PGA2-induced expression of HO-1 is mediated by transcriptional upregulation of Nrf2

Sang-sun Lee,Yun-Jeong Choe,Hyein Lee,Sun-Young Lee,Ho-Shik Kim 대한독성 유전단백체 학회 2019 Molecular & cellular toxicology Vol.15 No.2

Backgrounds: Prostaglandin (PG) A2 reportedly stimulated expression of heme oxygenase (HO)-1 at the level of transcription via the activation of p38MAPK. Details of the mechanism, however, have not been provided, and this includes identification of the transcription factors responsible for PGA2-induced HO-1 expression. Herein is described an analysis of the role of nuclear factor erythroid 2 related factor 2 (Nrf2) and how PGA2 increases the activity of Nrf2 during PGA2-induced HO-1 expression. Methods: Expressions of HO-1 and Nrf2 were analyzed at the levels of both mRNA and protein. Nrf2 siRNA, SB203580, an inhibitor of p38MAPK, and scavengers of reactive oxygen species (ROS) were used to identify the effects of Nrf2, p38MAPK and ROS on PGA2-induced HO-1 expression. Results: Although SB203580 suppressed PGA2-induced HO-1 expression, genetic activation of p38MAPK could not stimulate the transcription of HO-1. Cycloheximide (CHX), an inhibitor of protein translation, almost completely prevented PGA2-induced increase of HO-1 transcription, but it did not prevent the phosphorylation of p38MAPK, which suggests that both de novo protein synthesis and p38MAPK activity are required to induce the transcription of HO-1 in response to PGA2 treatment. In addition, PGA2 increased the level of both Nrf2 mRNA and protein in a dose-dependent manner. Knockdown of Nrf2 using small interfering RNA (siRNA) suppressed PGA2-induced HO-1 expression. The PGA2-induced transcription of Nrf2 was prevented by ROS scavengers such as n-acetyl-l-cysteine and tempol but not CHX. Furthermore, siRNA against p38MAPK did not change the level of nuclear Nrf2 protein. Conclusion: These findings suggest that PGA2 induces HO-1 transcription via an increase in Nrf2 protein, the transcription of which is initiated by an accumulation of ROS that is independent of the p38MAPK activation pathway.

PGA2 induces the expression of HO-1 by activating p53 in HCT116 cells

Hyein Lee,Sang-Sun Lee,Ji-Young Park,Yun-Jeong Choe,이선영,Ho-Shik Kim,H.-S. Kim 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.2

Prostaglandin (PG) A2 which is a cytotoxic PG, was reported to induce the expression of heme oxygenase (HO)-1 via activation of p38MAPK to keep U2OS cells from cell cycle arrest in G2M phase. The expression of HO-1 is primarily regulated at the level of transcription. But the transcription factors that are responsible for PGA2-induced HO-1 expression were not clarified yet. Here, we report that PGA2-induced transcription of HO-1 is mediated by p53, a tumor suppressive transcription factor. In HCT116 cells, PGA2 treatment led to the phosphorylation of p53 and an increase of p21WAF1 transcription as well as the activation of HO-1 transcription. Knocking p53 down via RNA interference or inhibiting the p53’s transcriptional activity by pifithrin-α treatment led to suppression of the increase in the level of both HO-1 expression and activity of HO-1 promoter. Pretreatment of NU- 7441, a chemical inhibitor of DNA-activated protein kinase (DNA-PK), prevented both the PGA2-induced phosphorylation of p53 and an increase of HO-1 transcription. In addition, N-acetyl-l-cysteine, a scavenger of reactive oxygen species (ROS), also mimicked the effect of NU-7441 on the PGA2-induced activation of p53 and HO-1 transcription. Collectively, these results suggest that PGA2 induces the expression of HO-1 via activation of p53, which is mediated by the ROSDNA- PK pathway.

