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.

CMOS 연산 증폭기 및 비교기 회로의 자동 설계

신현우,김천호,김득경,신창호,신경욱 國立金烏工科大學校附設生産技術硏究所 1994 産業技術開發硏究 Vol.10 No.-

The paper describes a CMOS analog circuit design tool, K_ACD(Kumoh_Analog Circuits Designer), and design results. The K_ACD was developed for automatic design of fundamental analog circuit blocks such as comparator, unbuffered OP AMP, and buffered OP AMP. For given specifications and process parameters, it computes bias currents, transistor sizes, voltage gain, and power dissipation, then SPICE simulations are automatically carried out. Some design examples show usefulness of the K_ACD in analog circuit designs.

한국형 고속전철 집전 시스템의 동적설계에 관한 연구

허신(Hur Shin),경진호(Kyung Jin-Ho),송달호(Song Dahl-Ho) 한국철도학회 1998 한국철도학회 학술발표대회논문집 Vol.- No.-

The dynamic performance design of catenary-pantograph system which collects current for the next generation Korean high speed train(KHST) was considered. Used was the same dynamic model of the catenary-pantograph system as that of TGV-K which will be introduced for Kyung-bu corridor. Using the model, sensitivity analysis for design variables were made to improve dynamic performance of KHST system. The results of sensitivity analysis and performance improvement are as follows: (1) It was found that aerodynamic force, tension of contact wire, mass of contact strip, mass of supporting contact strip, mass of clamp, mass of steady arm, and stiffness of plunger were the design variables most influencing the dynamic performance of the system. (2) Pantograph with reductions of 20% aerodynamic force, 34% weight of supporting contact strip, 20% spring constant of plunger, and 34% equivalent mass of steady arm was very possible system for the KHST which will be running at maximum operating speed 350 ㎞/h.

대요근 근구 차단술의 해부학적 고찰 및 임상 효과

신경호,김헌,최락민,김희상,안경회 大韓再活醫學會 2000 Annals of Rehabilitation Medicine Vol.24 No.2

우수방사성의약품 생산시설 개발

신병철,정원명,박상현,이규일,박경배,박진호 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.2

Manufacturing facilities of the pharmaceuticals must meet certain level of the cleanness required so that foreign substances such as dust, moisture, heat, microorganism, or virus do not contaminate the product. In case of radiopharmaceuticals for medical treatment and diagnosis, not only should the operators and environment be protected from radiation but also need to be isolated from the foreign contaminant. Therefore, manufacturing facilities for radiopharmaceuticals must satisfy the design standards of both hot cell and clean room which are specified by GNP. However, standards of maintaining negative pressure for preventing spread of radioactive contaminant in isolated facilities conflict with the standards of maintaining positive pressure for keeping cleanness. To solve this problem, are pressure of hot cell was designed lower than in the adjacent area to meet standards of the radiation safety. To keep higher cleanness in certain part of the hot cell for filling, minimal relative positive pressure allows. In order to effectively maintain the cleanness that is required for production of Tc-99m generator, which takes 70% of whole demand of radiopharmaceuticals, the rooms placed in each side of production room are used as a buffer area and three lead hot cells are installed in production room. In this research, we established the appropriate engineered design concept for Tc-99m generator manufacturing facility, which satisfies both GMP cleanness standard for preventing particles, bacteria, other contaminants and the regulations of radiation safety for supervising and controlling the amount of radiation exposure and exhausted radioactivity. And the concept of multi-buffer zones is introduced to apply negative air pressure for hot cell with first priority and to continue relative positive air pressure for clean room.

전자선으로 전처리한 하수슬러지의 혐기성소화공정에 관한 연구

신경숙,강호 충남대학교 환경문제연구소 2000 環境硏究 Vol.18 No.-

To treat a large amount of sewage sludge generated from wastewater treatment plants, various pretreatment processs have been developed for the subsequent anaerobic digestion. As one of the processes, the pretreatment with electron beam irradiation has been investigeted. The SCFMRS were run to evaluate their reactor performance of sludge with and without irradiation by electron beam. The dewaterbility of digested sludge, which is derived from SCFMR, was also measured by Specific Resistance to Filtration(SRF) and Capillary Sunction Time(CST). The biogas productivity of SCFMR fed with 6kGy irradiated sludge showed 0.10∼0.14m3/m3-d at the HRT of 20days. It appeared 3∼5 times higher than that of unirradiated sludge in SCFMR. Consequently, TVS and COD removal efficiencies in the SCFMR fed with 1∼6kGy irradiated sludge were 30∼55% and 32∼52%, respectively, which were 20∼35% higher than those of unirradiated sludge as a function of irradiated dosages. The SRF of digested sludge pretreated with electron beam is 2.2 times lower than that of irradiated sludge. In conclusion, electron beam treatment on sewage sludge could accerlerate organic degradation rate and also enhance the dewaterbility of divested sludge.

