysis of variance using the SPSS statistical program. The scores on knowledge related to hypertension were higher as the education level of a patient was higher(p〈0.05). As for occupation, those who performed office or management jobs showed higher scores than those who were into manufacturing jobs, and as for economic status, although those patients who were in middle class showed highest scores, however, no statistical significance was observed. The scores of knowledge on hypertension was higher when the family history hypertension was present(p〈0.05). The scores of health-related behaviors were higher with higher education level and higher economic status, higher in those with family history of hypertension, and higher in those with office or management jobs than those who had manufacturing jobs(p〈0.05). Blood pressure measurement on regular basis was performed most frequently in those who were between 50∼59 years old with 83.3% and was least frequent in those who were older than 70 years old with 50%(p〈0.05). The frequency of regular blood pressure measurement was higher with higher education level, higher economic status, higher in those with family history of hypertension, and the highest in those with management position with 93.5%, however, on statistical significance was observed. Changes in health-relaxed behaviors after hypertension diagnosis were higher with higher education level, higher economic status, and in those patients performed office or management work. In particular, diet change was observed in female and higher economic status and smoking cessation was observed in 60∼69 years old. Housewives and office workers or managers have taken exercise more regularly and those who had management jobs and had high scores on knowledge related to hypertension would participate health education program more actively. Thus, for improving health-related behaviors for continuous management of hypertension, changes in health-related behaviors can be followed through conduction health education to improve understanding of knowledge related to hypertension as the method of helping to improve changes in health life-styles in those with little education and those in low economic status.

급성 뇌경색 환자에서 경색 위치가 심근 효소치 상승에 미치는 영향

윤경호,박현영,박성욱,장혁,김요식,조광호,유남진,김남호,오석규,정진원 圓光大學校 醫科學硏究所 2003 圓光醫科學 Vol.18 No.2

수냉쿨러의 냉각 효율 향상을 위한 플레이트 부품의 형상에 관한 연구

성윤호,김형찬,김선민,윤석영,이영웅,이상욱 순천향대학교 부설 산업기술연구소 2021 순천향 산업기술연구소논문집 Vol.27 No.2

This study investigates changes in cooling efficiency for heat sink plate width, perforated width, and chamfer angle as part of a parameter study to maximize cooling efficiency of heat sink by setting various variables on plates. The width of the plate is set to 16, 20, 24, 28 mm, perforated width 1.5, 2.0, 2.5 mm, chamfer angles 5, 10, 15 and 20°. By conducting a computational study with Ansys Fluent, the sink plate with plate width of 16mm, perforated width of 3mm and chamfer angle of 10° is shown to be the best cooling efficiency.

ETACS와 CDMA 디지털 셀룰라 시스템이 공존하는 환경에서 Interference Canceller System의 설계 및 구현

장원호,홍주석,이윤현 한국항행학회 2002 韓國航行學會論文誌 Vol.6 No.4

본 논문에서는 인접한 대역에 ETACS와 CDMA 방식의 디지털 셀룰라 시스템이 공존하는 중국 상해 지역의 간섭환경에서 기존의 간섭제거장비보다 이를 효과적으로 개선할 수 있는 Interference Canceller Systern(ICS)을 설계하고, 개발된 부품들을 통해 구현하였다. 구현된 ICS는 무선 채널환경의 변화에 안정적이면서 인접한 대역의 ETACS와 CDMA방식의 디지털 셀룰라 시스템 간에 약 29dB이상의 간섭 제거 성능을 보유한 시스템임을 확인하였다. In this paper, we provide the Interference Canceller Systems(ICS) in the wireless environments in the presence of co-existing ETACS and CDMA digital cellular systems to effectively cancel the interference than the established canceller systems. We proved the enhanced cancelling performances more than 29 dB cancellation characteristics between co-existing ETACS and CDMA digital cellular systems and the stabilized system characteristics in the rapidly changing wireless circumstances.

