• Title/Summary/Keyword: ${\alpha}-Factor$

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Role of E2F1 in Endoplasmic Reticulum Stress Signaling

  • Park, Kyung Mi;Kim, Dong Joon;Paik, Sang Gi;Kim, Soo Jung;Yeom, Young Il
    • Molecules and Cells
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    • v.21 no.3
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    • pp.356-359
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    • 2006
  • The transcription factor E2F1 coordinates cell cycle progression and induces apoptosis in response to DNA damage stress. Aside from DNA damage, the role of E2F1 in the endoplasmic reticulum (ER) stress signaling pathways is unclear. We found that $E2F1^{-/-}$ murine embryonic fibroblasts (MEFs) are resistant to apoptosis triggered by the ER stress inducer thapsigargin. In addition, E2F1 deficiency results in enhanced phosphorylation of eukaryotic translation initiation factor $2{\alpha}$ ($elF2{\alpha}$). These results therefore indicate that E2F1 deficiency increases phosphorylation of $elF2{\alpha}$ in response to ER stress triggered by thapsigargin, and suggest that the reduction in ER stress-induced apoptosis in E2F1-deficient cells is related to the high level of $elF2{\alpha}$ phosphorylation.

Anti-inflammatory Effects of Saussurea Lappa Extracts in Murine Macrophages (설치류 대식세포에서 목향(木香) 추출물의 항염증 효과)

  • Lee, Min-Suk;Ryu, Do-Gon;Kwon, Kang-Beom
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.2
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    • pp.275-279
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    • 2011
  • In order to validate the use of Saussurea Lappa as an anti-inflammatory drug in the traditional Korean medicine, I have investigated the effects of water-soluble extract of Saussurea Lappa (ESL) on the production of pro-inflammatory tumor necrosis factor-alpha (TNF-${\alpha}$) in murine RAW 264.7 macrophages stimulated with the endotoxin lipopolysaccharide (LPS). The extract inhibited dose-dependently TNF-${\alpha}$ production without its cytotoxic effect on the macrophages, as measured by enzyme-linked immunosorbent assay, and significantly decreased mRNA levels of TNF-${\alpha}$, as determined using reverse transcription polymerase chain reaction. The extract also inhibited LPS-induced activation of nuclear factor-${\kappa}B$, thereby resulting in TNF-${\alpha}$ gene expression. These results suggest that ESL may have therapeutic potential in the control of inflammatory diseases mediated by activated macrophages.

Psychometric Testing of the Korean Version of Templer's Death Anxiety Scale among Older Adults (노인 대상 한국형 Templer의 죽음불안도구 신뢰도 및 타당도)

  • Hwang, Hyenam
    • Journal of East-West Nursing Research
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    • v.25 no.1
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    • pp.26-32
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    • 2019
  • Purpose: The purpose of this methodological study was to examine the validity and reliability of a translated Korean version of Templer's death anxiety scale among older adults. Methods: The translated Korean scale was administered to 203 older people who aged over 65 years. Exploratory factor analysis was utilized to assess the factor structure of the scale. Internal consistency of the scale was determined using Cronbach's ${\alpha}$ and Guttman's split-half coefficient. Results: Factor loadings of the scale ranged from .43 to .86. The scale showed good internal consistencies of both total scale (13 items, ${\alpha}=.83$) and three sub-scales: meaning of death (6 items, ${\alpha}=.77$), death-related event (5 items, ${\alpha}=.72$), and time of death (2 items, ${\alpha}=.80$). The concurrent validity compare with Fear of Death Scale was significant. The Cronbach's alpha and Guttman's split-half coefficient were .83 and .80, respectively. Conclusion: The findings of this study demonstrate that the Korean version of Templer's death anxiety scale had satisfactory validity and reliability to measure death anxiety among Korean older people.