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes

Kim, Se-Jin,Ho Hur, Joon,Park, Channy,Kim, Hyung-Jin,Oh, Gi-Su,Lee, Joon No,Yoo, Su-Jin,Choe, Seong-Kyu,So, Hong-Seob,Lim, David J,Moon, Sung K,Park, Raekil Nature Publishing Group 2015 Experimental and molecular medicine Vol.47 No.2

<P>Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine <I>in vivo</I>. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.</P>

退溪의 人間學

崔升灝 東亞大學校 1972 東亞論叢 Vol.9 No.-

Toegye's pedagogical view was ethical and practical throughout. He urged that the aim of education should not be to train young men for the civil service examination alone. He insisted the importance of moral education as well. Knowledge, Virtue and Behavior are the three essential elements for perfectionof a man as such. In a word, Toegye maintained that education should aim at moulding young men into perfect men. Being an orthodox follower of Chuja, Toegye maintained the two elements of "Ri" and "Ki" as the cosmological principles. Ever since Chuja in 12th Century there were two schools as to which principle was the primary one, "Ri" or "Ki". The one was clualistic, maintaining that "Ri" and "Ki" were wholly different principles. The other monistic, maintaining "Ri" and "Ki" were one and the same principle. The prevalent view, however, was monistic one. This school maintained that the "Ki" was only a secndary principle and "Ri" was elemental or primary. Toegye belonged to this later school. Consequently, Toegye maintained that both the humannature and the Heaven's Law were merely twe different manifestation of one and the same principle of "Ri". As far as "Ri" concerned, both are the samo thing exactly. But the human nature, that is the pure "Ri", manifest itself always in Ki, and becomes human nature in reality. It is due to this fact that there are difference among men, bestowed each with clear or muddy, or pure or impure human nature. It is also due to whether the Ki, the container of Ri, is upright or oblique that there are wise men and folly man. However, the temper of men, which is the manifestation of Ki, is not, according to Toegye, unchangeablly fixed one like Ri. It has a potentiality for cultivation and refinement. Without this potentiality, education would be meaningless. Toegye's fundamental idea of education is to pursue "In" and virtue, and to cultivate piety and attain "Ri", the ultimate principle or truth. According to Toegye, "Ri" has tvo side, substance and operation. With regard the sub tance, Ri is eternally fixed. With regard to operation, it can be promoted and refined. Toegye emphasized the importance of the operational side of "Ri". In other words, he put stress oniideal operation of Ri, rather than the Being of Ri, that is description or onlotogical side of Ri. As a mean to achieve the ideal operation of Ri, Toegye insisted "Piety". According tohim, "Piety" is to play ther oleof a bridge between human nature and Heaven's law. "Piety" is the basis for intelligence and viruous behavior. It is only through realization of this Piety that one can attain the highest state of "In" Only through realization of Piety, one can rightly pursue Knowledge and virtue. Thus, "Piety" is the most fundamental concept in Toegye's anthropology.

극단 저체중 신생아에서의 동맥관 개존증 결찰술을 위한 진정맥 마취 경험 2례

최영균,고명진,이상은,조광래,김영환,임세훈,이정한,이근무,정순호,김영재,신치만 仁濟大學校 白病院 2010 仁濟醫學 Vol.31 No.-

Running title: Cases of anesthesia for extremely low birth weight infant. Extremely low birth weight infants (birth weight < 1000 g) are prone to various morbidities such as respiratory distress syndrome, intraventricular hemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotizing enterocolitis and retinopathy. To accomplish successful anesthetic management, many precautions must be continuously taken during the operation. First, inspired oxygen concentration should be adjusted to avoid oxygen toxicity. Second, body temperature must be maintained adequately. Third, hemodynamic parameters should be kept stable. We report 2 cases of successful anesthetic management for extremely low birth weight infant who underwent ligation of patent ductus arteriosus at the neonatal intensive care unit.