원전의 가동중검사 관련 각국의 기술기준 비교고찰

신호상,김경조,장창희,강석철 한국비파괴검사학회 2004 한국비파괴검사학회지 Vol.24 No.2

각국의 법령에서는 원자력발전소에서 발생할 수 있는 사고로부터 국민의 건강과 재산을 보호하기 위해 원자력발전소의 압력경계 주요 용접부 등에 대해서는 주기적으로 열화의 정도를 파악하기 위한 가동중 비파괴검사를 수행하도록 규정하고 있으며, 이를 뒷받침하기 위한 가동중검사 기술기준을 제정하여 이행하고 있다. 최근 리스크를 반영한 가동중검사 프로그램을 개발하여 적용을 시도하고 있지만, 기존의 결정론적 검사대상 선정 프로그램은 아직도 상당한 의미가 있다고 할 수 있다. 본 논문에서는 가동중검사에 관한 선진국 즉, 미국, 프랑스, 캐나다, 일본 등의 기술기준과 IAEA에서 제시하는 안전지침에 비교검토를 통하여 현재 국내 가동중검사 기술기준의 개선방안을 모색하고자 하였다. In each country, the periodic ISI(In-Service Inspection) is required by the law to protect the public health and property from the potential accident of the nuclear facilities. To support the implementation of ISI program, the prescriptive ISI technical standards have been established. As the key parts of the ISI program, the non-destructive examination techniques are widely used to identify the degree of degradation of the pressure boundary components and welds. Recently, the risk informed-ISI program has been developed and implemented in several countries. Nonetheless, the existing ISI program which prescriptively decides the scope of inspection still has its own significance. In this article, the technical standards of ISI in leading countries like US, France, Canada, and Japan are reviewed and compared with the safety guide by IAEA. An outline to revise the domestic technical standards of ISI has been suggested.

머리부분에 방사선조사를 받은 흰쥐 샘뇌하수체의 변화에 대한 면역전자현미경적 연구

신기호,박경호,안의태,양남길,고정식 순천향의학연구소 1995 Journal of Soonchunhyang Medical Science Vol.1 No.2