Expression of Hypoxia-inducible Factor-$1{\alpha}$ in Non-small Cell Lung Cancer: Relationship to Prognosis and Tumor Biomarkers (비소세포 폐암에서 HIF-$1{\alpha}$의 발현: 예후 및 종양표지자와의 관련성)

  • Cho, Sung-Rae;Byun, Joung-Hun;Kim, Jong-In;Lee, Bong-Geun;Chun, Bong-Kwon
    • Journal of Chest Surgery
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    • v.39 no.11 s.268
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    • pp.828-837
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    • 2006
  • Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

CaMKII Inhibitor KN-62 Blunts Tumor Response to Hypoxia by Inhibiting HIF-$1{\alpha}$ in Hepatoma Cells

  • Lee, Kyoung-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.5
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    • pp.331-336
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    • 2010
  • In rapidly growing tumors, hypoxia commonly develops due to the imbalance between $O_2$ consumption and supply. Hypoxia Inducible Factor (HIF)-$1{\alpha}$ is a transcription factor responsible for tumor growth and angiogenesis in the hypoxic microenvironment; thus, its inhibition is regarded as a promising strategy for cancer therapy. Given that CamKII or PARP inhibitors are emerging anticancer agents, we investigated if they have the potential to be developed as new HIF-$1{\alpha}$-targeting drugs. When treating various cancer cells with the inhibitors, we found that a CamKII inhibitor, KN-62, effectively suppressed HIF-$1{\alpha}$ specifically in hepatoma cells. To examine the effect of KN-62 on HIF-$1{\alpha}$-driven gene expression, we analyzed the EPO-enhancer reporter activity and mRNA levels of HIF-$1{\alpha}$ downstream genes, such as EPO, LOX and CA9. Both the reporter activity and the mRNA expression were repressed by KN-62. We also found that KN-62 suppressed HIF-$1{\alpha}$ by impairing synthesis of HIF-$1{\alpha}$ protein. Based on these results, we propose that KN-62 is a candidate as a HIF-$1{\alpha}$-targeting anticancer agent.

The Effects of Chelidonium majus on NO and $TNF-{\alpha}$ Production in Macrophages (백굴채가 대식세포의 NO 및 $TNF-{\alpha}$ 생성에 미치는 영향)

  • 김홍준;문석재;김동웅;문구;원경숙;윤준철;김유경;원진희
    • The Journal of Korean Medicine
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    • v.24 no.2
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    • pp.138-147
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    • 2003
  • Objectives : In this study, we investigated the mechanism by which Chelidonium majus (CM) regulates nitric oxide (NO) production. Methods : Using mouse peritoneal macrophages, the mechanism by which CM regulates NO or tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ production was examined. NO release was measured by the Griess method. $TNF-{\alpha}$ production was measured by the ELISA method. The protein extracts were prepared and samples were analyzed for the inducible NOS(iNOS) expression and nuclear factor kappa $B(NF-{\kappa}B)$ activation by Western blotting. Results : When CM was used in combination with recombinant $interferon-{\gamma}{\;}(rIFN-{\gamma})$, there was a marked cooperative induction of NO production. CM had an effect on NO production by itself. The expression of the iNOS gene was increased in $rIFN-{\gamma}$ plus CM-stimulated peritoneal macrophages and almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of $NF-{\kappa}B$. The $NF-{\kappa}B$ activation was increased in rIFN-{\gamma} plus CM-induced peritoneal macrophages. The increased production of NO from $rIFN-{\gamma}$ plus CM-stimulated peritoneal rnacrophages was decreased by the treatment with $N^{G}-monomethyl-{_L}-arginine{\;}(N^{G}MMA){\;}N^{\alpha}-Tosyl-Phe$ chloromethyl ketone (TPCK) , and was almost completely inhibited by pre-treatment with PDTC. Furthermore, treatment with CM alone or rIFN-{\gamma} plus CM in peritoneal macrophages caused a significant increase in $TNF-{\alpha}$ production. PDTC decreased CM-induced $TNF-{\alpha}$ production significantly. After CM treatment in HT-29 or AGS cells, cell viability decreased. Conclusions : These findings demonstrate that CM increases the production of NO and $TNF-{\alpha}{\;}by{\;}rIFN-{\gamma}-primed$ macrophages and suggest that NF-B plays a critical role in mediating these effects of CM.

