• Title/Summary/Keyword: c-Jun degradation

Search Result 236, Processing Time 0.023 seconds

Apoptotic Effect of Co-Treatment with Valproic Acid and 17AAG on Human Osteosarcoma Cells (Valproic acid와 17AAG의 병용처리가 사람골육종세포에 미치는 세포자멸사 효과에 대한 연구)

  • Park, Jun-Young;Park, Se-Jin;Kim, In-Ryoung;Park, Bong-Soo;Jeong, Sung-Hee;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
    • /
    • v.36 no.1
    • /
    • pp.11-20
    • /
    • 2011
  • Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

The change of grain quality and starch assimilation of rice under future climate conditions according to RCP 8.5 scenario (RCP 8.5 시나리오에 따른 미래 기후조건에서 벼의 품질 및 전분 동화 특성 변화)

  • Sang, Wan-Gyu;Cho, Hyeoun-Suk;Kim, Jun-Hwan;Shin, Pyong;Baek, Jae-Kyeong;Lee, Yun-Ho;Cho, Jeong-Il;Seo, Myung-Chul
    • Korean Journal of Agricultural and Forest Meteorology
    • /
    • v.20 no.4
    • /
    • pp.296-304
    • /
    • 2018
  • The objective of this study was to analyze the impact of climate change on rice yield and quality. Experiments were conducted using SPAR(Soil-Plant-Atmosphere-Research) chambers, which was designed to create virtual future climate conditions, in the National Institute of Crop Science, Jeonju, Korea, in 2016. In the future climate conditions($+2.8^{\circ}C$ temp, 580 ppm $CO_2$) of year 2051~2060 according to RCP 8.5 scenario, elevated temperature and $CO_2$ accelerated the heading date by about five days than the present climate conditions, resulted in a high temperature environment during grain filling stage. Rice yield decreased sharply in the future climate conditions due to the high temperature induced poor ripening. And the spikelet numbers, ripening ratio, and 1000-grain weight of brown rice were significantly decreased compared to control. The rice grain quality was also decreased sharply, especially due to the increased immature grains. In the future climate conditions, expression of starch biosynthesis-related genes such as granule-bound starch synthase(GBSSI, GBSSII, SSIIa, SSIIb, SSIIIa), starch branching enzyme(BEIIb) and ADP-glucose pyrophosphorylase(AGPS1, AGPS2, AGPL2) were repressed in developing seeds, whereas starch degradation related genes such as ${\alpha}-amylase$(Amy1C, Amy3D, Amy3E) were induced. These results suggest that the reduction in yield and quality of rice in the future climate conditions is likely caused mainly by the poor grain filling by high temperature. Therefore, it is suggested to develop tolerant cultivars to high temperature during grain filling period and a new cropping system in order to ensure a high quality of rice in the future climate conditions.

Anti-inflammatory effect of Sinhyowoldo-san Extract with regard to Pro-inflammatory Mediators in PMA plus A23187-induced Human Mast Cells (인간 비만세포에서 PMA와 A23187에 의해 유도된 전염증 매개체에 대한 신효월도산 추출물의 항염증 효과)

  • Wi, Gyeong;Yang, Da-Wun;Kang, Ok-Hwa;Kim, Sung-Bae;Mun, Su-Hyun;Seo, Yun-Soo;Kang, Da-Hye;Lim, Jae-Soo;Kim, Ma-Ryong;Kwak, Nam-Won;Kong, Ryong;Kwon, Dong-Yeul
    • The Korea Journal of Herbology
    • /
    • v.29 no.6
    • /
    • pp.117-123
    • /
    • 2014
  • Objectives : Sinhyowoldo-san (SHWDS) is said to be a traditional medicine used for shigellosis, abdominal pain, diarrhea. But mechanism of SHWDS mediated-modulation of immune function is not sufficiently understood. To ascertain the molecular mechanisms of SHWDS 70% EtOH extract on pharmacological and biochemical actions in inflammation, we researched the effect of pro-inflammatory mediators in phorbol-12-myristate-13-acetate (PMA)+ A23187-activated human mast cell line (HMC-1). Methods : In the present research, cell viability was measured by MTS assay. pro-inflammatory cytokine production was measured by performing enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR), and western blot analysis to analyze the activation of mitogen-activated protein kinases (MAPKs), nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). The investigation focused on whether SHWDS inhibited the expressions of interleukin-6 (IL-6), interleukin-8 (IL-8), MAPKs and $NF-{\kappa}B$ in PMA+A23187-activated HMC-1 cells. Results : SHWDS has no cytotoxicity at measured concentration (50, 100, and $250{\mu}g/ml$). SHWDS ($250{\mu}g/ml$) inhibits pro-inflammatory cytokine expression in PMA+ A23187-activated HMC-1 cells. Moreover, SHWDS inhibited cyclooxygenase (COX)-2 expression. In activated HMC-1 cells, SHWDS suppressed phosphorylation of extracellular signal-regulated kinase (ERK 1/2) and c-jun N-terminal Kinase (JNK 1/2). Then, SHWDS suppressed activation of nuclear factor $NF-{\kappa}B$ in nuclear, degradation of IkB ${\alpha}$ in cytoplasm. Conclusions : We propose that SHWDS has an anti-inflammatory therapeutic potential, which may result from inhibition of ERK 1/2, JNK 1/2 phosphorylation and $NF-{\kappa}B$ activation, thereby decreasing the expression of pro-inflammatory genes.

