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.

Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

Validation of the oxford classification of iga nephropathy: A Single-Center Study in Korean Adults

( Ho Young Lee ),( Sul Hee Yi ),( Mi Seon Seo ),( Jin Nam Hyun ),( Jin Seok Jeon ),( Hyunjin Noh ),( Dong Cheol Han ),( Seung Duk Hwang ),( So Young Jin ),( Soon Hyo Kwon ) 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.3

Background/Aims: The recently published Oxford classification of IgA nephropathy (IgAN) proposed a split system for histological grading, based on prognostic pathological features. This new classification system must be validated in a variety of cohorts. We investigated whether these pathological features were applicable to an adult Korean population. Methods: In total, 69 adult Korean patients with IgAN were analyzed using the Oxford classification system at Soonchunhyang University Hospital, Seoul, Korea. All cases were categorized according to Lee`s classification. Renal biopsies from all patients were scored by a pathologist who was blinded to the clinical data for pathological variables. Inclusion criteria were age greater than 18 years and at least 36 months of follow-up. We excluded cases with secondary IgAN, diabetic nephropathy combined other glomerulopathies, less than 36 months of follow-up, and those that progressed rapidly. Results: The median age of the patients was 34 years (range, 27 to 45). Mean arterial blood pressure was 97 ± 10 mmHg at the time of biopsy. The median follow-up period was 85 months (range, 60 to 114). Kaplan-Meier analysis showed significant prognostic predictions for M, E, and T lesions. A Cox proportional hazard regression analysis also revealed prognostic predictions for E and T lesions. Conclusions: Using the Oxford classification in IgAN, E, and T lesions predicted renal outcome in Korean adults after taking clinical variables into account.

조구등(釣鉤藤)의 4-VO로 유발한 흰쥐뇌허혈에 대한 신경방어효과

李仁煥,林康鉉,李鍾錫,石庚浩,安德均,朴虎君,김頀哲 대한본초학회 1999 大韓本草學會誌 Vol.14 No.2

Uncariae Ramulus et Uncus(UR, ???) has sweet in flavour and slightly cold in property, acting on the liver and pericardium channels. This drug was described in a medical classic as having the ability to remove "heat", check hyperfunction of the liver and relieve dizziness, tremors, and convulsion, and subdue "endogenous wind". So this study was planned to check the neuroprotective effect of UR on the global ischemia induced by 4-vessel occlusion in Wistar rats. and UR extract was lyophilized after extraction with 70% methanol. We induced 4-vessel occlusion for 10 minutes and reperfused again. The number of CA1 pyramidal neurons were counted after 7 days of reperfusion under the cresyl violet staining. In 4-VO ischemia model, UR showed significantly neuroprotective effects(1,000 and 500 ㎎/㎏ of UR extracts, p<0.05) compared with control group. Each neuroprotective ratio was about 23.0%, 19.0% respectively. Consequently, Uncariae Ramulus et Uncus has neuroprotective effects on the global ischermia induced by 4-vessel occlusion in Wistar rats. So we expect that Uncariae Ramulus et Uncus can be used as a drug for neurodegenerative disease.

크론병에 대한 CoPPLX의 방어효과에 대한 연구

이호학,김유림,문창기,이재일,양병윤,김종수,이정민,정재혁,안석진,박상준,김윤권,김소연,김영중,조민구,최영자,장성조 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

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.

Ln₃Ba?Co₄O? (Ln = Sm, Pr, Er, Gd, Ho) 상의 합성과 결정구조에 관한 연구

송민석,이재열,송수호 嶺南大學校 工業技術硏究所 1998 工業技術硏究所論文集 Vol.26 No.2

The Ln₃Ba?Co₄O? phases were synthesized with Pr?O? Sm₂O₃, Er₂O₃, Gd₂O₃, Ho₂O₃, BaCO₃, and Co₃O₄by solid state reaction at 1200℃ with intermittent grinding. The phases with Pr and Sm formed hexagonal structure isostructural with Nd₃Ba?Co ₄O? phase Whereas the phases with Er, Ho, and Gd formed unknown cubic phases. The crystal structure of Sm₃Ba?Co₄O? phase were refined by X-ray diffraction powder data by means of Rietveld method. The starting model was based on the Nd₃Ba?Co₄O? structure. The Crystal system was hexagonal, space group P6₃mc, a=11.634(6)A, c=6.861(4)A for pr₃Ba?Co₄O? ; a=11.556(6)A, c=6.788(3)A for Sm₃Ba?Co₄O?. Final R values are : Rwp=0.121, Rp=0.084 for pr₃Ba?Co₄O?, Rwp=0.101, Rp=0.077 for Sm₃Ba?Co₄O? .

크롬(Ⅵ)의 체내 흡수와 소실속도에 관한 연구

김현영,이성배,임철홍,이권섭,정용현,이종성,한정희,전윤석,황호순,이용묵 한국산업위생학회 2003 한국산업보건학회지 Vol.13 No.1

The CrO3 mostly used in plating. metal surface disposal, leather, cosmetic manufacturing, as an experiment material by repeatedly inhaling and exposure the male S.D. rats at a 0.00, 0.2., 0.50, 1.25 mg/㎡ concentration(particle size: 0.5-0.5 aerosol)6hours a day, 5day a week in 13weeks comparing with 2weeks, 8weeks of recovery group about the noxiousness of the experiment animal and the reduce scale of the CrO3 in the internal organ especially in blook and respiratory organ with the period of convalescent and clearance. The experiment results which we received are as follows. 1. In blood the RBC, HGB and HCT experiment, rats with 0.20, 0.50 mg/㎡ concentration showed that there were some decreases but not dependent. The kidneys absolute weight compared with control group was reduced intentionally(p〈0.05) and the lungs absolute weight compared with control group showed intentional increase(p〉0.05). 2. After the exposure of the experiment material, the whole blook, l\blood plasma and red blood cell in blood by (x): the period of convalescent, per (y); the decreasing of Cr concentration, was y=66.51 e -0.057x, y=67.2 e-0.101x, y=70.01 e-0.030 in 0.50 mg/㎡ exposure concentration by calculating the clearance coefficient of correlation, and the half life (day)was estimated 12.0, 6086, 23.0 each. 3, After the exposure of the experiment material, the experiment animals lung, liver and kidneys by(x); the period of convalescent, per (y); the decreasing of Cr conentration, was y=1808 e-0.00493x, y=12.02e-0.0297x, y=67.61 e-0.0292x in 0.50mg/㎡ exposure concentration by calculating the clearance coefficient of correlation, and the half life(day)was estimated 140.6, 23.3, 23.7, each, and including lung, liver with all of the experiment internal organs, the Cr clearance decreased as the exposure concentration increased.