• Molecules and Cells
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• 제38권12호
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• pp.1029-1036
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• 2015

Appropriate vessel development and its coordinated function is essential for proper embryogenesis and homeostasis in the adult. Defects in vessels cause birth defects and are an important etiology of diseases such as cardiovascular disease, tumor and diabetes retinopathy. The accumulative data indicate that ETV2, an ETS transcription factor, performs a potent and indispensable function in mediating vessel development. This review discusses the recent progress of the study of ETV2 with special focus on its regulatory mechanisms and cell fate determining role in developing mouse embryos as well as somatic cells.

• Molecules and Cells
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• 제41권6호
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• pp.506-514
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• 2018

The transcriptional regulation of genes determines the fate of animal cell differentiation and subsequent organ development. With the recent progress in genome-wide technologies, the genomic landscapes of enhancers have been broadly explored in mammalian genomes, which led to the discovery of novel specific subsets of enhancers, termed super-enhancers. Super-enhancers are large clusters of enhancers covering the long region of regulatory DNA and are densely occupied by transcription factors, active histone marks, and co-activators. Accumulating evidence points to the critical role that super-enhancers play in cell type-specific development and differentiation, as well as in the development of various diseases. Here, I provide a comprehensive description of the optimal approach for identifying functional units of super-enhancers and their unique chromatin features in normal development and in diseases, including cancers. I also review the recent updated knowledge on novel approaches of targeting super-enhancers for the treatment of specific diseases, such as small-molecule inhibitors and potential gene therapy. This review will provide perspectives on using super-enhancers as biomarkers to develop novel disease diagnostic tools and establish new directions in clinical therapeutic strategies.

• BMB Reports
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• 제50권7호
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• pp.361-366
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• 2017

Tetraploidy, a potential precursor of cancer-associated aneuploidy, is produced either by cell fusion or failure of cytokinesis. In this study, low p53-expressing HeLa cells were used to address the fate of cancer cells after fusion. We found that massive cell death or growth arrest occurred a few days after fusion. Interestingly, cells with larger nuclei preferentially died after fusion, suggesting that a larger deviation of DNA content is a strong inducer of apoptosis. Notably, a fraction of cells escaped cell death. Also, the stability of survivin increased, and its localization changed preferentially to the cytosol in fused cells. Knockdown of survivin decreased the survival of fused cells, more than observed in unfused cells, showing increased dependency of fused cells on survivin. Collectively, after cancer cell fusion, some fused cells avoid the apoptotic crisis partly owing to survivin, and continue to proliferate, a process that contributes to human cancer progression.

• Genomics & Informatics
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• 제15권4호
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• pp.114-122
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• 2017

It is becoming increasingly clear that eukaryotic genomes are subjected to higher-order chromatin organization by the CCCTC-binding factor/cohesin complex. Their dynamic interactions in three dimensions within the nucleus regulate gene transcription by changing the chromatin architecture. Such spatial genomic organization is functionally important for the spatial disposition of chromosomes to control cell fate during development and differentiation. Thus, the dysregulation of proper long-range chromatin interactions may influence the development of tumorigenesis and cancer progression.

• 한국동물학회지
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• 제26권3호
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• pp.181-192
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• 1983

이차원 전긱영동법에 의하여 A. proteus의 tD strain과 tD strain이 박테리아와 공생에 의해 유도된 xD strain의 단백질 양성을 비교하였다. Silver stain에 의해 비교 가능한 200여개의 주요 단백질 가운데 tD strain에서 분자량 45,000, 동전점 5.9의 특이성 단백질이, xD strain의 세포액과 공생낭에서는 분자량 29,000, 동전점 5.5의 공생 특이성 단백질이 탐지되었다. 공생 특이성 단백질은 아메바 고은 배양 및 실험 공생 아메바를 이용한 실험 결과 박테리아와 직접 연관 되어 있었다. 탐지된 두 특이성 단백질에 대하여 종전의 세포 핵 이식 및 배양 실험을 통해서 얻어진 결과에 비추어 이들 단백질 상호 연관 및 세포내의 기능에 관하여 논의하였다.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.149-149
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• 2003

