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.

三天地의 環境과 生物多樣性 : I. Enviornmental Factors and Flora I. 環境要因과 植物相에 關하여

신상천,이종운,배규호,전재인,강경화 嶺南大學校 基礎科學硏究所 1992 基礎科學硏究 Vol.12 No.-

Environmental factors and phytological aspects of Samchunimpoundment in Kyongsan, Kyongpook were studied. 40 quadrats in 4 sites had 94% herbaceous cover, 31% shrub cover and 18% tree cover. Ambrosia artemisiifolia var. elatior, Metaplexis japonica, Erigeron annuus, Humulus Japonicus, Eragrostis ferruginea, Artemisia princeps var. orientalis were dominant herbaceous species and found cultivated plants of Hordeumn vulgare var. hexastichon, Prunus persica, Morus alba and neophytes of Ambrosia artemisiifolia var. elatior, Erigeron canadensis, Erigeron annuus, Ailanthus altissima, Bidens bipinnata, Lactuca indica var. laciniata, Robinia pseudo-acacia, oenothera odorata, Euphobia maculata. The investigated sites were divided into 4 patterns based on the vegetation with high difference level and Ambrosia artemisiifolia var. elatior, Medicago sativa, Setaria viridis, Metaplexis japonica, Humulus japonicus, Calystegia japonica, Forsythia koreana, Lsctuca indica var. laciniata were different species group. More than 90% on the surface area of water mass covered with Nelumbo nucifera, Marsilea quadrifolia and Typha angustata and distributed Hydrilla verticillata, Ceratophyllum demersum, Trypa pseudo-incisa, Myriophyllum spicatum under water. Average data of environmental factor analysis are as followings; air temperature 25.8℃, ph 6.77, total hardness 117.94㎎/ℓ, SS 4.5㎎/ℓ,Do 3.3㎎/ℓ,BOD 6.6㎎/ℓ,COD 7.2㎎/ℓ,cl- 17.56㎎/ℓ,?? 7.14㎎/ℓ,Mn 0.05㎎/ℓ, Zn 0.04㎎/ℓ. Total quality of impoundment water were heavily polluted and were quality class Ⅳ.

鷄龍山 森林土壤의 特性에 關하여

辛昌男,宋鎬京,朴鍾聲 忠南大學校 環境問題硏究所 1983 環境硏究 Vol.1 No.2

In order to determine the characteristics of soil in Mt. Gyeryong, the content of primary minerals and chemical and physical properties of forest soil were analyzed. The parent rock of forest soil were consisted of pink feldspar granite and gneissose granite. The weathered parent rock contained about 64% of plagioclase and quartz. The content of available phosphorus of soil resulted from weathering process of pink feldspar granite was higher than that of the gneissose granite soil. But the contents of K and of the latter were higher than those of the former. Both types of soil texture were mainly loam and clay loam The differences of chemical soil properties between Pinetum consociation and Quercetum consociation were as follows:the contents of the organic matter, total exchangeable bases, NO^-_3-N and NH^+_4-N of Quercetum consociation were higher than as compared to those Pinetum consociation in the pink feldspar granite region, the contents of total nitrogen, available phosphorus, total exchangeable bases, Mg^++ and NO^-_3-N of Quercetum consociation were higher than as compared to those of Pinetum consociation in the gneissose granite region.

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.

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

18S-srRNA 분석에 의한 Acantbamoeba 한국 분리주들의 분류 검토

신호준,지영진,조명수,김형일,박연희,임경일 아주대학교 의과학연구소 1998 아주의학 Vol.3 No.2

Acanthamoeba spp. spread in soil, ponds, air and swimming pool, cause a granulomatous amoebic meningitis and amoebic keratitis in human and experimental animals. Their classification had depended upon morphological characteristics and physiological conditions such as thermophilic status and generation times. However, because amoeba species showed the morphological and physiological diversity in isolates, many attempts have been made on identification of Acanthamoeba spp. Restriction fragments length polymorphism (RFLP) analysis of IBS-small subunit ribosomal RNA (srRNA) was an useful tool for classification among morphologically and genetically closely-related species. In this study, 18S-srDNAs of amoebae were amplified by PCR with primer encoding 18S-srRNA gene and digested with restriction endonudeases, and RFLP analysis was applied on classification of Acanthamoeba Korean isolates (YM-4, YM-5 and YM-7), comparing with reference amoebae, A. culbertsoni, A. polyphaga and A. royreba. Trophozoites of six Acanthamoeba spp. had typical acanthopoda, but did not show any morphological differences. Cyst of Acanthamoeba sp. YM-7 was similar to that of A. polyphaga which was designated as group Ⅱ Acanthamoeba. Morphologically other amoebae belonged to group Ⅲ Acanthamoeba. Digestion of 18S-srDNA with six enzymes, Dde Ⅰ, Hae Ⅲ, Hind Ⅲ, EcoR Ⅰ, Rsa Ⅰ and Sph Ⅰ, resulted in various DNA fragments. Using the method of Nei and U (1979) for RFLP analysis, genetic divergence was not observed between A culbertsoni and Acanthamoeba sp. YM-4. Between A. culbertsoni and Acanthamoeba sp. YM-5, genetic distance was 0.070, 0.364 between Acanthamoeba sp. YM-4 and A. polyphaga, and 0.277 between Acanthamoeba sp. YM-7 and A. polyphaga. In comparison with A. culbertsoni and A. polyphaga, Acanthamoeba sp. YM-7 showed genetic distance of 0.330 and 0.154, respectively. Thus, Acanthamoeba sp. YM-7 is a similar species to A. polyphaga. Acanthamoeba sp. YM-5 is a different species from A. polyphaga, but closely-related to A. culbertsoni. Acanthamoeba sp. YM-4 can be classified as a subspecies or a strain of A. culbertsoni.

피임제(Norinyl)가 흰쥐 난소의 Alkaline Phosphatase 활성에 미치는 영향

신경숙,이군자,정호삼,이규식 대한해부학회 1985 Anatomy & Cell Biology Vol.18 No.1

In mammals, female sexual hormones secrete at different rate during the sexual cycle so that the follicular cells and the granulosa cells undergo structural and functional changes. Therefore the authors undertook to pursue the changes of the graafian follicle during the estrous cycle and the effect of the oral-contraceptive. Female Sprague-Dawley rats weighing 150g were used as a experimental animal. Vaginal smears were obtained daily and only animals that showed consecutive four-day estrous cycle were used. The animals of the oral-contraceptive administered groups were administered norinyl, dissolved in distilled-water. The ovary was fixed with 10% neutral formalin and sliced at 14 ㎛ thickness in a frozen cryostat. The activity of alkaline phosphatase was observed by the Gomori's method for histochemical study. The other ovary was homogenized and the homogenate was assayed by the Lowry's method for biochemical study. The results were as follows. 1) In the follicle alkaline phosphatase activity was positive in the theca layer while the granulosa layer was negative. Strong activity were shown at proestrous and metestrous stage during the estrous cycle. And alkaline phosphatase activity of the ovary did not change markedly during the estrous cycle but the activity of estrous stage were slightly higher than other stages. 2) In the norinyl-administered group, the alkaline phosphatase activity of the ovary did not change during the estrous cycle. And the activity of the administered groups was lower than the control group.