• 제목/요약/키워드: Bcl-x

검색결과 331건 처리시간 0.039초

Kaempferol Activates G2-Checkpoint of the Cell Cycle Resulting in G2-Arrest and Mitochondria-Dependent Apoptosis in Human Acute Leukemia Jurkat T Cells

  • Kim, Ki Yun;Jang, Won Young;Lee, Ji Young;Jun, Do Youn;Ko, Jee Youn;Yun, Young Ho;Kim, Young Ho
    • Journal of Microbiology and Biotechnology
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    • 제26권2호
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    • pp.287-294
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    • 2016
  • The effect of kaempferol (3,5,7,4-tetrahydroxyflavone), a flavonoid compound that was identified in barnyard millet (Echinochloa crus-galli var. frumentacea) grains, on G2-checkpoint and apoptotic pathways was investigated in human acute leukemia Jurkat T cell clones stably transfected with an empty vector (J/Neo) or a Bcl-xL expression vector (J/Bcl-xL). Exposure of J/Neo cells to kaempeferol caused cytotoxicity and activation of the ATM/ATR-Chk1/Chk2 pathway, activating the phosphorylation of p53 (Ser-15), inhibitory phosphorylation of Cdc25C (Ser-216), and inactivation of cyclin-dependent kinase 1 (Cdk1), with resultant G2-arrest of the cell cycle. Under these conditions, apoptotic events, including upregulation of Bak and PUMA levels, Bak activation, mitochondrial membrane potential (Δψm) loss, activation of caspase-9, -8, and -3, anti-poly (ADP-ribose) polymerase (PARP) cleavage, and accumulation of apoptotic sub-G1 cells, were induced without accompanying necrosis. However, these apoptotic events, except for upregulation of Bak and PUMA levels, were completely abrogated in J/Bcl-xL cells overexpressing Bcl-xL, suggesting that the G2-arrest and the Bcl-xL-sensitive mitochondrial apoptotic events were induced, in parallel, as downstream events of the DNA-damage-mediated G2-checkpoint activation. Together these results demonstrate that kaempferol-mediated antitumor activity toward Jurkat T cells was attributable to G2-checkpoint activation, which caused not only G2-arrest of the cell cycle but also activating phosphorylation of p53 (Ser-15) and subsequent induction of mitochondria-dependent apoptotic events, including Bak and PUMA upregulation, Bak activation, Δψm loss, and caspase cascade activation.

유도 결합 플라즈마에 의해 식각된 ITO 특성 연구 (A Study of Etched ITO Characteristics by Inductively Coupled Plasma)

  • 위재형;김창일
    • 한국전기전자재료학회:학술대회논문집
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    • 한국전기전자재료학회 2010년도 하계학술대회 논문집
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    • pp.175-175
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    • 2010
  • The etching characteristics with etch rate of ITO thin films in an $O_2/BCl_3$/Ar plasma were investigated. The etch rate of ITO thin films increased with increasing $O_2$ content from 0 to 10 % in $BCl_3$/Ar plasma, whereas that of ITO decreased with increasing $O_2$ content from 10 % to 30 % in $BCl_3$/Ar plasma. The maximum etch rate of 65.9 nm/min for the ITO thin films was obtained at 10 % $O_2$ addition. The etch conditions were the RF power of 500 W, bias power of 200 W, and process pressure of 2 Pa. The analysis of x-ray photoelectron spectroscopy (XPS) was carried out to investigate the chemical reactions between the surfaces of ITO thin films and etch species.

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실리콘 기판위의 증착된 AAO Barrier Layer의 $Cl_2/BCl_3$ Neutral Beam Etching

  • 김찬규;민경석;오종식;염근영
    • 한국표면공학회:학술대회논문집
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    • 한국표면공학회 2011년도 춘계학술대회 및 Fine pattern PCB 표면 처리 기술 워크샵
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    • pp.135-136
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    • 2011
  • 본 연구에서는 실리콘 기판위의 형성된 AAO (Anodic Aluminum Oxide)의 barrier layer를 $Cl_2/BCl_3$ gas mixture에서 Neutral Beam Etching (NBE)과 Ion Beam Etching (IBE)로 각각 식각한 후 그 결과를 비교하였다. 이온빔의 경우 나노사이즈의 AAO pore의 charging에 의해 pore 아래쪽의 위치한 barrier layer를 어떤 식각조건에서도 제거하지 못하였다. 하지만, charging effect가 없고, 높은 중성화율을 나타내는 low angle forward reflected 방식의 neutral beam etching (NBE)에서는 $BCl_3$-rich $Cl_2/BCl_3$ gas mixture인 식각조건에서 AAO pore에 휘발성 $BO_xCl_y$를 형성하면서 barrier layer를 제거할 수 있었다.