To understand environmental paths of the transport and accumulation of endocrine disrupting chemicals (EDCs), a single cell multimedia fate model has been constructed and evaluated. The EDCs of concern were PAHs, Organochlorine Pesticides (OCPs), PCBs, Alkyl phenols, and phthalates. An evaluation model was designed for the multimedia distribution, including air, water, soil, sediment and vegetation. This model was verified using reported values and via monitoring data. Based on collected data, the distribution trends of EDCs with respect to environmental media were analyzed. Those results have applied to the model for the prediction of the spatial and temporal distribution of EDCs in Seoul. Especially, phenol compound, phthalates, PAHs, PCBs and organochlorine pesticides were estimated and the model was verified. This model was successfully conducted to environmental media, such as air (vapor and suspended particles), soils (forest soil, bare soil, and cement-concrete covered soil), water (dissolved and suspended solids), sediment, trees (deciduous and coniferous). The discrepancies between the model prediction and the measured data are approximately within or near a factor of 10 for the PAHs of three rings through that of six rings, implying that multimedia distribution of the PAHs could be predicted with a factor of 10. Concerning about the air equilibrium may be assumed, a fugacity at steady state is similar in all environmental media. Considering the uncertainties of this model, the use of equilibrium models may be sufficient for assessing chemical fates. In this study, a suggestion was made that modeling and estimation of chemicals in environmental multimedia be rigorously evaluated using the measured flux data. In addition, these data should be obtained, for example, from the precise and standardized inventory of the target chemicals. The model (EDC Seoul) will be refined in an on-going research effort and will be used to support decision-making concerning the management of EDCs.

• International Journal of Oral Biology
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• 제37권2호
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• pp.63-68
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• 2012

It has been documented that SPA0355 exerts antiinflammatory effects via the inhibition of nuclear factor-kappaB activation. In present study, we investigated the inhibitory effects of SPA0355 on periodontitis in an animal model. Periodontitis was induced by ligation of the cervix of the 1st molar in the left mandible in rats. After ligature, the rats were randomly divided into four groups and topically applied with SPA0355 (0.5, 1, and 2%) or the vehicle alone once daily for 10 days. Body weight and food intake were measured daily throughout the experimental period. At day 10 post-ligature, the infiltration of inflammatory cells and distance of the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) in the distal area of ligatured tooth were estimated histopathologically. No changes in body weight or food intake were found between the control and SPA0355 groups. The degree of inflammation was decreased in all three SPA0355 application groups. A decrease CEJ-ABC distance was observed in the 0.5% and 1% SPA0355 groups. These results indicate that SPA0355 inhibits the infiltration of inflammatory cells and alveolar bone resorption and suggests its potential as a therapeutic agent for periodontitis.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.441-451
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• 2017

Imperatorin, a major bioactive furanocoumarin with multifunctions, can be used for treating neurodegenerative diseases. In this study, we investigated the characteristics of imperatorin transport in the brain. Experiments of the present study were designed to study imperatorin transport across the blood-brain barrier both in vivo and in vitro. In vivo study was performed in rats using single intravenous injection and in situ carotid artery perfusion technique. Conditionally immortalized rat brain capillary endothelial cells were as an in vitro model of blood-brain barrier to examine the transport mechanism of imperatorin. Brain distribution volume of imperatorin was about 6 fold greater than that of sucrose, suggesting that the transport of imperatorin was through the blood-brain barrier in physiological state. Both in vivo and in vitro imperatorin transport studies demonstrated that imperatorin could be transported in a concentration-dependent manner with high affinity. Imperatorin uptake was dependent on proton gradient in an opposite direction. It was significantly reduced by pretreatment with sodium azide. However, its uptake was not inhibited by replacing extracellular sodium with potassium or N-methylglucamine. The uptake of imperatorin was inhibited by various cationic compounds, but not inhibited by TEA, choline and organic anion substances. Transfection of plasma membrane monoamine transporter, organic cation transporter 2 and organic cation/carnitine transporter 2/1 siRNA failed to alter imperatorin transport in brain capillary endothelial cells. Especially, tramadol, clonidine and pyrilamine inhibited the uptake of [$^3H$]imperatorin competitively. Therefore, imperatorin is actively transported from blood to brain across the blood-brain barrier by passive and carrier-mediated transporter.

• Archives of Pharmacal Research
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• 제27권2호
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• pp.127-135
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• 2004

Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities.

• BMB Reports
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• 제48권4호
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• pp.223-228
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• 2015

The Drosophila lymph gland is the hematopoietic organ in which stem-like progenitors proliferate and give rise to myeloid-type blood cells. Mechanisms involved in Drosophila hematopoiesis are well established and known to be conserved in the vertebrate system. Recent studies in Drosophila lymph gland have provided novel insights into how external and internal stresses integrate into blood progenitor maintenance mechanisms and the control of blood cell fate decision. In this review, I will introduce a developmental overview of the Drosophila hematopoietic system, and recent understandings of how the system uses developmental signals not only for hematopoiesis but also as sensors for stress and environmental changes to elicit necessary blood responses. [BMB Reports 2015; 48(4): 223-228]