차세대 셀룰러 시스템을 위한 선형 예측전력제어 방식

최상호 가톨릭대학교 자연과학연구소 2003 자연과학논문집 Vol.24 No.-

차세대 셀룰러 CDMA 시스템에 적용하는 것을 목표로 한 새로운 선형예측 전력제어 방식을 제안하고, 예측필터를 기지국 내에 내장하여 역방향 링크의 복소 채널 신호를 직접 예측함으로써 기존 방식에 비해 mean square error를 줄이며 호환성 및 적응성면에서도 우위임을 보여준다. 예측전력제어에 사용되는 기존의 비적응 예측필터인 MMSE 필터보다 LS 필터나 RLS 필터가 mean square error를 줄일 수 있음을 보여준다. 특별히 시변 채널 하에서 적응성면 및 성능면을 고려할 때 RLS 필터가 가장 우위임을 보여준다. 예측전력제어 알고리듬에서는 단일 스텝 방식보다 다중 스텝 방식이 필터 추정에러를 줄여주어 전력제어 루프 성능을 개선함을 보여준다. This paper proposes a new linear predictive power control algorithm, being applicable to the next generation cellular CDMA systems, where the prediction filter that is built-into base station directly predicts the complex channel signal via the reverse link in order to reduce mean square error as well as to improve the system compatibility and adaptability. Compared to the existing non-adaptive predictive filter MMSE, LS filter or RLS filter reduce mean square error. Especially, in time-varying channels, RLS improves further over the other non-adaptive or adaptive schemes with respect to the adatability and the system performance. For the predictive power control algorithm the multi-step power control is superior to the single-step power control.

침습성 아스페르길수스증 진단을 위항 갈락토만난 항원검사의 유용성 평가

송경호,이신원,장희창,전재현,박완범,박경운,박상원,오명돈,최강원 대한감염학회 2009 감염과 화학요법 Vol.41 No.2

Background : Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. However, 1A is difficult to diagnose, especially in the aforementioned patient group. Recently, galactomannan assay (GMA) using enzyme immunoassay has been introduced in Korea. We evaluated its diagnostic usefulness in the diagnosis of 1A and we analyzed the results according to the underlying diseases. Materials and Methods : All patients who underwent GMA during the period from October 2007 to June 2008 were evaluated retrospectively. According to the criteria of European Organization for Research and Treatment of Cancer/Mycoses Study Group, IA was classified into four clinical categories: proven', probable', possible', and 'non' IA. Patients with 'proven' and 'probable' IA were used as the reference standards for IA. GMA was performed using Platelia Aspergillus EIA (Bio-Rad, Hercules, CA, USA). Optical density index ≥0.5 was considered positive. Results : Of the 144 patients who underwent GMA, two patients were classificed as proven' IA and sixteen patients were probable' 1A. Overall sensitivity, specificity, positive predictive value, and negative predictive value of the assay were 50% (95% confidence interval [C195), 26-74%), 88% (C195, 81-93%), 38% (CI95, 19-59%), and 93% (CI95, 86-97%), respectively. Among the 99 patients with underlying hematologic diseases, GMA showed 67% (C195, 35-90%) sensitivity and 89% (C195, 80-94%) specificity, whereas in 45 patients with underlying diseases other than hematologic diseases, sensitivity and specificity of the assay were 17% (CI95, 0-64%) and 87% (CI95, 73-96%), respectively. Conclusions : GMA showed high specificity, irrespective of the patient population. However, sensitivity of GMA was low and the assay was less sensitive in patients with underlying diseases other than hematologic diseases than in patients with hematologic diseases.

