• 생명과학회지
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• 제13권1호
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• pp.118-127
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• 2003

Phenylalanine의 구조유사체인 p-fluotophenylalanine (FPA)은 인체 급성백혈병세포주인 Jurkat T 세포의 세포자살을 유도한다. FPA에 의한 세포자살에 미치는 Bcl-2 또는 Bcl-xL의 영향을 조사하기 위해, Bcl-2 또는 Bcl-xL을 stable transfection하거나 empty vectors만을 Transfection한 Jurkat 세포를 이용하여 FPA의 세포독성과 FPA에 의한 세포내 세포자살 신호전달경로를 비교 분석하였다. Jurkt T 세포에 0.63∼3.0 mLf의 FPA를 처리하였을 때 세포의 생육도는 농도에 비례하여 감소하였다. 또한 세포자살관련 DNA fragmentation, caspase-8 activatoin, Bid cleavage, mitochondria로 부터의 cytochrome c 방출, caspase-9 및 -3 activation, PARP degradation 등이 유도되었다. 한편, FPA에 의해 유도되는 이러한 일련의 생화학적 현상들은 Bcl-2 또는 Bcl-xL의 overexpression에 의해 현저히 저해되었다. 이상의 결과들은 caspase-8 activation, Bid cleavage, mitochondnal cytochrome c 방출에 의해 활성화되는 casuase cascade 등의 현상이, Bcl-2 또는 Bcl-xL에 의해 억제됨을 나타내며 FPA에 의해 유도되는 세포자살에 필요한 과정임을 시사한다.

• Journal of Microbiology and Biotechnology
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• 제12권6호
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• pp.950-956
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• 2002

The antitumor activity of the insect pathogenic fungus Paecilomyces japonica has been attributed to apoptotic cell death. However, the mechanism underlying the induced apoptosis has not yet been elucidated. In this study, we for the first time show that mitochondria-dependent caspase-3 activation were associated with the apoptotic activity of P. japonica in human acute leukemia Jurkat T cells. When Jurkat T cells were treated with the ethyl acetate extract of P japonica at concentrations ranging from $2-6{\mu}g/ml$, apoptotic cell death. accompanied by several biochemical events such as caspase-9 activation, caspase-3 activation, degradation of poly (ADP-ribose) polymerase (PARP), and apoptotic DNA fragmentation, was induced in a dose-dependent manner. In addition, the release of cytochrome c from mitochondria was detected. Under these conditions, the expression of Fas and Fas-ligand (FasL) remained unchanged. Ethyl acetate extract-induced mitochondrial cytochrome c release, caspase-3 activation, PARP cleavage, and apoptotic DNA fragmentation were suppressed by the ectopic expression of Bcl-2, which is known to block mitochondrial cytochrorme c release. Accordingly, these results demonstrate that P. japonica-induced apoptotic cell death is mediated by a cytochrome c-dependent caspase-3 activation pathway that can be interrupted by Bcl-2.

• IMMUNE NETWORK
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• 제13권5호
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• pp.213-217
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• 2013

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the ${\beta}$-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (${\beta}$-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the ${\beta}$-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.

• Fisheries and Aquatic Sciences
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• 제19권9호
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• pp.35.1-35.6
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• 2016

Gliotoxin has been recognized as an immunosuppressive agent for a long time. Recently, it was reported to have antitumor properties. However, the mechanisms by which it inhibits tumors remain unclear. Here, we showed that gliotoxin isolated from the marine fungus Aspergillus fumigatus inhibited proliferation and induced apoptosis in HT1080 human fibrosarcoma cells. Gliotoxin repressed phosphorylation-dependent degradation of $I{\kappa}B-{\alpha}$, an antagonist of nuclear factor kappa B ($NF-{\kappa}B$), which is a known tumor-promoting factor. This coincided with a decrease in nuclear import of $NF-{\kappa}B$, suggesting its signaling activity was impaired. Moreover, gliotoxin increased intracellular reactive oxygen species (ROS). Since ROS have been known to inhibit $NF-{\kappa}B$, this may also contribute to gliotoxin's antitumorigenic effects. These results suggest that gliotoxin suppressed the activation of $NF-{\kappa}B$ by inhibiting phosphorylation and degradation of $I{\kappa}B-{\alpha}$ and by increasing ROS, which resulted in apoptosis of HT1080 cells. Cumulatively, gliotoxin is a promising candidate antagonist of $NF-{\kappa}B$, and it should be investigated for its possible use as a selective inhibitor of human fibrosarcoma cells.

