• 제목/요약/키워드: Target degradation

검색결과 358건 처리시간 0.026초

길경이 인체 폐암세포에 미치는 영향에 대한 실험적 연구 (Apoptotic Cell Death of Human Lung Carcinoma A549 Cells by an Aqueous Extract from the Roots of Platycodon grandiflorum)

  • 이성열;김원일;박동일
    • 동의생리병리학회지
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    • 제17권4호
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    • pp.1019-1030
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    • 2003
  • Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the growth of human lung carcinoma A549 cells. Results obtained are as fellow; AEPG treatment resulted in the inhibition of the cell viability of A549 cells in a concentration-dependent manner. Upon treatment with AEPG, A549 cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that AEPG increased populations of apoptotic-sub G1 phase. Western blot and RT-PCR analyses indicated that the expressions of Bcl-2 was down-regulated but Bax was up-regulated in AEPG-treated A549 cells. AEPG-induced apoptotis of A549 cells was associated with rroteolytic cleavage and activation of caspase-3, release of cytochrome c from mitochondria into cytosol and down-regulation of Akt and phospho-Akt proteins in a dose-dependent manner. Induction of apoptosis by AEPG treatment was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ 1. AEPG treatment inhibited the levels of cyclooxygenases protein of A549 cells, which was associated with the inhibition of prostaglandin E2 accumulation in a concentration-dependent fashion. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

Expressed Sequence Tag Analysis of the Erythrocytic Stage of Plasmodium berghei

  • Seok, Ji-Woong;Lee, Yong-Seok;Moon, Eun-Kyung;Lee, Jung-Yub;Jha, Bijay Kumar;Kong, Hyun-Hee;Chung, Dong-Il;Hong, Yeon-Chul
    • Parasites, Hosts and Diseases
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    • 제49권3호
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    • pp.221-228
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    • 2011
  • Rodent malaria parasites, such as Plasmodium berghei, are practical and useful model organisms for human malaria research because of their analogies to the human malaria in terms of structure, physiology, and life cycle. Exploiting the available genetic sequence information, we constructed a cDNA library from the erythrocytic stages of P. berghei and analyzed the expressed sequence tag (EST). A total of 10,040 ESTs were generated and assembled into 2,462 clusters. These EST clusters were compared against public protein databases and 48 putative new transcripts, most of which were hypothetical proteins with unknown function, were identified. Genes encoding ribosomal or membrane proteins and purine nucleotide phosphorylases were highly abundant clusters in P. berghei. Protein domain analyses and the Gene Ontology functional categorization revealed translation/protein folding, metabolism, protein degradation, and multiple family of variant antigens to be mainly prevalent. The presently-collected ESTs and its bioinformatic analysis will be useful resources to identify for drug target and vaccine candidates and validate gene predictions of P. berghei.

Joint Crediting Mechanism under the Paris Agreement and Its Implication to the Climate Policy in Korea

  • Jung, Tae Yong;Sohn, Jihyun
    • 한국기후변화학회지
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    • 제7권4호
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    • pp.373-381
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    • 2016
  • Before the Conference of Parties (COP) 21 of the United Nations Framework Convention on Climate Change (UNFCCC) in 2015, most parties of UNFCCC had submitted their intended nationally determined contributions (INDCs) and to achieve their voluntary targets, some parties consider using international market mechanisms. As one of such mechanisms, Japan promoted its own bilateral mechanism called Joint Crediting Mechanism (JCM). In this study, feasibility studies and projects under JCM have been analyzed by project type, sector, country and region, which could provide some implications in designing Korea's future climate policy to achieve Korea's targets of 11.7% using international market mechanism in INDC. Since 2010, JCM has promoted 542 projects and feasibility studies in 44 countries according to the Institute for Global Environmental Strategies (IGES) database. Among 542 projects, about 80% were feasibility studies implying that JCM was more focused on project identification. However, current trends of JCM show that more projects will be soon implemented based on these feasibility studies. For sectoral categorization, projects were categorized into seven sectors-energy technology, energy efficiency, renewable energy, waste management, city, strategic planning and projects related to the country's efforts to reduce emissions from deforestation and forest degradation (REDD+). JCM projects were mitigation focused with more than 70% of projects were related to energy efficiency, renewable energy and energy technology. At the regional and country level, JCM is highly focused on Asia and especially, more than 100 projects were developed in Indonesia. Based on the analysis of JCM, in order to develop bilateral international mechanism for Korea, it is worthwhile to emphasize that Korea considers Asian countries as her partner. In addition, Korea may consider the collaboration with Multilateral Development Banks (MDBs) to implement projects identified by Korea and Asian partner countries. Furthermore, strategically, it is recommendable to develop jointly with Japan who has already capacity and networks with other Asian countries to mitigate GHG emissions. Such financial resources from MDBs and Japan may contribute to meet the 11.3% of GHG reduction target from abroad according to INDC of Korea.