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$BCl_3$/Ar 플라즈마에 따른 $TiO_2$ 박막의 식각 특성 (Etching Characteristics of $TiO_2$ Thin Film in $BCl_3$/Ar Plasma)

  • 주영희;우종창;박정수;허경무;김창일
    • 한국표면공학회:학술대회논문집
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    • 한국표면공학회 2009년도 추계학술대회 초록집
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    • pp.221-222
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    • 2009
  • 유도결합 플라즈마 (Inductively Coupled Plasma) 장비를 이용하여 각종 공정조건들에 따른 $TiO_2$의 식각 특성을 연구하였다. $BCl_3$/Ar 가스의 혼합비, 공정 압력 등을 공정 변수들로 정하였다. 공정 변수가 가스 혼합비일 경우 $BCl_3$ 가스의 비율이 25 % 일 경우 높은 식각률을 보였다. 또한 X-ray photoelectron spectroscopy를 이용하여 분석한 결과, $TiO_2$의 식각 메커니즘은 화학적인 영향보다는 물리적인 영향을 더 많이 받는다.

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Unlocking the Therapeutic Potential of BCL-2 Associated Protein Family: Exploring BCL-2 Inhibitors in Cancer Therapy

  • Bisan El Dakkak;Jalal Taneera;Waseem El-Huneidi;Eman Abu-Gharbieh;Rifat Hamoudi;Mohammad H. Semreen;Nelson C. Soares;Eman Y. Abu-Rish;Mahmoud Y. Alkawareek;Alaaldin M. Alkilany;Yasser Bustanji
    • Biomolecules & Therapeutics
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    • 제32권3호
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    • pp.267-280
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    • 2024
  • Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

Pb 함량에 따른 PZT 박막의 식각 및 유전특성에 관한 연구 (A study on the Etching and Dielectric Properties of PZT Thin Films with Excess Pb Contents)

  • 김경태;이성갑;김창일;이영희
    • 한국전기전자재료학회:학술대회논문집
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    • 한국전기전자재료학회 2000년도 춘계학술대회 논문집 전자세라믹스 센서 및 박막재료 반도체재료 일렉트렛트 및 응용기술
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    • pp.56-59
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    • 2000
  • In this study, Ferroelectric $Pb(Zr_x,Ti_{1-x})O_3$(x=0.53) thin films were fabricated by the spin-coating on the Pt/Ti/$SiO_2$/Si substrate using the PZT metal alkoxide solutions with various excess Pb contents. Etching of PZT film was performed using planar inductively coupled Ar(20)$/Cl_2/BCl_3$ plasma. The etch rate of PZT film was 2450 ${\AA}/min$ at Ar(20)$/BCl_3$(80) gas mixing ratio and substrate temperature of $80^{\circ}C$. The leakage current densities of before etching and after etching PZT thin film were $6.25\times10^{-8}A/cm^2$, $8.74\times10^{-7}A/cm^2$ with electric field of 0.07MV/em, respectively.

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A Conserved Mechanism for Binding of p53 DNA-Binding Domain and Anti-Apoptotic Bcl-2 Family Proteins

  • Lee, Dong-Hwa;Ha, Ji-Hyang;Kim, Yul;Jang, Mi;Park, Sung Jean;Yoon, Ho Sup;Kim, Eun-Hee;Bae, Kwang-Hee;Park, Byoung Chul;Park, Sung Goo;Yi, Gwan-Su;Chi, Seung-Wook
    • Molecules and Cells
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    • 제37권3호
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    • pp.264-269
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    • 2014
  • The molecular interaction between tumor suppressor p53 and the anti-apoptotic Bcl-2 family proteins plays an essential role in the transcription-independent apoptotic pathway of p53. In this study, we investigated the binding of p53 DNA-binding domain (p53DBD) with the anti-apoptotic Bcl-2 family proteins, Bcl-w, Mcl-1, and Bcl-2, using GST pull-down assay and NMR spectroscopy. The GST pull-down assays and NMR experiments demonstrated the direct binding of the p53DBD with Bcl-w, Mcl-1, and Bcl-2. Further, NMR chemical shift perturbation data showed that Bcl-w and Mcl-1 bind to the positively charged DNA-binding surface of p53DBD. Noticeably, the refined structural models of the complexes between p53DBD and Bcl-w, Mcl-1, and Bcl-2 showed that the binding mode of p53DBD is highly conserved among the anti-apoptotic Bcl-2 family proteins. Furthermore, the chemical shift perturbations on Bcl-w, Mcl-1, and Bcl-2 induced by p53DBD binding occurred not only at the p53DBD-binding acidic region but also at the BH3 peptide-binding pocket, which suggests an allosteric conformational change similar to that observed in Bcl-$X_L$. Taken altogether, our results revealed a structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins, which shed light on to the molecular understanding of the transcription-independent apoptosis pathway of p53.