• 한국산업정보학회논문지
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• 제18권6호
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• pp.25-30
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• 2013

나노크기 MOSFET 공정에서 회로의 신뢰도에 영향을 미치는 음 바이어스 온도 불안정성(NBTI), 핫 캐리어 주입(HCI), 시간 의존 유전체 파손(TDDB) 등과 같은 노화 현상들에 의해서 회로 성능의 심각한 저하를 가져올 수 있다. 그러므로, 본 논문에서는 디지털회로에서 발생할 수 있는 노화를 극복할 수 있는 적응형 보상 회로를 제안하고자 한다. 제안된 보상회로는 노화에 의해 감소하는 회로 성능을 적응적으로 보상해 주기 위해서 노화 정도에 따라 파워스위치 폭을 조절할 수 있고, 순방향 바디 바이어싱 전압을 걸어줄 수 있는 파워 게이팅 구조를 사용하여서 45nm의 공정기술에서 설계되었다.

• Earthquakes and Structures
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• 제3권5호
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• pp.649-673
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• 2012

Recent studies have highlighted the importance of accounting for aging and deterioration of bridges when estimating their seismic vulnerability. Effects of structural degradation of multiple bridge components, variations in bridge geometry, and comparison of different environmental exposure conditions have traditionally been ignored in the development of seismic fragility curves for aging concrete highway bridges. This study focuses on the degradation of multiple bridge components of a geometrically varying bridge class, as opposed to a single bridge sample, to arrive at time-dependent seismic bridge fragility curves. The effects of different exposure conditions are also explored to assess the impact of severity of the environment on bridge seismic vulnerability. The proposed methodology is demonstrated on a representative class of aging multi-span reinforced concrete girder bridges typical of the Central and Southeastern United States. The results reveal the importance of considering multiple deterioration mechanisms, including the significance of degrading elastomeric bearings along with the corroding reinforced concrete columns, in fragility modeling of aging bridge classes. Additionally, assessment of the relative severity of exposure to marine atmospheric, marine sea-splash and deicing salts, and shows 5%, 9% and 44% reduction, respectively, in the median value bridge fragility for the complete damage state relative to the as-built pristine structure.

• KSBB Journal
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• 제8권5호
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• pp.424-430
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• 1993

생체에 스트레스가 부하되였을 때의 각종 상해작 용을 경감사키는 목적으로 Vitamin C를 투여하여 in vitro 및 in vivo 설험을 수행하여 살펴 본 결과, 시험관 내에셔 ascorbic acid는 $Cu^{2+}$ 이온의 존재 하에셔 histamine을 농도 의존적으로 분해하였고 반 응시간이 걸어질수록 histamine의 분해가 촉진되었 으며, histamine 첨가에 의해서도 ascorbic acid가 분해되는 이른바 in vitro 상호분해작용을 나타냈다. 또한 유전적으로 Vitamin C 합성볼능으로 알려져 있는 $ODS^{od}/_{od}$ rat를 이용하여 Vitamin C 결핍사료 를 급여한 후에 ascorbic acid의 첨가(50mgjlOOg B B. W.)는 histamine의 뇨중 배설을 유의성 있게 감 소시켰다. 부신을 적출한 rat에 immobilization s stress를 부하하기 전에 ascorbic acid, 인공의 glucocorticoid 인 dexamethasone 빛 histamine HI -길항제 인 promethazine을 투여하면 stress에 의한 치사작용이 완전히 억제되었으나, OH radical sca­v venger언 dimethylsul[ oxide는 억제작용을 보이지 않았으며, $ODS^{od}/_{od}$ rat의 비장세포 배양계를 이용한 Con A 의존성 T엄파구의 증식능에 있어서는 10^{-8}- 1O^{-5}M$의 ascorbic acid 첨가에 의하여 유의성 있게 증가되였다. 이러한 결과는 Vitamin C가 스트레스에 의한 각 종 상해작용을 경감시키는 능력을 가지고 있음을 나 타내고 었으며, 이것은 스트레스 반응응답기전의 매개물질의 하나로 알려 져 있는 histamine을 Vitamin C가 분해시킴으로써 항스트레스 효과가 발현되는 것 으로 추정된다. 또한 Vitamin C 자신은 체내의 면 역능력을 증강시키는 작용도 가지고 있는 것으로 시 사된다.

