• 제목/요약/키워드: Nuclear localization

검색결과 308건 처리시간 0.027초

경수로핵연료 열수력 연구개발 분석 및 연산학 협력 성과 (Thermal-Hydraulic Research Review and Cooperation Outcome for Light Water Reactor Fuel)

  • 인왕기;신창환;이치영;이찬;전태현;오동석
    • 대한기계학회논문집B
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    • 제40권12호
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    • pp.815-824
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    • 2016
  • 가압경수로에 장전되는 핵연료집합체는 연료 봉 다발과 지지격자 및 상하단 고정체로 구성되어 있다. 고온 고압의 냉각수는 원자로 하부로 유입되어 연료 봉 사이로 형성된 부수로를 따라 노심 상부로 흐른다. 경수로핵연료의 주요 열수력 성능인자는 정상운전시 압력강하 및 임계열속이며 사고시에는 급랭 시간이다. 한국원자력연구원에서는 경수로핵연료의 성능을 향상시키고 국산화를 위해 고성능 경수로핵연료, 이중냉각 핵연료 및 사고저항성 핵연료를 개발하였다. 경수로핵연료의 열수력 핵심기술을 개발하기 위해 압력강하 실험, 난류 유동혼합/열전달 실험, 임계열속 및 급랭 시험을 수행하였으며 전산유체역학 방법도 활용하였다. 더불어 사용후핵연료의 임시저장을 위한 건식저장 용기의 열유동에 대한 전산유체해석을 수행하였다. 한편, 경수로핵연료의 열수력 기반기술을 개발하고 실용화를 위해 대학 및 산업체와 협력연구도 진행하였다.

대장암 세포주 SNU C2A에서 etoposide 처리에 의한 apoptosis 유도 (Induction of apoptosis by etoposide treatment in colon cancer cell line SNU C2A)

  • 정지연;나윤숙;정호철;오상진
    • IMMUNE NETWORK
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    • 제1권3호
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    • pp.221-229
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    • 2001
  • Background: Inactivation of tumor suppressor genes is believed to be important in the development of many human malignancies. Recently, several lines of evidence have indicated that the wild type p53 gene located at 17p13.3, may function as a tumor suppressor gene and that a mutant p53 gene could promote transformation by inactivating normal p53 function in a dominant negative fashion. These broad spectrum of p53 mutation in human cancers provide that mutant p53 and their protein may be potential targets of tumor diagnostic and therapeutic interventions. Method: Colony formation was performed to investigate growth suppressional ability. p53 expression pattern was examined by western blot and p53-mediated transactivation ability was assessed by CAT activity. SNU C2A cells were observed in apoptotic aspects induced by etoposide and $H_2O_2$ treatment, detecting sensitivity on agent, DNA fragmentation through agarose gel, chromatin condensation by fluorescence microscope, and cell cycle distribution by FACS. Result: 1) p53 mutant his179arg ($histidine{\rightarrow}arginine$) detected in SNU C2A cells lost transcriptional activity and growth suppression ability, showing dominant negative effect on its wild type p53. 2) Etoposide-treated SNU C2A cells induced apoptosis, exhibiting dramatic reduction of cell growth, DNA fragmentation, nuclear condensation formation of apoptotic body and increment of sub-G1 cell fraction. 3) Etoposide and $H_2O_2$-treated SNU C2A cells have no high increase of p53 expression and overexpressed p53 protein changed localization, from cytoplasm to nucleus. Also, p53-mediated transcriptional activity was increased by agents-treatment. Conclusion: SNU C2A cells coexpress wild-type and mutant p53 protein induced apoptosis in the condition on DNA damage, through localizational shift from cytoplasm to nucleus of p53 protein rather than the induction of p53 protein. SNU C2A cells derived mutant p53 his179arg abrogated both the growth supression ability and transactivational activity, showing inhibition effect on transcriptional activity of wild type p53, but did not repress the activity of wild type p53 in SNU C2A cells owing to dominant activity of wild type. These cell condition may provide new gene therapeutic implications leading effective antiproliferation of cell when mutant and wild-type p53 protein were co-expressed in cell.