Changes in Quality of Pork Meat Seasoned with Red Wine during Storage (레드와인을 첨가한 양념돈육의 저장 중 품질 변화)

  • Lee, Kyung-Soo;Park, Kyung-Suk;Park, Hyun-Suk;Choi, Young-Jun;Park, Sung-Sook;Jung, In-Chul;Moon, Yoon-Hee
    • Journal of the East Asian Society of Dietary Life
    • /
    • v.21 no.1
    • /
    • pp.74-81
    • /
    • 2011
  • This study was carried out to investigate the effect of red wine on the color, hardness, springiness, chewiness, pH, volatile basic nitrogen (VBN) content, thiobarbituric acid reactive substances (TBARS) value, and total bacterial number of pork meat stored at $4^{\circ}C$ for 10 days. Pork meat was treated with 25% water (control), 20% water and 5% red wine (RW5), 15% water and 10% red wine (RW10), or 10% water and 15% red wine (RW15). The lightness ($L^*$), redness ($a^*$) and yellowness ($b^*$) values tended to decrease with longer storage period (p<0.05). The $L^*$ values of RW10 and RW15 were higher than those of control and RW5 on the first day of storage, whereas the control and RW5 had higher $L^*$ values compared to RW10 and RW15 after 10 days (p<0.05). Hardness of RW5 was the lowest after 10 days of storage (p<0.05). The pH levels were not significantly different among the samples. The VBN contents increased with longer storage period (p<0.05), and those of RW10 and RW15 were lower than those of the control and RW5 after 10 days of storage (p<0.05). The TBARS values increased with longer storage period (p<0.05), and those of the control, RW5, RW10, and RW15 were 0.61, 0.45, 0.35 and 0.33 mg MA/kg, respectively, after 10 days of the storage. The total bacterial numbers increased with longer storage period, and those of RW5, RW10 and RW15 were lower compared to the control (p<0.05). Taste, tenderness, juiciness, and palatability were not significantly different among the samples, but the flavor of RW5 had the highest value after 10 days of storage (p<0.05). These results suggest that red wine can inhibit protein degradation, lipid oxidation, and bacterial growth when used as an additive of seasoned pork meat.

Degradation evaluation of paint films on surface treated steel by electrochemical impedance spectroscopy (전기화학적 임피던스 분광법에 의한 표면처리한 강재 도장의 부식-도막 열화도 평가)

  • Park, Jun-Mu;Park, Jae-Hyeok;Kim, Sun-Ho;U, Sang-Gyun;Gwon, Yong-Min;Mun, Gyeong-Man;Lee, Myeong-Hun
    • Proceedings of the Korean Institute of Surface Engineering Conference
    • /
    • 2018.06a
    • /
    • pp.95-95
    • /
    • 2018
  • 강재의 방식법 중 도장은 부식을 억제하는데 효과적이고 편리한 방법으로 선박 및 해양 강 구조물의 방식법으로 사용되고 있다. 한편, 강 구조물의 효율적인 유지관리를 위해서는 방식 도장의 도막 열화도를 평가하고 잔존 수명을 예측하여 최적 시기에 보수도장 혹은 재도장하는 것이 필요하다. 일반적으로 선박 및 해양구조물에 적용되는 도막의 방식 성능 평가 방법으로 해수 침지 시험, 염수 분무 시험, 옥외 폭로 시험 등이 있다. 그러나 이러한 시험들은 그 시험 방법에 따라서 정량적인 평가에 한계가 있음은 물론 장기간 소요되는 등 곤란한 문제점이 있다. 그러므로 선박 및 해양구조물을 비롯하여 교량, 각종 강 구조물의 도장 방식에 사용되는 방식용 도료의 성능을 단기간에 적절하게 평가할 수 있는 가속시험법이 제시되며 연구-사용되고 있다. 그 중 도막 방식 성능을 보다 효율적, 비파괴적, 정량적으로 평가할 수 있는 임피던스 분광법(EIS)과 같은 전기화학적 방법은 상대적으로 시험 기간을 크게 단축시킬 수 있고, 대상 방식 도장의 미세한 성능 차이도 분별 가능하다는 장점이 있다[1]. 따라서 본 연구에서는 선박 및 해양구조물 등 가혹한 부식환경에서 강력한 내구성을 가질 수 있도록 다양한 종류의 표면처리 도장 시편을 제작하여 자외선 조사-염수분무-침지환경 등의 열악한 환경조건 하에서 부식-열화 촉진 시험을 실시하였다. 그리고 그 촉진 열화 과정에서 도막의 외관 상태를 관찰 분석함은 물론 전기화학적 임피던스 분광법을 병행 측정하며 그 표면막의 부식 및 도막 열화도를 비교-종합 평가하였다.본 연구에 사용된 시편은 Al 및 Zn 도금 강판에 에폭시, 에폭시-실리콘 우레탄, 에폭시-우레탄 도장 시편으로 Scribe, No Scribe 및 비교재 Al 및 Zn 도금 시편으로 분류하여 각각 실험을 진행하였다. 즉, 도막 열화 시험은 복합 노화 시험법으로 UV 조사 36 시간(ASTM G53), 염수분무 32 시간(ISO 7253), 수분 응축 10 시간을 1 Cycle로 100 Cycle(7800 시간) 동안 실험을 진행하였다. 이때 도막 열화도 평가는 전기화학적 임피던스 분광법을 이용하여 각 실험 조건별로 주파수에 따른 임피던스(Z) 값을 평가하였다. 즉, 상온 $25^{\circ}C$의 3.5% NaCl 100 ml 수용액에 작동 전극(Working Electrode)과 구리 도선을 통해 연결하였고, 노출 면적은 $1cm^2$로 일정하게 유지 하였으며, 상대 전극(Counter Electrode)은 탄소봉, 기준 전극(Reference Electrode)으로 포화카로멜전극(Saturated Calomel Electrode)을 사용하여 측정하였다. No Scribe 시편의 경우에는 Al 기판 에폭시-실리콘 우레탄 도장 시편이 우수한 도막 저항성을 나타내었으며, 에폭시-우레탄 도장시편은 23사이클 이후의 저항값이 가장 낮게 나타났다. Zn 기판의 경우는 에폭시, 에폭시-실리콘 우레탄, 에폭시-우레탄 도장 시편 모두 저항 값이 유사하였으며, Al 및 Zn 도금 시편은 도장 처리된 시편에 비해 훨씬 낮은 저항 값을 보였다. 또한 Scribe 시편의 경우에는 Al 기판 에폭시-실리콘 우레탄 도장 시편에서 높은 초기 저항 값을 보였으며, 23 사이클 후의 저항 값은 세 종류의 도막에서 약 1~0.1 Gohm 으로 나타났다. 그리고 Zn 기판 에폭시-실리콘 우레탄 도장 시편에서 가장 낮은 도막 저항 값이 나타났다. 이상의 실험을 통해서 본 연구 내용은 실내촉진시험으로 선박 및 해양 강 구조물에 사용되는 다양한 종류의 도막의 열화도를 평가하는 기초 설계 지침으로 응용될 수 있을 것으로 사료된다. 한편, 도막은 노출 환경에 따라 방식 성능이 다르므로 실제 도막의 사용환경을 고려하여 도장 사양별 적용 부위에 따른 적정 가속 실험 방법을 선정할 필요가 있다고 사료된다.

  • PDF

A Formulated Korean Red Ginseng Extract Inhibited Nitric Oxide Production through Akt- and Mitogen Activated Protein Kinase-dependent Heme Oxygenase-1 Upregulation in Lipoteichoic Acid-stimulated Microglial Cells (홍삼추출액은 lipoteichoic acid로 자극된 소교세포에서 Akt 및 MAPK 의존적으로 heme oxygenase-1 발현을 유도함으로써 NO 생성을 억제함)

  • Shin, Ji Eun;Lee, Kyungmin;Kim, Ji-Hee;Madhi, Iskander;Kim, YoungHee
    • Journal of Life Science
    • /
    • v.29 no.4
    • /
    • pp.402-409
    • /
    • 2019
  • Korean red ginseng made from steaming and drying fresh ginseng has long been used as a traditional herbal medicine due to its effects on the immune, endocrine, and central nerve systems and its anti-inflammatory activity. In this study, we investigated the molecular mechanism responsible for the anti-inflammatory effects of a formulated Korean red ginseng extract (RGE) in response to lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria. RGE inhibited LTA-induced nitric oxide (NO) secretion and inducible nitric oxide synthase (iNOS) expression in BV-2 microglial cells, without affecting cell viability. RGE also inhibited nuclear translocation of nuclear factor kappa B ($NF-{\kappa}B$) p65 and degradation of $I{\kappa}B-{\alpha}$. In addition, RGE increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner, and the inhibitory effect of RGE on iNOS expression was abrogated by small interfering RNA-mediated knockdown of HO-1. Moreover, RGE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Furthermore, the phosphoinositide-3-kinase (PI-3K) inhibitor and mitogen-activated protein kinase (MAPK) inhibitors suppressed RGE-mediated expression of HO-1, and RGE enhanced the phosphorylation of Akt, extracellular signal-regulated kinases (ERKs), p38, and c-JUN N-terminal kinases (JNKs). These results suggested that RGE suppressed the production of NO, a proinflammatory mediator, by inducing HO-1 expression via PI-3K/Akt- and MAPK-dependent signaling in LTA-stimulated microglia. The findings indicate that RGE could be used for the treatment of neuroinflammation induced by grampositive bacteria and that it may have therapeutic potential for various neuroinflammation-associated disorders.