경계(警戒) 임무(任務) 담당자(擔當者)의 시간지연(時間遲延)에 따르는 인간(人間) 성능(性能)의 변화(變化)에 대(對)한 연구(硏究) 및 개선방안(改善方案) (The Human Performance Degradation in Vigilance due to Prolonged and Monotonous Tasks)

  • 이면우
    • 대한조선학회지
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    • 제11권1호
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    • pp.27-34
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    • 1974
  • This study is aimed at a validation of the vigilance simulation model which was proposed earlier (2). The model estimates a perceived danger value, an alertness level and the probability of detection at a given elapsed time of vigilance. Twenty-nine male and seven female subjects were given a simple task. They were asked to detect a number(four numbers out of six digits in the telephone directory which have the probability of occurrence in the range of 0.0010-0.0018) in six different experimental conditions, for periods of two to three hours. Analysis of the experiments showed that although the mean detection rate varied slightly in two hours, the within-subject variance and the number of cyclic performance fluctuations increased significantly. A primal factor that affects the performance seems to be the frequency of target occurrence. By curve fitting, the relation between the probability of detection and the percentages of danger event occurrence was derived; $y=0.50(1-{\varepsilon}^{-50x^2})+0.39$. Assuming the equation represents the normal detection rate(100% performance), the Relative Vigilance Performance Rating was calculated. This rating method could be a useful criterion in selecting and training of the vigilance personnel. The results show that the simulation model is a good estimator of human a performance when the probability of danger occurrence is greater than 0.0015; it gives a good reference for improving the vigilance system. Suggestions are made that (1) the validity of proposed functional equations over the extended range of danger probability be studied, (2) an analysis of the cyclic fluctuations of the alertness level be accomplished, and (3) the cost functions of detection reliability be included in any future model.

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Suppression of Protein Kinase C and Nuclear Oncogene Expression as Possible Action Mechanisms of Cancer Chemoprevention by Curcumin

  • Lin, Jen-Kun
    • Archives of Pharmacal Research
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    • 제27권7호
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    • pp.683-692
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    • 2004
  • Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

Dephosphorylation of p53 Ser 392 Enhances Trimethylation of Histone H3 Lys 9 via SUV39h1 Stabilization in CK2 Downregulation-Mediated Senescence

  • Park, Jeong-Woo;Bae, Young-Seuk
    • Molecules and Cells
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    • 제42권11호
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    • pp.773-782
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    • 2019
  • Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKT-mTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53-dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, $p21^{Cip1/WAF1}$ is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of $p21^{Cip1/WAF}$. Taken together, these results suggest that CK2 downregulation induces dephosphorylation of Ser 392 on p53, which subsequently increases the stability of SUV39h1 and the expression of $p21^{Cip1/WAF1}$, leading to H3K9me3 and SAHFs formation.

Biphasic Regulation of Mitogen-Activated Protein Kinase Phosphatase 3 in Hypoxic Colon Cancer Cells

  • Kim, Hong Seok;Kang, Yun Hee;Lee, Jisu;Han, Seung Ro;Kim, Da Bin;Ko, Haeun;Park, Seyoun;Lee, Myung-Shin
    • Molecules and Cells
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    • 제44권10호
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    • pp.710-722
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    • 2021
  • Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.