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Garcinol, an Acetyltransferase Inhibitor, Suppresses Proliferation of Breast Cancer Cell Line MCF-7 Promoted by 17β-Estradiol

  • Ye, Xia;Yuan, Lei;Zhang, Li;Zhao, Jing;Zhang, Chun-Mei;Deng, Hua-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권12호
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    • pp.5001-5007
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    • 2014
  • The acetyltransferase inhibitor garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Anti-cancer activity has been suggested but there is no report on its action via inhibiting acetylation against cell proliferation, cell cycle progression, and apoptosis-inhibtion induced by estradiol ($E_2$) in human breast cancer MCF-7 cells. The main purposes of this study were to investigate the effects of the acetyltransferase inhibitor garcinol on cell proliferation, cell cycle progression and apoptosis inhibition in human breast cancer MCF-7 cells treated with estrogen, and to explore the significance of changes in acetylation levels in this process. We used a variety of techniques such as CCK-8 analysis of cell proliferation, FCM analysis of cell cycling and apoptosis, immunofluorescence analysis of NF-${\kappa}B$/p65 localization, and RT-PCR and Western blotting analysis of ac-H3, ac-H4, ac-p65, cyclin D1, Bcl-2 and Bcl-xl. We found that on treatment with garcinol in MCF-7 cells, $E_2$-induced proliferation was inhibited, cell cycle progression was arrested at G0/G1 phase, and the cell apoptosis rate was increased. Expression of ac-H3, ac-H4 and NF-${\kappa}B$/ac-p65 proteins in $E_2$-treated MCF-7 cells was increased, this being inhibited by garcinol but not ac-H4.The nuclear translocation of NF-${\kappa}B$/p65 in $E_2$-treated MCF-7 cells was also inhibited, along with cyclin D1, Bcl-2 and Bcl-xl in mRNA and protein expression levels. These results suggest that the effect of $E_2$ on promoting proliferation and inhibiting apoptosis is linked to hyperacetylation levels of histones and nonhistone NF-${\kappa}B$/p65 in MCF-7 cells. The acetyltransferase inhibitor garcinol plays an inhibitive role in MCF-7 cell proliferation promoted by $E_2$. Mechanisms are probably associated with decreasing ac-p65 protein expression level in the NF-${\kappa}B$ pathway, thus down-regulating the expression of cyclin D1, Bcl-2 and Bcl-xl.

Nanopharmaceutical Approach for Enhanced Anti-cancer Activity of Betulinic Acid in Lung-cancer Treatment via Activation of PARP: Interaction with DNA as a Target -Anti-cancer Potential of Nano-betulinic Acid in Lung Cancer-

  • Das, Jayeeta;Samadder, Asmita;Das, Sreemanti;Paul, Avijit;Khuda-Bukhsh, Anisur Rahman
    • 대한약침학회지
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    • 제19권1호
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    • pp.37-44
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    • 2016
  • Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

Increased Primary Cilia in Idiopathic Pulmonary Fibrosis

  • Lee, Junguee;Oh, Dong Hyun;Park, Ki Cheol;Choi, Ji Eun;Kwon, Jong Beom;Lee, Jongho;Park, Kuhn;Sul, Hae Joung
    • Molecules and Cells
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    • 제41권3호
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    • pp.224-233
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    • 2018
  • Primary cilia are solitary, non-motile, axonemal microtubule-based antenna-like organelles that project from the plasma membrane of most mammalian cells and are implicated in transducing hedgehog signals during development. It was recently proposed that aberrant SHH signaling may be implicated in the progression of idiopathic pulmonary fibrosis (IPF). However, the distribution and role of primary cilia in IPF remains unclear. Here, we clearly observed the primary cilia in alveolar epithelial cells, fibroblasts, and endothelial cells of human normal lung tissue. Then, we investigated the distribution of primary cilia in human IPF tissue samples using immunofluorescence. Tissues from six IPF cases showed an increase in the number of primary cilia in alveolar cells and fibroblasts. In addition, we observed an increase in ciliogenesis related genes such as IFT20 and IFT88 in IPF. Since major components of the SHH signaling pathway are known to be localized in primary cilia, we quantified the mRNA expression of the SHH signaling components using qRT-PCR in both IPF and control lung. mRNA levels of SHH, the coreceptor SMO, and the transcription factors GLI1 and GLI2 were upregulated in IPF compared with control. Furthermore, the nuclear localization of GLI1 was observed mainly in alveolar epithelia and fibroblasts. In addition, we showed that defective KIF3A-mediated ciliary loss in human type II alveolar epithelial cell lines leads to disruption of SHH signaling. These results indicate that a significant increase in the number of primary cilia in IPF contributes to the upregulation of SHH signals.