위암의 BAD 단백질의 발현 (Immunohistochemical Analysis of BAD Protein Expression in Gastric Carcinomas)

  • 유남진;이종우;박원상;이정용;이석형
    • Journal of Gastric Cancer
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    • 제3권2호
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    • pp.75-79
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    • 2003
  • Purpose: Evidence exists that dysregulation of apoptosis is involved in the pathogenesis of cancer development. The Bcl-$x_{L}$/Bcl-2-associated death promoter (BAD), a member of the Bcl-2 family, is a critical regulatory component of the intrinsic cell-death pathway that exerts its pro-apoptotic effect upon heterodimerization with anti-apoptotic proteins Bcl-2 and Bcl-$X_{L}$. Expression of the BAD protein has been reported in several cancer types, but not in stomach cancer. The aim of this study was to explore the expression status of the BAD protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of the BAD protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the BAD protein in 57 ($95\%$) of the 60 cancers. Normal gastric mucosal cells showed weaker expressions of the BAD protein than gastric carcinomas. Conclusion: Taken together, these results suggest that stomach cancer cells in vivo may need BAD protein expression for apoptosis. Also, the higher expression of the BAD protein in stomach cancer cells than in normal gastric mucosal cells suggests that apoptosis might be easily triggered in susceptible stomach cancer cells, thereby producing selective pressure to make more apoptosis-resistant cells during tumor development.

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Removal of Anodic Aluminum Oxide Barrier Layer on Silicon Substrate by Using Cl2 BCl3 Neutral Beam Etching

  • 김찬규;연제관;민경석;오종식;염근영
    • 한국진공학회:학술대회논문집
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    • 한국진공학회 2011년도 제40회 동계학술대회 초록집
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    • pp.480-480
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    • 2011
  • 양극산화(anodization)는 금속을 전기화학적으로 산화시켜 금속산화물로 만드는 기술로서 최근 다양한 크기의 나노 구조를 제조하는 기술로 각광받고 있으며, 이러한 기술에 의하여 얻어지는 anodic aluminum oxide(AAO)는 magnetic data storage, optoelectronic device, sensor에 적용될 수 있는 nano device 뿐만 아니라 nanostructure를 제조하기 위한 template 및 mask로써 최근 광범위 하게 연구되고 있다. 또한, AAO는 Al2O3의 단단한 구조를 가진 무기재료이므로 solid mask로써 다른 porous materials 보다 뛰어난 특성을 갖고 있다. 또한 electron-beam lithography 및 block co-polymer 에 의한 patterning 과 비교하여 매우 경제적이며, 재현성이 우수할 뿐만 아니라 대면적에서 나노 구조의 크기 및 형상제어가 비교적 쉽기 때문에 널리 사용되고 있다. 그러나, AAO 형성 시 생기게 되는 반구형 모양의 barrier layer는 물질(substance)과 기판과의 direct physical and electrical contact을 방해하기 때문에 해결해야 할 가장 큰 문제점 중 하나로 알려져 있다. 따라서 본 연구에서는 실리콘 기판위의 형성된 AAO의 barrier layer를 Cl/BCl3 gas mixture에서 Neutral Beam Etching (NBE)과 Ion Beam Etching (IBE) 로 각각 식각한 후 그 결과와 비교하였다. NBE와 IBE 모두 Cl2/BCl3 gas mixture에서 BCl3 gas의 첨가량이 60% 일 경우 etch rate이 가장 높게 나타났고, optical emission spectroscopy (OES)로 Cl2/BCl3 플라즈마 내의 Cl radical density와 X-ray photoelectron spectroscopy (XPS)로 AAO 표면 위를 관찰한 결과 휘발성 BOxCly의 형성이 AAO 식각에 크게 관여함을 확인 할 수 있었다. 또한, NBE와 IBE 실험한 다양한 Cl2/BCl3 gas mixture ratio 에서 AAO가 식각이 되지만, 이온빔의 경우 나노사이즈의 AAO pore의 charging에 의해 pore 아래쪽의 위치한 barrier layer를 어떤 식각조건에서도 제거하지 못하였다. 하지만, NBE에서는 BCl3-rich Cl2/BCl3 gas mixture인 식각조건에서 AAO pore에 휘발성 BOxCly를 형성하면서 barrier layer를 제거할 수 있었다.

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Bcl-2 및 IAP family의 발현 변화와 caspase 활성을 통한 봉독의 인체폐암세포 apoptosis 유도 (Induction of Apoptosis by Bee Venom in A549 Human Lung Epithelial Cancer Cells through Modulation of Bcl-2 and IAP Family and Activation of Caspases)

  • 우현주;김현중;홍수현;홍상훈;최병태;이용태;박동일;최영현
    • 생명과학회지
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    • 제17권11호
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    • pp.1596-1600
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    • 2007
  • 본 연구에서 봉독의 apoptosis 유도에 의한 항암기전 효능을 A549 인체폐암세포를 대상으로 조사하였으며, apoptosis 유발에 관여할 것으로 예상되는 중요한 유전자들의 발현 및 활성에 미치는 봉독의 영향을 조사하였다. A549 세포의 생존율은 봉독의 처리 농도 증가에 따라 강력하게 억제되었으며, 이는 염색질 응축 현상을 동반한 apoptosis 유발에 의한 것임을 알 수 있었다. 봉독 처리에 의한 apoptosis 유발은 Bax 및 Bcl-xL의 발현 변화 없이 Bcl-2의 발현 감소에 따른 상대적인 Bax의 발현 증가와 IAP family에 속하는 인자들의 발현 감소 및 caspase의 활성화와 연관성이 있었다.