지역특화작목시험장의 혁신전파 유형화와 커뮤니케이션 만족도 연구

최상호,최영찬 한국농업교육학회 2008 농업교육과 인적자원개발 Vol.40 No.1

본 연구는 지역특화작목시험장에서 농업인에게 혁신기술을 전파하는 과정을 유형화하고,각 유형별로 나타나는 커뮤니케이션 특성과 만족도를 분석함으로써 지역 내 혁신전파역량 향상을 위한 시사점을 제시하는 것을 목적으로 한다. 이를 위해,지역특화작목시험장이 수행하고 있는 혁신전파활동방식과 농업인간의 상호작용수준을 중심으로 대응분석을 실시한 후,그 결과를 활용하여 군집분석을 실시하여 개별유형을 명명하였다. 최종적으로 분산분석을 실시하여 개별 유형별 성과 차이를 분석하였다. 이 과정 에서 280부의 농업인 설문자료가 최종적으로 활용되었다. 분석결과,혁신전파의 유형별 특성은 상호작용수준과 체계성만으로도 전체적인 설명과 유형화가 가능하였으며,개별 특성에 따른 유형은 ‘형식적지도형’,‘상황대응전파형’,‘농업인연계중시형’,‘체계적접근형’으로 구분되었다. 형식적지도형은 낮은 상호작용과 낮은 체계성을 통해 가장 기본적인 혁신전파활동을 유지하는 유형이며,상황대응전파형은 지역 내 실정과 작목특성,농업인과의 상호작용 방식 등이 복합적으로 작용하여,특정 형태의 상호작용수준이나 혁신전파활동으로 제한되지 않고 다변적으로 나타냐는 상황을 총괄하는 유형이다. 농업인연계중시형은 다소 낮은 체계성의 방식을 사용하나 농업인과의 높은 상호작용수준을 유지하면서 다양한 매체의 활용을 통해서 파트너쉽을 지속하는 형태이며,체계적접근형은 상호작용수준을 중시했다기 보다는 체계성이 유지하고 있는 상호작용의 발현으로 혁신전파활동을 유지하는 형태이다. 개별 유형별로 현장성,접근성,전달성,적용성에서 상황대응전파형,체계적접근형,형식적지도형,농업인연계중시형의 순으로 높게 나타났으며,개별 속성들간에는 유기적인 맥락이 존재하였다. This study differentiates innovation diffusion process of agricultural experiment station in terms of interaction and systematicity levels. The study use correspondence analysis to find relationship between interaction and system level. Then, extension and diffusion type of regional experimental station is classified based on the clustering analysis of 280 survey data obtained from farmers. The individual characteristics of 'formal extension type', 'situational reaction diffusion type', 'farmers connection type', and 'systematic approach type', all differentiated according to innovation diffusion patterns, were pre-defined. The formal extension type maintains the most basic innovation diffusion activities through low interaction and low systematicity. The situational reaction diffusion type oversees situations where the local situation, crop/plant characteristics, and methods of interaction with farmers act in a complex manner with considerable diversity., instead of being limited to specific forms of interaction levels or innovation diffusion activities, farmers connection type uses methods with relatively low system level but maintains a high level of interaction level with farmers, It also utilize partnership through the use of diverse media. The systematic approach type maintains innovation diffusion activities through interaction maintained by system level instead of focusing on interaction levels, In terms of individual types, immediacy, accessibility, referability, applicability, and satisfaction were the highest in the situational reaction diffusion type, systematic approach type, formal extension type, and farmers connection type, in the order. And there existed organic contexts among individual characteristics.

자궁경부암 냉동조직에서 Polymerase Chain Reaction (PCR)을 이용한 인 유듀종바이러스 (HPV)의 출현과 임상적 특징과의 연관성에 관한 연구