자기공명영상과 PET/CT를 중심으로 한 전립선 암의 영상 진단 (Imaging Assessment of Primary Prostate Cancer, Focused on Advanced MR Imaging and PET/CT)

  • 장진희;변재영;김민성;이영준;오순남;나성은;유이령
    • Investigative Magnetic Resonance Imaging
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    • 제12권2호
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    • pp.89-99
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    • 2008
  • 전립선 암은 종양 영상 분야에서 가장 어려운 분야 중 하나이다. 술전 영상 검사를 통한 전립선 암의 발견 (detection), 정위 (localization) 그리고 병기결정(staging)은 여전히 영상의학과 의사의 도전이 필요한 분야이다. 자기공명 영상은 우수한 연부 조직 대조를 보이며 여러 고형 장기의 영상에 널리 쓰이나, 전립선의 술전 자기공명 영상의 결과는 기대에 미치지 못한다. 전산화단층촬영 영상과 결합된 양전자방출단층촬영술 (PET/CT)은 종양 영상의 발달에 획기적인 기여를 하였으나, 전립선암의 평가에는 어려움이 많다. 최근에 이러한 불충분한 정확도를 극복하기 위하여 발전된 자기공명 영상 기법과 PET/CT을 이용한 전립선암 영상에 대한 연구들이 발표되었다. 본 종설에서는 새로운 기법의 자기 공명 영상과 PET/CT 영상을 중심으로 전립선암의 다양한 영상법과 그 소견을 살펴볼 것이다.

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비 생물학적 스트레스 시 벼에서 OsABF3 유전자 분리와 ABA 신호전달 대한 연구 (Studies on OsABF3 Gene Isolation and ABA Signal Transduction in Rice Plants Against Abiotic Stress)

  • 안철현;박훤범
    • 한국자원식물학회지
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    • 제30권5호
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    • pp.571-577
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    • 2017
  • ABA는 식물에서 비 생물학적 스트레스 내성에 관여하는 중요한 식물 호르몬이다. 애기장대의 group A bZIP 전사인자는 ABA 신호전달 과정에 중요한 역할을 한다고 알려져 있다. 그러나 벼에서는 group A bZIP 전사인자의 기능이 잘 알려져 있지 않다. 따라서 우리는 벼에서 group A bZIP 전사인자인 OsABF3(Oryza sativa ABA responsive element binding factor 3)를 연구하였다. 이를 위해 벼의 다양한 조직과 다양한 스트레스(가뭄, 염분, 저온, ABA, 산화 스트레스)에 따른OsABF3발현 패턴을 분석하였다. 또한 maize의 원형질체에서 GFP fusion 벡터를 사용한 세포 내 위치 분석을 통해 OsABF3가 핵단백질이라는 것을 확인하였다. Yeast one-hybrid 실험을 통해 OsABF3의 C-terminal 부분이 ABREs에 결합한다는 것과 N-terminal 부분이 하위 유전자의 transactivation 하는데 필요하다는 것을 알 수 있었다. 그리고 T-DNA가 삽입된 OsABF3의 homozygous 돌연변이체가 야생형과 과발현체에 비해 발아와 발아 후 단계에서 고농도의 ABA에 대한 민감도가 더 감소한 것을 알 수 있었다. 결과적으로 종합해 볼 때 OsABF3는 ABA의 의존적인 경로를 통해 비 생물학적 스트레스에 반응하는 유전자의 발현을 조절하는 기능을 하는 전사 조절자이다. 또한 OsABF3의 transactivation을 측정하는 실험에 있어서 억제 domain이 존재한다는 결과를 얻었다.

생쥐 망막에서 콜린성 무축삭세포의 분포 양상 및 연접회로에 대한 연구 (Morphology and Synaptic Connectivity of Cholinergic Amacrine Cells in the Mouse Retina)