Parallel Computing on Intensity Offset Tracking Using Synthetic Aperture Radar for Retrieval of Glacier Velocity

  • Hong, Sang-Hoon
    • 대한원격탐사학회지
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    • 제35권1호
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    • pp.29-37
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    • 2019
  • Synthetic Aperture Radar (SAR) observations are powerful tools to monitor surface's displacement very accurately, induced by earthquake, volcano, ground subsidence, glacier movement, etc. Especially, radar interferometry (InSAR) which utilizes phase information related to distance from sensor to target, can generate displacement map in line-of-sight direction with accuracy of a few cm or mm. Due to decorrelation effect, however, degradation of coherence in the InSAR application often prohibit from construction of differential interferogram. Offset tracking method is an alternative approach to make a two-dimensional displacement map using intensity information instead of the phase. However, there is limitation in that the offset tracking requires very intensive computation power and time. In this paper, efficiency of parallel computing has been investigated using high performance computer for estimation of glacier velocity. Two TanDEM-X SAR observations which were acquired on September 15, 2013 and September 26, 2013 over the Narsap Sermia in Southwestern Greenland were collected. Atotal of 56 of 2.4 GHz Intel Xeon processors(28 physical processors with hyperthreading) by operating with linux environment were utilized. The Gamma software was used for application of offset tracking by adjustment of the number of processors for the OpenMP parallel computing. The processing times of the offset tracking at the 256 by 256 pixels of window patch size at single and 56 cores are; 26,344 sec and 2,055 sec, respectively. It is impressive that the processing time could be reduced significantly about thirteen times (12.81) at the 56 cores usage. However, the parallel computing using all the processors prevent other background operations or functions. Except the offset tracking processing, optimum number of processors need to be evaluated for computing efficiency.

물리서식처 모의를 이용한 구하도 복원이 피라미의 서식처에 미치는 영향 평가: 청미천 연구 사례 (Evaluation of the Impact of Abandoned Channel Restoration on Zaco platypus habitat using the Physical Habitat Simulation: A Case Study of the Cheongmi-cheon Stream in Korea)

  • 김승기;최성욱
    • Ecology and Resilient Infrastructure
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    • 제6권2호
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    • pp.101-108
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    • 2019
  • 본 연구에서는 물리서식처 분석을 이용하여 구하도 복원에 따른 어류서식처의 영향을 분석하였다. 연구대상지역은 청미천의 1.2 km 구간이다. 연구 대상 지역에서 구하도 복원은 2012년 7월 부터 2015년 12월 까지 수행되었다. 복원 전과 후에 대하여 물리서식처 분석을 실시하였다. 이때, 수리해석을 River2D 모형을 이용하였으며 서식처분석을 위하여 서식처 적합도 지수 곡선을 이용하였다. 대상어종은 연구대상지역의 우점종인 피라미를 선정하였다. 복원 전과 후의 조건에 대하여 다양한 유량에 대하여 수리해석을 실시하였다. 이후 구하도가 복원 되기 전과 후의 조건에서 복합 서식처 적합도 지수와 가중가용면적을 계산하였으며, 피라미의 물리서식처 변화에 대하여 분석하였다. 모의 결과 구하도가 복원될 경우 어류의 서식처 영역이 증가되었으며, 큰 유량에 대하여 서식처의 감소를 방지하는데 효과가 있음을 확인하였다.

Mechanisms for Hfq-Independent Activation of rpoS by DsrA, a Small RNA, in Escherichia coli

  • Kim, Wonkyong;Choi, Jee Soo;Kim, Daun;Shin, Doohang;Suk, Shinae;Lee, Younghoon
    • Molecules and Cells
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    • 제42권5호
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    • pp.426-439
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    • 2019
  • Many small RNAs (sRNAs) regulate gene expression by base pairing to their target messenger RNAs (mRNAs) with the help of Hfq in Escherichia coli. The sRNA DsrA activates translation of the rpoS mRNA in an Hfq-dependent manner, but this activation ability was found to partially bypass Hfq when DsrA is overproduced. The precise mechanism by which DsrA bypasses Hfq is unknown. In this study, we constructed strains lacking all three rpoS-activating sRNAs (i.e., ArcZ, DsrA, and RprA) in $hfq^+$ and $Hfq^-$ backgrounds, and then artificially regulated the cellular DsrA concentration in these strains by controlling its ectopic expression. We then examined how the expression level of rpoS was altered by a change in the concentration of DsrA. We found that the translation and stability of the rpoS mRNA are both enhanced by physiological concentrations of DsrA regardless of Hfq, but that depletion of Hfq causes a rapid degradation of DsrA and thereby decreases rpoS mRNA stability. These results suggest that the observed Hfq dependency of DsrA-mediated rpoS activation mainly results from the destabilization of DsrA in the absence of Hfq, and that DsrA itself contributes to the translational activation and stability of the rpoS mRNA in an Hfq-independent manner.