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A Study on the Application of a Wind Power Generation System Using Outdoor Air on the Rooftop and Indoor Ventilation (건물 옥상외기와 실내배기를 활용한 풍력발전시스템 적용 연구)

  • Lee, Yong-Ho;Park, Jin-Chul;Hwang, Jung-Ha
    • Journal of the Korean Solar Energy Society
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    • v.34 no.1
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    • pp.72-80
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    • 2014
  • This study proposed a wind power generation system utilizing outdoor air on the rooftop and indoor ventilation, which would increase according to the building height, as a way to help to save energy consumption in a building by using wind power energy of the new renewable energy sources. The study measured the distribution of air currents and power generation according to the usage factor of exhaust pipes in the kitchen and bathroom and identified the elements to consider when applying a wind power generation system to buildings in order to use outdoor air on the rooftop increasing according to the height and the indoor ventilation produced in the facility vertical shafts inside the buildings by installing a wind power generation system on the rooftop. (1) The study measured the ventilation velocity of the kitchen hood and bathroom ventilation fan by changing the zone areas by the households according to the usage factor of [${\alpha}$]=33~100%. As a result, the kitchen ventilation pipe generated the ventilation wind of 3.0m/s or more at the usage factor of [${\alpha}$] 66% or higher, and the bathroom ventilation pipe generated ventilation velocity lower than 3.0m/s, the blade velocity of the wind power generator, even after the usage factor rose to [${\alpha}$]=100%. (2) As the old bathroom ventilation pipe generated the ventilation velocity of 3.0m/s, the blade velocity of the wind power generator, even with the rising usage factor [${\alpha}$], the application of an outdoor air induction module increased the ventilation velocity by 2.9m/s at the usage factor of [${\alpha}$]=33%, 3.8m/s at the usage factor of [${\alpha}$]=66%, and 3.6m/s at the usage factor of [${\alpha}$]=100%. Thus the ventilation velocity of 3.0m/s, the blade velocity of the wind power generator, or higher was secured. (3) The findings prove that the applicability of a wind power generation system using outdoor air on the rooftop and indoor ventilation is excellent, which raises a need for various efforts to increase the possibility of its commercialization such as securing its structural stability according to momentary gusts on the rooftop and typhoons in summer and making the structure light to react to the wind directions of outdoor air on the rooftop according to the seasons.

Xanthium strumarium suppresses degranulation and pro-inflammatory cytokines secretion on the mast cells (비만세포에서의 창이자의 탈과립 및 pro-inflammatory cytokines 분비량에 미치는 영향)

  • Lyu, Ji-Hyo;Yoon, Hwa-Jung;Hong, Sang-Hoon;Ko, Woo-Shin
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.21 no.3
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    • pp.82-93
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    • 2008
  • Objective: Previously, the methanol extracts of the semen of Xanthium strumsrium could involved anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated Raw 264,7 cells, We evaluated the anti-allergic effects of X. strumarium on rat basophilic leukemia (RBL-2H3) cells, Methodes : To investigate the effect of X. strumarium on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced RBL-2H3 cells. The effects of X. strumarium on the degranulation and the pro-inflammatory cytokines secretion and expression from RBL-2H3 cells were evaluated with $\beta$-hexosaminidase assay, ELISA, and RT-PCR analysis, In addition, we examined the effects of X. strumarium on nuclear factor (NF)-${\kappa}B$ activation and $I{\kappa}B-\alpha$ degradation using Western blot analysis. Results : X. strumarium inhibited degranulation and secretions and expressions of pro-inflammatory cytokines, such as tumor necrosis factor-alpha ($TNF-\alpha$), interleukin (IL)-4 and cyclooxygenase (COX)-2, on stimulated RBL-2H3 cells, however, X. strumarium not affect cell viability. In stimulated RBL-2H3 cells, the protein expression level of nuclear factor-kappa B (NF-${\kappa}B$) was decreased in the nucleus by X. strumarium. In addition, X. strumarium suppressed the degradation of inhibitory protein $I{\kappa}B-{\alpha}$ protein in RBL-2H3 cells. Conclusion : These results suggest that X. strumarium inhibits the degranulation and secretion of pro-inflammatory cytokines through blockade of NF-${\kappa}B$ activation and I $I{\kappa}B-{\alpha}$ degradation.