• 한국동물학회지
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• 제36권3호
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• pp.342-346
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• 1993

배양 근원세포의 세포 골격 단백질의 양이 분화과정에 따라 점차 감소하는 것으로 나타났다. 이러한 세포 골격 단백질의 분해는, 세포막에 투과성을 나타내는 calpain의 저해제인 calpeptin의 처리에 의하여 억제될 수 있었다. 또한, calpeptin은 특정 세포 골격 단백질의 분해를 제한적으로 억제하였으나, 전체적인 세포 단백질의 양상에는 별 영향을 주지 않았다. 뿐만 아니라, calpeptin은 농도 의존적으로 근원세포의 융합을 억제하였다. 반면에, calpain의 강력한 저해제이지만 세포막에 투과성을 보이지 않는 E-64는 세포 골격 단백질의 분해와 막 융합에 아무런 효과를 나타내지 못하였다. 이러한 결과는 calpain이 근세포 분화 시기에 따라 세포 골격 단백질의 분해를 촉매하며, 이 분해 과정은 근원세포 융합에 필연적인 것으로 추측된다. 또한, 이 결과는 calpain 저해제들의 선별적 효과가 그들의 세포막에 대한 투과성에 기인함을 시사한다.

• 한국발생생물학회지:발생과생식
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• 제18권4호
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• pp.225-231
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• 2014

Autophagy is a homeostatic degradation process that is involved in tumor development and normal development. Autophagy is induced in cancer cells in response to chemotherapeutic agents, and inhibition of autophagy results in enhanced cancer cell death or survival. Chloroquine (CQ), an anti-malarial drug, is a lysosomotropic agent and is currently used as a potential anticancer agent as well as an autophagy inhibitor. Here, we evaluate the characteristics of these dual activities of CQ using human colorectal cancer cell line HCT15. The results show that CQ inhibited cell viability in dose- and time-dependent manner in the range between 20 to 80 uM, while CQ did not show any antiproliferative activity at 5 and 10 uM. Cotreatment of CQ with antitumor agent NVP-BEZ235, a dual inhibitor of PI3K/mTOR, rescued the cell viability at low concentrations meaning that CQ acted as an autophagy inhibitor, but CQ induced the lethal effect at high concentrations. Acridine orange staining revealed that CQ at high doses induced lysosomal membrane permeabilization (LMP). High doses of CQ produced cellular reactive oxygen species (ROS) and cotreatment of antioxidants, such as NAC and trolox, with high doses of CQ rescued the cell viability. These results suggest that CQ may exert its dual activities, as autophagy inhibitor or LMP inducer, in concentration-dependent manner.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권1호
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• pp.20-27
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• 2007

Eugenol is commonly used in dentistry for the sedation of toothache, pulpitis, and dental hyperalgesia. This study was performed to investigate the apoptotic effect of eugenol to human osteosarcoma (HOS) cells and the potential use of this compound in osteosarcoma cells. Eugenol showed the apoptotic effect in HOS cells in dose- and time-dependent manner. Fragmentation and condensation of DNA were showed by TUNEL assay, Hemacolor stain and Hoechst stain. In the DNA electrophoresis analysis, cells showed DNA degradation characteristic of apoptosis with a ladder pattern of DNA fragments. Apoptosis-related factors were analyzed by western blotting. Cells treated with eugenol showed caspase-3, PARP, lamin A and DFF-45 cleavage. Eugenol treatment induced caspase-3 cleavage and activation. Cleavages of PARP, DFF-45 and lamin A were accompanied with activation of caspase triggered by eugenol in HOS cells. Though this study needs more investigations, these results suggest that eugenol induce apoptosis via caspase dependent pathway in HOS cells and eugenol may constitute a potential antitumor compound against osteosarcoma cells.