  • 강화선;천명훈
    • Applied Microscopy
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    • 제34권4호
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    • pp.285-294
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    • 2004
  • 생쥐의 망막에서 아세틸콜린의 합성효소인 choline acetyltransferase (ChAT)에 대한 항체를 이용한 면역세포화학법으로 콜린성 무축삭세포를 동정하고 분포양상을 조사하였다. 콜린성 무축삭세포는 망막에서 세포체의 위치에 따라서 두 종류로 구분된다. 즉 속핵층에 세포체가 위치하고 세포돌기는 속얼기층의 a 아층판에 위치하는 세포와 세포체가 신경절세포층에 위치하면서 세포돌기는 b 아층판에 위치하는 세포이다. GABA 항체를 이용한 이중 면역염색 결과 모든 콜린성 무축삭세포가 GABA에 대한 염색반응성을 나타내었다. 전자현미경 관찰 결과 콜린성 무축삭세포의 연접회로가 속얼기층에서 관찰되었다. 콜린성 무축삭세포는 두극세포와 가장 많은 수입연접을 형성하고 있었으며, 이 외에 콜린성 무축삭세포와 염색되지 않은 무축삭세포와의 연접도 관찰되었다. 콜린성 무축삭세포의 수출연접의 주요 대상은 신경절세포로 속얼기층의 b 아층판에서 더 빈번하게 관찰되었다. 이러한 연구결과로 생쥐 망막의 콜린성 무축삭세포도 다른 종류의 포유류와 매우 유사한 특징을 가지고 있으며, 방향선택성 신경절세포로 신호가 전달되는 과정에서 중요한 역할을 할 것으로 생각된다.

Isolation and Molecular Characterization of a New CRT Binding Factor Gene from Capsella bursa-pastoris

  • Wang, Xinglong;Liu, Li;Liu, Sixiu;Sun, Xiaoqing;Deng, Zhongxiang;Pi, Yan;Sun, Xiaofen;Tang, Kexuan
    • BMB Reports
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    • 제37권5호
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    • pp.538-545
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    • 2004
  • A new CRT binding factor (CBF) gene designated Cbcbf25 was cloned from Capsella bursa-pastoris, a wild grass, by the rapid amplification of cDNA ends (RACE). The full-length cDNA of Cbcbf25 was 898 bp with a 669 bp open reading frame (ORF) encoding a putative DRE/CRT (LTRE)-binding protein of 223 amino acids. The predicted CbCBF25 protein contained a potential nuclear localization signal (NLS) in its N-terminal region followed by an AP2 DNA-binding motif and a possible acidic activation domain in the C-terminal region. Bioinformatic analysis revealed that Cbcbf25 has a high level of similarity with other CBF genes like cbf1, cbf2, and cbf3 from Arabidopsis thaliana, and Bncbf5, Bncbf7, Bncbf16, and Bncbf17 from Brassica napus. A cold acclimation assay showed that Cbcbf25 was expressed immediately after cold triggering, but this expression was transient, suggesting that it concerns cold acclimation. Our study implies that Cbcbf25 is an analogue of other CBF genes and may participate in cold-response, by for example, controlling the expression of cold-regulated genes or increasing the freezing tolerance of plants.

영양분이 결핍된 H460 세포주에서 자가포식이 세포사멸에 미치는 영향 (The Effect of Autophagy to Cell Death in Nutrient-Deprived H460 Cells)

  • 장혜연;조향정;황기은;김소영;이강규;문성록;신정현;조경화;이미경;이삼윤;박순아;박종군;김휘정;양세훈
    • Tuberculosis and Respiratory Diseases
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    • 제69권2호
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    • pp.81-94
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    • 2010
  • Background: Autophagy is an important adaptive mechanism in normal development and in response to changing environmental stimuli in cancer. Previous papers have reported that different types of cancer underwent autophagy to obtain amino acids as energy source of dying cells in nutrient-deprived conditions. However, whether or not autophagy in the process of lung cancer causes death or survival is controversial. Therefore in this study, we investigated whether nutrient deprivation induces autophagy in human H460 lung cancer cells. Methods: H460, lung cancer cells were incubated in RPMI 1640 medium, and the starved media, which are BME and RPMI media without serum, including 2-deoxyl-D-glucose according to time dependence. To evaluate the viability and find out the mechanism of cell death under nutrient-deprived conditions, the MTT assay and flow cytometry were done and analyzed the apoptotic and autophagic related proteins. It is also measured the development of acidic vascular organelles by acridine orange. Results: The nutrient-deprived cancer cell is relatively sensitive to cell death rather than normal nutrition. Massive cytoplasmic vacuolization was seen under nutrient-deprived conditions. Autophagic vacuoles were visible at approximately 12 h and as time ran out, vacuoles became larger and denser with the increasing number of vacuoles. In addition, the proportion of acridine orange stain-positive cells increased according to time dependence. Localization of GFP-LC3 in cytoplasm and expression of LC-3II and Beclin 1 were increased according to time dependence on nutrient-deprived cells. Conclusion: Nutrient deprivation induces cell death through autophagy in H460 lung cancer cells.