Cytokinin류의 경엽처리가 봄감자 동화물질 전류에 미치는 영향

蔡潤錫,姜鎬宗 진주산업대학교 2001 論文集 Vol.40 No.-

Effect of Cytokinins(Kinetin and Benzyl adenin :BA) on the yields and carbohydrats and nitrogen compounds in the different parts of the spring potatoes as Stadies. Both kinetin and BA caused sisnifican (P <0.05) increare in yields, (carbohydrats and nitrogen compounds in the plant) while no sisnificar increares were observed in treatments the average tubes weights per plant were increased incread in low concentration of kinetin treatment where are in hight concentration of BA. Starch conteints in leaf treated with kinetin and BA showed lower than that of the control, and in stem 1∼2% higher than that of the control the starch con in treat the control. The starch sugar contents in the tuber treated with kinetins and BA has no significan difference between the treatment and the control. The free sugar contents in the leaf, freated with kinetins showed me much significan differentes between the treatment and the control.

J-R 곡선에 대한 시편크기의 영향에 관한 연구

조연제,석창성,김영진,양원호,최용식 成均館大學校 科學技術硏究所 1995 論文集 Vol.46 No.1

The objective of this paper is to investigate the constraint effect on fracture resistance curves. A series of fracture toughness tests with different specimen sizes taken from nuclear piping materials(SA312 TP347 SA516 Gr. 70) were performed. Test results show that fracture toughness is increased with increase in specimen size, probably due to the relaxation crack tip constraint. Elastic-plastic finite element analyses were also performed to investigate the constraint effect. Numerical results show that the stress triaxiality at the crack tip is the governing factor for fracture toughness.

수박종자의 크기가 묘의 소질 및 수량에 미치는 영향

강호종,채윤석,이상우,문국이 진주산업대학교 농업기술연구소 2007 農業技術硏究所報 Vol.20 No.-

수박종자의 크기에 따른 발아율과 배축 굵기, 뿌리발육상태, 접목묘 생육 및 과실 품질에 미치는 영향에 대한 연구결과를 요약하면 다음과 같다. 1. 종자 크기별 발아율은 대립은 97%, 중립은 94%, 소립은 91.9%로 종자의 중량이 큰 대립종자 일수록 발아율이 높았다. 2. 종자의 크기별 배축 굵기는 대립이 1.63mm, 중립이 1.45mm, 소립이 1.29mm로 종자의 중량이 클수록 배축이 굵고 뿌리무게도 무거운 것으로 나타났다. 3. 종자의 크기별 접수의 소질은 종자의 중량이 큰 것일수록 좋은 경향이 있었으나 초장, 엽장 등은 소립종자에서 유의적인 경향이 나타났다. 4. 종자의 크기별 접목묘 소질은 대립종자에서 유의적인 차이를 보였고, 뿌리중량은 중립종자에서 다소 높은 경향이었으나 통계적 유의성은 인정되지 않았다. 5. 종자 크기별 착과 절위별로 과중은 자만 7~8절에서 6.6kg, 자만 9~ 10절에서 7.4kg, 자만 11~13절에서 7.2kg으로 자만 9~10절에 착과시킨 처리구가 가장 좋았다. 6. 접목융합의 정도에 따라 생육과 과실의 품질에 유의성이 있었다. 7. 종자의 크기가 클수록 발아율과 배축 굵기, 균일도 등이 높아 접목작업이 용이하여 접목능률을 향상시켰다. Effects of seeds size(small, medium and large) in watermelon(citrulus vulgaris schard) on seed germination, seedlings growth and the quality of fruit were investigated. The results are as followings. The seeds of watermelon were classified according to the weight of seeds into 3 groups, small (〈34mg), medium(44-35mg) and large( 〉45mg). Germination rate increased from 91.9% to 97% as the seed size increased. Hypocotyle thickness increased from 1.1mm to 1.5mm as the size of seeds increased. The heavier root weight was the larger the seeds were. The quality of seedlings improved as the seed size increased. Fruit quality was better at larger seed. At the same time, the efficiency of grafting improved since larger seeds produced higher uniformity at germination rate and hypocotyl thickness. The fruit weight was 6.6kg at 7-8 node, 7.4kg at 9-10kg and 7.2kg at 11-13kg.