본 실험은 과다한 X-선에 머리부분이 노출되었을 때, 샘뇌하수체의 변화를 알아보기 위하여 시행하였다. 체중 200-250g의 Sprague Dawley계 숫흰쥐를 실험동물로 사용하였으며, 정상군과 방사선조사군으로 나누었다, 방사선조사군은 조사량에 따라 3,000 rad 조사군과 6,000 rad조사군으로 나누어, 방사선 조사후 6시간, 2일 및 6일 후에 도살하여 조직을 절취하였다. 방사선조사는 흰쥐를 sodium thiopental로 마취한 후 방사선선형가속기(Mitsubishi Linear Accelerator ML-4MV)를 사용하여 머리부위를 조사하였다. 조사조건은 조사거리 80 cm, 조사구역 30 cm X 30 cm, 조사깊이 1.2 cm(100% skin dose)였으며, 분당 200 rad씩 조사하였다. 샘뇌하수체는 1% glutaraldehyde- 1% paraformaldehyde액으로 일차 고정한후, 2% osmium tetroxide액에 이차고정하였으며, 고정이 끝난 조직은 alcohol과 acetone으로 탈수한 후 araldite혼합액에 포매하였다. 포매된 조직은 , LKB-V ultratome으로 60-70nm두께의 절편을 작성하여 300 mesh nickel grid에 붙인 다음 젖샘자극호르몬과 성장자극호르몬에 대한 단독면역염색 및 이중면역염색을 시행하였다. 면역염색이 끝난 절편은 uranyl acetate와 lead citrate로 염색한후, JEM 100CX-Ⅱ 전자현미경으로 관찰하여 다음과 같은 결과를 얻었다. 1. 젖샘자극호르몬분비세포는 불규칙한 모양을 한 큰 분비과립(300-700 nm)을 가진 성숙세포, 크기가 다양한 둥근 분비과립(150-200 nm)을 가진 중간 세포와 크기가 작은 둥근 분비과립(100-150 nm)을 가진 미성숙세포로 나눌 수 있었다. 2. 성장자극호르몬분비세포는 크고 둥근 분비과립(200-500 nm)을 가진 제 1 형 세포와 상대적으로 작고 둥근 분비과립 (150-200 nm)을 가진 제 Ⅱ형 세포로 나눌 수 있었다. 3. 방사선 조사후 6 시간군에서 3,000 rad에서는 큰 변화가 없었고, 6,000 rad에서는 사립체와 과립형질내세망의 수조 확장이 관찰되었다. 방사선 조사후 2일군에서는 큰 변화가 없었으며, 6일군에서는 핵막구조의 확장이 관찰되었다. 4. 세포의 종류도 젖샘자극호르몬분비세포는 3,000 rad 조사군과 6,000 rad 조사군 모두 2일군에서는 성숙형이 감소하고 중간형과 미성숙형이 자주 관찰되었으며, 6일군에서는 정상군과 같은 분포양상을 보였으나 분비과립의 금입자표지가 감소한 것을 관찰할 수 있었다. 성장자극호르몬분비세포에서는 뚜렷한 세포형이 분포변화는 관찰할 수 없었으나 금입자표지의 감소는 나타났다. 5. 방사선조사후 6시간군에서 부터 mammosomatography가 나타났는데, 한 세포 내에 젖샘자극호르몬과 성장자극호르몬을 지닌 분비과립이 함께 존재하였으며, 세포의 모양은 다핵세포의 형태를 하고 있는 것과 불규칙한 모양을 한 것이 있었는데, 이와같은 결과는 방사선조사 후 샘뇌하수체의 기능저하에 따른 보상작용으로 나타난 현상이라 생각된다. 이상의 결과로 보아 방사선 조사를 받은 초기에는 분비과립의 방출이 과다하게 일어나며, 방사선 조사의 영향으로 세포질소기관의 기능이 약화되어 6일이 지나면 샘뇌하수체의 호르몬분비능력이 저하되는 것 같다. This experiment was performed to study the morphological changes of the adenohypophysis of rat following X-ray irradiation. Male rats were divided into normal and X-ray irradiation groups. The heads of rat were exposed to 3,000 rads or 6,000 rads of radiation in a single dose. X-ray source was a Mitsubishi Linear Accelerator ML-4MV. Only the heads of animals were exposed at the distance of 80 cm, within the area of 30 X 30 cm, in the depth of 1 cm, with the speed of 200 rad/min. Animals of X-ray irradiation group were sacrificed on 6 hours, 2 days and 6 days after the irradiation. Tissue blocks of adenohypophysis were fixed in the 1% glutaraldehyde - 1% paraformaldehyde solution, followed by refixation in the 2% osmium tetroxide solution. Dehydradted blocks were embedded in araldite mixture. The sections were cut on a LKB V ultrotome, and ultrathin sections were places on bare nickel grid(200 mesh). The section-bearing grids were floated upside down on the solutions in a moisture chamber at room temperature. Sections were single immunostained or double immunostained for prolactin and/or growth hormone. And the sections were jet washed with distilled water. The immunostained sections were contrasted with uranyl acetate and lead citrate, and observed with JEM 100CX II electron microscope. The results were as follows: 1. Three types of the prolactin cells according to their size and shape of secretory granules were found; mature type cells contained large pleomorphic secretory granules(above 500 nm). intermediate type cells contained round granules of varying size(200-250 nm), and immature type cells contained small round granules(100 nm). 2. Two types of the growth hormone cells according to their size of secretory granules were found: type I cells contained large round secretory granules(200-300 nm) and type II cells contained small granules(100-200 nm). 3. Six hours after the irradiation, adenohypophysis showed swollen cisternae of granular endoplasmic reticulum and alterations of mitochondrial cristae, but only in doses of 6.000 rads. 4. Adenohypopysis showed decrease in number of mature type prolactin cells on 2 days after irradiatin, and recovered number of mature typer prolactin cell. but their immunoreactiveity were gradually decreased following the irradiation, as compared with that in normal adenohypophysis. 5. Six hours after the irradiation, mammosomatotrophs were found to contain prolactin and growth hormone within different granules each other. Some cells were multinucleated, and some cells exhibited irregular cytoplasmic processes. Summarizing the above results, adenohypophysis rapidly released the secretory granules after the irradiation, and cell organelles of prolactin cells and growth hormone cells were altered or degenerated. It means that adenohypophysis decreased its hormone producing activity on 6 days after irradiation.

만성신부전 환자에서 Recombinant Human Erythropoietin(rhEPO)의 피하주사시 생체이용율

김경수,이경훈,이영수,김광호,김용식,신상구,박찬웅 大韓臨床藥理學會 1993 臨床藥理學會誌 Vol.1 No.1

교육투자가 임금에 미치는 효과에 관한 실증분석

신경수,송일호 東國大學校 社會科學硏究院 2005 사회과학연구 Vol.12 No.1

The purpose of this study is to estimate the effect of educational investment on wage. According to the empirical results, the wage gaps for each education level are observed significantly, because the higher education level means to get more earnings. Moreover, the wage premium of middle school is almost vanished. This study also explores the marginal rate of returns of educational investment. First of all, the marginal rates of returns in high school and university have drastically declined since 2000. The marginal rates of returns in college graduates has drastically increased since 2000. Secondly, the marginal rate of returns of female is superior to that of male. Third, as the marginal rate of returns to education in middle school is decreased rapidly, that is almost vanished at present. In addition, this study estimates the marginal rate of returns to education by education level. The marginal rate of returns of university graduates is the highest, and that of high school graduates is better than that of college graduates. It also shows that the marginal rates of returns of college graduates exceeds that of university graduates. Finally, this study shows that the academic wage gap, that was declining after 1980's, has been increased since mid of 1990's. Second, the academic wage gap of female is higher than that of male.