권선호,남상륜,이증훈,노재랑,최준호 충남대학교 의과대학 지역사회의학연구소 1995 충남의대잡지 Vol.22 No.1

Infection with human papillomavirus(HPV) is considered to be the principal causal agent in the development of the uterine cervical cancer. To detect HPV types prevalent in carcinoma of the uterine cervix, a type-specific, sensitive polymerase chain reaction(PCR)-based assay for HPV types 16, 18, and 33 was applied to 40 cervical carcinomas(39 squamous cell carcinomas and 1 adenocarcinoma), 6 cases of cervical intraepithelial neoplasia(CIN), and 18 samples of cervicitis and histologically normal cervix. PCR was done using 2 sets of Ll primer of HPV-16 and 18, 1 set of E2/E1 primer of HPV-33, and 3 sets of E6 primer of HPV-16, 18, 33. The amplified product was analyzed directly on the basis of the size of the ethidium bromide-stained band visible after agarose gel electrophoresis, which was confirmed by Southern blot hybridization. The results were as follows : 1. As expected, the combined incidence of the common high-risk genital HPVs(types 16, 18 and 33) was high in carcinomas (82.5%) and CIN 111(66.7%), low in CIN 1(33.3%), and nonexistent in the normal controls. 2. By using L1 primers and E1/E2 primers in 46 CINs and cervical carcinomas, HPV DNA was detected in 36(78.3%), which were 65.2%(30/46) for HPV 16, 8.7%(4/46) for HPV 33, 6.5%(3/46) for HPV-18, and only 1 case of mixed infection of HPV-16 and HPV-18 was detected. All normal cervices and cervicitis tissues were negative for HPV 16, 18 and 33. By using E6 primers, 35 (76.1%) cases were positive for HPV DNA, which were 67.4%(31/46) for HPV-16, 4.3%(2/46) each for HPV-18 and HPV-33. HPV 16 is the most common type present in squamous cell carcinoma. 3. There was no difference in detection rates of HPV DNA according to patients age in cervical carcinoma (p=0.188). 4. There were good correlation between the results obtained by PCR using Ll or E1/2 primer and those by E6 primer. The concordance rates were 93.8%(60/64) for HPV-16, 98.4% for HPV-18, and 96.9% for HPV-33. 5. There was no difference in detection rates of HPV DNA according to clinical stage in cervical carcinoma(p=0.2). 6. The detection rate of HPV DNA in case of serum SCC level under lOng/ml was 100%(17/17), which was higher than those in cases of serum SCC levels of 10ng/ml or more. "The detection rate was significantly decreased as serum SCC became high in level(p=0.012). 7. There was no difference in detection rates of HPV DNA according to tumor size in cervical carcinoma (p=0.743). 8. The reccurrence rate of patients with HPV-16 containing tumors was 28.6%((8/28), which was 3.4 times more than that of patients without HPV-16, but it was not statistically significant(p=0.162). The survival rate of patients with HPV-16 containing tumors was 82.1%, which was not different from from that of patients without HPV-16 containing tumrs(p=0.405). In conclusion, papillomavirus, especially HPV-16, played some role in the development of cervical cancer. There was no association between the HPV infection and the clinical characteristics including prognosis. However, in contrast to other studies, HPV type 18 and 33 were not the common type of HPV. Perhaps more cases should be analyzed.

전기경련요법에서 remifentanil이 혈역학에 미치는 효과

정순호,이상은,임세훈,이정한,이근무,최영균,김영재,신치만 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Objective: Electroconvulsive therapy (ECT) is often associated with transient hypertension and tachycardia. Acute hemodynamic change may produce serious complications. Remifentanil is a potent ultra short acting opioid and has been found to reduce blood pressure and heart rate. The goal of this study was to evaluate effects of remifentanil on seizure duration, recovery parameters and hemodynamic changes during ECT. Methods: Ten ASA Ⅰ, Ⅱ patients enrolled in this prospective, randomized trial, each receiving more than four electroconvulsive therapy. Patients were randomized to receive placebo, group P (propofol 1mg/kg+0.9% normal saline 1ml, n=10), and propofol with remifentanil, group R (propofol 1mg/kg+remifentanil 1ug/Kg n=10). Supplemental dose of propofol was given as required to achieve loss of consciousness. We recorded hemodynamic parameters, seizure duration, and recovery parameters. Results: Seizure duration and recovery parameters were similar in group R and group P. Blood pressure and Hear rate after ECT were significantly lower in group R. Conclusions: Remifentanil(1ug/kg) attenuated the acute hemodynamic response to ECT under propofol anesthesia without adversely affecting the duration of seizure activity and recovery profile. Adjunctive use of remifentanil may be good alternative regimens for ECT.