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Sequential changes of Interleukin-6, Tumor Necrosis Factor-$\alpha$, and Troponin-T During Open Heart Surgery with Cardiopulmonary Bypass (체외순환을 이용한 심장수술시 혈청 Interleukin-6, Tumor Necrosis Factor-$\alpha$와 Troponin-T의 시간대별 변화)

  • 류지윤;최석철;곽기오;최국렬;김송명;조광현
    • Journal of Chest Surgery
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    • v.32 no.11
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    • pp.971-977
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    • 1999
  • Background: Immunologic and inflammatory responses of cardiopulmonary bypass(CPB) influence postoperative mortality and morbidity with multiple organ injury. It has been reported that ischemia/reperfusion induced-myocardial injury during CPB is causative of release of inflammatory cytokines such as interleukin-6(IL-6) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The purpose of this study was to detect the time course of the activated cytokine and troponin-T(TnT), and to examine the correlation between such parameters during CPB. Material and Method: The serial samples were collected from arterial blood via radial arterial catheter in 23 patients who are underwent open heart surgery (OHS) with CPB, the IL-6, TNF-$\alpha$ and TnT were checked. Result: \circled1 IL-6, TNF$\alpha$- and TnT concentration increased significantly during CPB with a peaking level of CPB-off (p 0.05). \circled2 IL-6 had highly positive correlation with aortic cross clamping time and total bypass time(r=0.80, 0.78; p 0.05, respectively). \circled3 There was no correlation among IL-6, TNF-$\alpha$ and TnT. Conclusion: In conclusion, these data showed that elevated production of serum IL-6 during CPB was attributable to ischemia/reperfusion induced-myocardial damage. IL-6 will become a new and sensitive biological marker in assessment of myocardial damage during OHS with CPB. However, further studies will be needed to apply IL-6 in more patient population.

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A Strong Transcription Activity of the Bombyx mori Elongation Factor 1α Promoter

  • Goo, Tae-Won;Kim, Sung-Wan;Kim, Seong-Ryul;Park, Seung-Won;Kang, Seok-Woo;Choi, Kwang-Ho;Yun, Eun-Young
    • International Journal of Industrial Entomology and Biomaterials
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    • v.24 no.2
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    • pp.49-55
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    • 2012
  • We previously isolated 9 clones that show stronger signal compared to B. mori cytoplasmic actin gene (BmA3) by using a dot blot hybridization. In this study, we focused on one clone among these clones which has high amino acid homology with elongation factor ${\alpha}$ gene of B. mori. This clone, named $bEF1{\alpha}$ (B. mori elongation factor ${\alpha}$) was ubiquitously expressed in all tissues and developmental stage of B. mori. As result of promoter assay using dual luciferase assay system, we found the highest transcription activity region (-702/+38) in the 5'-flanking region of $bEF1{\alpha}$ gene, which has about 20 fold more intensive promoter activity than BmA3 promoter. Moreover, the $bEF1{\alpha}$ promoter was normally regulated in Bm5, Sf9, and S2 cells. Therefore, we suggest that $bEF1{\alpha}$ promoter may be used more powerful and effectively for transgene expression in various insects containing B. mori as a universal promoter.