• Title/Summary/Keyword: activation factor

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Role of PI3-Kinase/Akt Pathway in the Activation of Etoposide-Induced $NF-{\kappa}B$ Transcription Factor

  • Choi Yong-Seok;Park Heon-Yong;Jeong Sun-Joo
    • Journal of Microbiology and Biotechnology
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    • v.16 no.3
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    • pp.391-398
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    • 2006
  • $NF-{\kappa}B$ is a transcription factor involved in the innate immunity against bacterial infection and inflammation. It is also known to render cells resistant to the apoptosis caused by some anticancer drugs. Such a chemoresistance of cancer cells may be related to the activation of $NF-{\kappa}B$ transcription factor; however, the mechanism of activation is not well understood. Here, we demonstrate that a chemotherapeutic agent, etoposide, independently stimulates the $I{\kappa}B{\alpha}$ degradation pathway and PI3-kinase/Akt signaling pathway: The classical $I{\kappa}B{\alpha}$ degradation pathway leads to the nuclear translocation and DNA binding of p65 subunit through $IKK{\beta}$ kinase, whereas the PI3-kinase/Akt pathway plays a distinct role in activating this transcription factor. The PI3-kinase/Akt pathway acts on the p50 subunit of the $NF-{\kappa}B$ transcription factor and enhances the DNA binding affinity of the p50 protein. It may also explain the role of the PI3-kinase/Akt pathway in the anti-apoptotic function of $NF-{\kappa}B$ during chemoresistance of cancer cells.

Nrf2 in TIME: The Emerging Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Tumor Immune Microenvironment

  • Jialin Feng;Oliver J. Read;Albena T. Dinkova-Kostova
    • Molecules and Cells
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    • v.46 no.3
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    • pp.142-152
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    • 2023
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.

Effect of Particle Size on Thermal Property of RDX and HMX (HMX와 RDX의 열적 특성에 미치는 입자 크기의 영향)

  • Kim, Seung Hee
    • Applied Chemistry for Engineering
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    • v.23 no.3
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    • pp.352-357
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    • 2012
  • Techniques of thermal analyses such as DSC and TGA have been used in the study of activation energy (Ea) and frequency factor (A) depending on the particle size of RDX and HMX. Activation energy and frequency factor were calculated by Kissinger's method and Vyazovkin's method. As the particle size of RDX increased, TGA showed activation energy increased, but DSC didn't show. However, In case of HMX, as the particle size increased, both of DSC and TGA showed increase in activation energy. Moreover, Vyazovkin's method can obtain activation energy and mechanism according to decomposition of RDX and HMX.

A study on the Plan for Organization Activation use analysis of Success factor Integration Information System (통합정보시스템 구축 프로젝트 성공 요인 분석을 통한 조직 활성화 방안에 대한 연구)

  • Park, Jong-Ki;Kang, Kyong-Sik
    • Proceedings of the Safety Management and Science Conference
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    • 2006.11a
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    • pp.367-372
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    • 2006
  • Since 1990's, many enterprises have constructed Integration Information System. Especially, they want to become an advanced company use ERP package. Already, ERP system come to high level which is stabilized and support independent business process of many industry sectors. Therefore, important success factors for ERP project are change management and organization activation. Although most companies had previous good plans, but those are not satisfied. Because of failed to change management and discontinued next activity for promotion. This paper studied success factors of project team and plan for organization activation. Also, it proposed next study subject about investigate the role of the member of task force team as a factor that makes the ERP system a success. The results of this study can be used for a successful construction of the ERP system as a solution about internal problems of Project team.

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A study on the Plan for Organization Activation use analysis of Success factor Integration Information System (통합정보시스템 구축 프로젝트 성공 요인 분석을 통한 조직 활성화 방안에 대한 연구)

  • Park, Jong-Ki;Kang, Kyong-Sik
    • Journal of the Korea Safety Management & Science
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    • v.8 no.5
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    • pp.231-242
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    • 2006
  • Since 1990's, many enterprises have constructed Integration Information System. Especially, they want to become an advanced company use ERP package. Already, ERP system come to high level which is stabilized and support independent business process of many industry sectors. Therefore, important success factors for ERP project are change management and organization activation. Although most companies had previous good plans, but those are not satisfied. Because of failed to change management and discontinued next activity for promotion. This paper studied success factors of project team and plan for organization activation. Also, it proposed next study subject about investigate the role of the member of task force team as a factor that makes the ERP system a success. The results of this study can be used for a successful construction of the ERP system as a solution about Internal problems of Project team.

Suppression of the TRIF-dependent Signaling Pathway of Toll-like Receptor by Cadmium in RAW264.7 Macrophages

  • Park, Se-Jeong;Youn, Hyung-Sun
    • Molecular & Cellular Toxicology
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    • v.5 no.3
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    • pp.187-192
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    • 2009
  • Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens. The stimulation of TLRs by microbial components triggers the activation of the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-$\beta$ (TRIF)-dependent downstream signaling pathways. TLR/MyD88 signaling pathway induces the activation of nuclear factor-kappa B (NF-${\kappa}B$) and the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-$1{\beta}$. On the other hand, TLR/TRIF signaling pathway induces the delayed-activation of NF-${\kappa}B$ and interferon regulatory factor 3 (IRF3), and the expression of type I interferons (IFNs) and IFN-inducible genes. The divalent heavy metal cadmium (Cd) is clearly toxic to most mammalian organ systems, especially the immune system. Yet, the underlying toxic mechanism(s) remain unclear. Cd inhibits the MyD88-dependent pathway by ceasing the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether Cd inhibits the TRIF-dependent pathway. Presently, Cd inhibited NF-${\kappa}B$ and IRF3 activation induced by lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid. Cd inhibited LPS-induced IRF3 phosphorylation and IFN-inducible genes such as interferon inducible protein-10 and regulated on activation normal T-cell expressed and secreted (RANTES). These results suggest that Cd can modulate TRIF-dependent signaling pathways of TLRs.

Chromatin-remodeling Factor INI1/hSNF5/BAF47 Is Involved in Activation of the Colony Stimulating Factor 1 Promoter

  • Pan, Xuefang;Song, Zhaoxia;Zhai, Lei;Li, Xiaoyun;Zeng, Xianlu
    • Molecules and Cells
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    • v.20 no.2
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    • pp.183-188
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    • 2005
  • INI1/hSNF5/BAF47 is a core component of the hSWI/ SNF ATP-dependent chromatin remodeling complex, and it has been implicated in regulating gene expression, cell division and tumorigenesis. We investigated whether INI1/hSNF5/BAF47 functions in activation of the colony stimulating factor 1 (CSF1) promoter in HeLa cells. Overexpression of INI1/hSNF5/BAF47 promoted CSF1 transcription, and siRNA targeting INI1/hSNF5/ BAF47 (siINI1) strongly inhibited the activity of the CSF1 promoter. We demonstrated that all conserved domains of INI1/hSNF5/BAF47 are needed for CSF1 transcription. ChIP experiment showed that INI1/ hSNF5/BAF47 is recruited to the region of the CSF1 promoter. Taken together, these results indicate that INI1/hSNF5/BAF47 is involved in activation of the CSF1 promoter.

Ghrelin Protects Spinal Cord Motoneurons Against Chronic Glutamate Excitotoxicity by Inhibiting Microglial Activation

  • Lee, Sung-Youb;Kim, Yu-Mi;Li, Endan;Park, Seung-Joon
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.1
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    • pp.43-48
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    • 2012
  • Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin protects motoneurons against chronic glutamate excitotoxicity through the activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-$3{\beta}$ pathways. Previous studies suggest that activated microglia actively participate in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown whether ghrelin exerts its protective effect on motoneurons via inhibition of microglial activation. In this study, we investigate organotypic spinal cord cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron death, and treatment of ghrelin significantly attenuated THA-induced motoneuron loss, as previously reported. Ghrelin prevented THA-induced microglial activation in the spinal cord and the expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$. Our data indicate that ghrelin may act as a survival factor for motoneurons by functioning as a microglia-deactivating factor and suggest that ghrelin may have therapeutic potential for the treatment of ALS and other neurodegenerative disorders where inflammatory responses play a critical role.

The Reliability and Validity of the Korean Version of Behavioral Activation for Depression Scale (한글판 행동활성화 척도의 신뢰도와 타당도)

  • Oh, Ji-Hye;Hwang, Na-Ri;Cha, Yun-Ji;Lee, Eun-Byeol;Choi, Kee-Hong;Seo, Ho-Jun
    • Journal of Korean Neuropsychiatric Association
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    • v.56 no.2
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    • pp.89-97
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    • 2017
  • Objectives The Behavioral Activation of Depression Scale (BADS) has been reported to be a valid tool for assessing the different behavioral aspects of depression, such as activation, rumination or avoidance, and functional impairment. The aim of this study was to assess the reliability and validity of the Korean version of BADS (K-BADS). Methods A sample of 196 outpatients completed the K-BADS and the data were analyzed for internal consistency and factor structures. An additional 51 outpatients re-filled the K-BADS after two weeks for the test-retest reliability. To test for the validity, the Hospital Anxiety and Depression Scale (HADS), Working Alliance Inventory (WAI), Drug Attitude Inventory-10 (DAI-10), and Mindfulness Attention Awareness Scale (MAAS) were administered. Results Internal consistency of K-BADS was good (Cronbach's alpha=0.843) and principal component factor analysis revealed the four-factor structure. The K-BADS showed a reasonable test-retest reliability (r=0.863, p<0.001). The total score of K-BADS correlated significantly with the total scores of the HADS depression (r=-0.694) and HADS anxiety (r=-0.681). No correlations were found between the K-BADS and the K-WAI (r=0.170) and between the K-BADS and the K-DAI-10 (r=0.311). Conclusion The K-BADS is a reliable and valid instrument for measuring the behavioral activation for depression in Korean patients with depressive symptoms.

Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells

  • Joo, Donghyun;Woo, Jong Soo;Cho, Kwang-Hyun;Han, Seung Hyun;Min, Tae Sun;Yang, Deok-Chun;Yun, Cheol-Heui
    • BMB Reports
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    • v.49 no.4
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    • pp.220-225
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    • 2016
  • Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling.